%0 journal article %@ 0934-0866 %A Störmann, F., Roch, T., Lendlein, A., Wischke, C. %D 2024 %J Particle & Particle Systems Characterization %R doi:10.1002/ppsc.202300099 %T Microfluidic templating and initiator-free photocrosslinking of protein-loaded PCL microcapsules %U https://doi.org/10.1002/ppsc.202300099 %X Polymer network materials are interesting alternatives to thermoplastic polymers. Here, the preparation of polymer capsules is investigated, which are made from poly(ε-caprolactone) (PCL) networks and are compartmentalized in a crosslinked PCL shell and a core that is suitable to enclose payloads of interest. Aided by microfluidic templating, PCL network capsules with a narrow size distribution (176 ± 5 µm) and thin shells (≈7.5 µm) are formed from 4-arm star-shaped 12 kDa PCL precursors by photoinitiator-free UV light-induced radical polymerization of methacrylate end-groups. FITC-BSA is encapsulated as a model protein. The physicochemical characterization of the capsules indicated a partial crosslinking of methacrylate endgroups into netpoints. Microscopy revealed a fraction of collapsed capsules that are discussed in the context of network stability and mechanical stress created at the capsule interfaces during solvent removal. The incubation of particles with human embryonic kidney (HEK) cells showed good cell compatibility, suggesting their potential use in biosciences and beyond. %0 conference poster %@ %A Wischke, C. %D 2023 %J Freiburg Macromolecular Colloquium 2023 %T Inspired by material fatigue: On-demand release systems %U %X %0 journal article %@ 1422-0067 %A Seifert, B., Baudis, S., Wischke, C. %D 2023 %J International Journal of Molecular Sciences %N 22 %P 16390 %R doi:10.3390/ijms242216390 %T Composition dependent protein-material interaction of poly(methyl methacrylate-co-styrene) nanoparticle series %U https://doi.org/10.3390/ijms242216390 22 %X Polymer nanoparticles continue to be of high interest in life science applications. Still, adsorption processes occurring in protein-containing media and their implications for biological responses are not generally predictable. Here, the effect of nanoparticle composition on the adsorption of bovine serum albumin (BSA), fibronectin (FN) and immunoglobulin G (IgG) as structurally and functionally different model proteins was explored by systematically altering the composition of poly(methyl methacrylate-co-styrene) nanoparticles with sizes in a range of about 550 nm. As determined by protein depletion from the suspension medium via a colorimetric assay, BSA and IgG adsorbed at similar quantities, while FN reached larger masses of adsorbed protein (up to 0.4 ± 0.06 µg·cm−2 BSA, 0.42 ± 0.09 µg·cm−2 IgG, 0.72 ± 0.04 µg·cm−2 FN). A higher content of styrene as the more hydrophobic polymer component enhanced protein binding, which suggests a contribution of hydrophobic interactions despite the particles exhibiting strongly negatively charged surfaces with zeta potentials of −44 to −52 mV. The quantities of adsorbed proteins were estimated to correspond to a confluent surface coverage. Overall, this study illustrated how protein binding can be controlled by systematically varying the nanoparticle bulk composition and may serve as a basis for establishing interfaces with a targeted level of protein retention and/or presentation. %0 journal article %@ 1999-4923 %A Altabal, O., Wischke, C., Lendlein, A. %D 2022 %J Pharmaceutics %N 12 %P 2611 %R doi:10.3390/pharmaceutics14122611 %T Design of Reservoirs Enabling Stress-Induced Sequential Release Systems %U https://doi.org/10.3390/pharmaceutics14122611 12 %X Mechanical stress is recognized as a principle for opening enclosed compartments through compression, stretching, or shear, eventually resulting in the onset of a diffusion-controlled release. Here, we hypothesized that the geometrical design of cavities (cut-outs) introduced as containers in elastic polymer substrates and sealed with a brittle coating layer would enable a pre-defined release of different compounds by stress concentration phenomena. Design criteria such as cut-out shapes, orientations, and depths were initially assessed for suitably different stress concentrations in computational models. In substrates fabricated from polydimethylsiloxane by photolithographic techniques, the local strains at horizontal rectangular, circular, and vertical rhombus-shaped cut-outs systematically increased under horizontal stretching as proposed. When filled with model compounds and coated with poly(n-butyl cyanoacrylate), a pre-defined induced breakage of the coating and compound release was confirmed upon continuous uniaxial stretching. This proof of concept demonstrates how device design and functions interlink and may motivate further exploration in technology and medicine for deformation-induced on-demand dosage applications. %0 journal article %@ 2073-4360 %A Altabal, O., Wischke, C. %D 2022 %J Polymers %N 22 %P 4863 %R doi:10.3390/polym14224863 %T Analyzing the Mechanical Properties of Free-Standing PACA Thin Films Using Microindentation Technique %U https://doi.org/10.3390/polym14224863 22 %X Assessing the mechanical properties of materials is of fundamental relevance for their rational usage, but can be challenging with standard tensile testing for highly brittle polymers used, e.g., as coatings. Here, a procedure for the mechanical analysis of free-standing poly(alkyl cyanoacrylate) (PACA) films using microindentation has been explored. Rigid and transparent films from PACA with various side chain compositions were formed on top of square polymer frames by in situ polymerization. Under microscopic control, the free-standing films were analyzed using a microelectromechanical sensing system. By this procedure, decreasing Young’s moduli E for increasing PACA side chain length and flexibility were determined with strain at break εB between 0.36% for poly(ethyl cyanoacrylate) and 4.6% for poly(methoxyethyl cyanoacrylate). Based on this successful application, the applied methodology may be relevant for characterizing various coating materials, which are otherwise hard to form as thin free-standing films, and using the data, e.g., in computationally assisted design and evaluation of hybrid material devices. %0 journal article %@ 1999-4923 %A Tuncaboylu, D.C., Wischke, C. %D 2022 %J Pharmaceutics %N 11 %P 2331 %R doi:10.3390/pharmaceutics14112331 %T Opportunities and Challenges of Switchable Materials for Pharmaceutical Use %U https://doi.org/10.3390/pharmaceutics14112331 11 %X Switchable polymeric materials, which can respond to triggering signals through changes in their properties, have become a major research focus for parenteral controlled delivery systems. They may enable externally induced drug release or delivery that is adaptive to in vivo stimuli. Despite the promise of new functionalities using switchable materials, several of these concepts may need to face challenges associated with clinical use. Accordingly, this review provides an overview of various types of switchable polymers responsive to different types of stimuli and addresses opportunities and challenges that may arise from their application in biomedicine. %0 journal article %@ 2073-4360 %A Wischke, C., Hofmann, D. %D 2022 %J Polymers %N 18 %P 3762 %R doi:10.3390/polym14183762 %T Predictive Shapes of Ellipsoid PPDL-PTHF Copolymer Particles Prepared by the Phantom Stretching Technique %U https://doi.org/10.3390/polym14183762 18 %X Ellipsoidal polymer particles can be prepared from spheres by unidirectional stretching at elevated temperatures, while the particles’ aspect ratios (AR) that result from this phantom stretching methodology are often not precisely predictable. Here, an elastic deformation model was exemplarily evaluated for ~50 µm spherical microparticles from PPDL-PTHF block copolymers. The prolate ellipsoidal particles, obtained by stretching in polyvinyl alcohol phantoms, differed in dimensions at identical relative phantoms elongations up to 150%, depending on the relative polymer composition and their systematically altered mechanical properties. Importantly, the resulting particle shapes within the studied range of AR up to ~4 matched the predictions of the elastic deformation model, which includes information of the elastic moduli of phantom and particle materials. These data suggest that the model may be applicable to predict the conditions needed to precisely prepare ellipsoids of desired AR and may be applicable to various deformable particle materials. %0 journal article %@ 0884-2914 %A Friess, F., Lendlein, A., Wischke, C. %D 2021 %J Journal of Materials Research %P 3248-3257 %R doi:10.1557/s43578-021-00295-2 %T Size control of shape switchable micronetworks by fast two-step microfluidic templating %U https://doi.org/10.1557/s43578-021-00295-2 %X Shape-memory polymer micronetworks (MN) are micrometer-sized objects that can switch their outer shape upon external command. This study aims to scale MN sizes to the low micrometer range at very narrow size distributions. In a two-step microfluidic strategy, the specific design of coaxial class capillary devices allowed stabilizing the thread of the dispersed phase to efficiently produce precursor particles in the tip-streaming regime at rates up to ~ 170 kHz and final sizes down to 4 µm. In a subsequent melt-based microfluidic photocrosslinking of the methacrylate-functionalized oligo(ɛ-caprolactone) precursor material, MN could be produced without particle aggregation. A comprehensive analysis of MN properties illustrated successful crosslinking, semi-crystalline morphology, and a shape-switching functionality for all investigated MN sizes (4, 6, 9, 12, 22 µm). Such functional micronetworks tailored to and below the dimension of cells can enable future applications in technology and medicine like controlling cell interaction. %0 journal article %@ 1386-0291 %A Brunacci, N., Wischke, C., Naolou, T., Patzelt, A., Lademann, J., Neffe, A., Lendlein, A. %D 2021 %J Clinical Hemorheology and Microcirculation %N 2 %P 201-219 %R doi:10.3233/CH-200977 %T Formulation of drug-loaded oligodepsipeptide particles with submicron size %U https://doi.org/10.3233/CH-200977 2 %X The size of particulate carriers is key to their transport and distribution in biological systems, and needs to be tailored in the higher submicron range to enable follicular uptake for dermal treatment. Oligodepsipeptides are promising nanoparticulate carrier systems as they can be designed to exhibit enhanced interaction with drug molecules. Here, a fabrication scheme for drug-loaded submicron particles from oligo[3-(S)-sec-butylmorpholine-2,5-dione]diol (OBMD) is presented based on an emulsion solvent evaporation method with cosolvent, surfactant, and polymer concentration as variable process parameters. The particle size (300–950 nm) increased with lower surfactant concentration and higher oligomer concentration. The addition of acetone increased the particle size at low surfactant concentration. Particle size remained stable upon the encapsulation of models compounds dexamethasone (DXM) and Nile red (NR), having different physicochemical properties. DXM was released faster compared to NR due to its higher water solubility. Overall, the results indicated that both drug-loading and size control of OBMD submicron particles can be achieved. When applied on porcine ear skin samples, the NR-loaded particles have been shown to allow NR penetration into the hair follicle and the depth reached with the 300 nm particles was comparable to the one reached with the cream formulation. A potential benefit of the particles compared to a cream is their sustained release profile. %0 journal article %@ 1744-683X %A Friess, F., Lendlein, A., Wischke, C. %D 2021 %J Soft Matter %N 41 %P 9326-9331 %R doi:10.1039/d1sm00947h %T Switching microobjects from low to high aspect ratios using a shape-memory effect %U https://doi.org/10.1039/d1sm00947h 41 %X Spherical particles from shape-memory polymers (SMP) can be stretched to ellipsoids with high aspect ratio (AR) and temporarily stabilized. They can switch back to low AR upon thermal stimulation. Here, the creation of an alternative shape-switching capability of particles from low to high AR is introduced, where a SMP matrix from polyvinyl alcohol (PVA) is used to create crosslinked high AR particles and to program the embedded micrometer-sized particles from a second SMP (oligo(ε-caprolactone) micronetworks, MN) with a low switching temperature Tsw. This programming proceeds through shape-recovery of the PVA matrix, from which the MN are harvested by PVA matrix dissolution. The use of a dissolvable SMP matrix may be a general strategy to efficiently create systems with complex moving capabilities. %0 journal article %@ 2059-8521 %A Wischke, C., Kersting, M., Welle, A., Lysyakova, L., Braune, S., Kratz, K., Jung, F., Franzreb, M., Lendlein, A. %D 2020 %J MRS Advances %N 14 - 15 %P 773-783 %R doi:10.1557/adv.2020.218 %T Thin hydrogel coatings formation catalyzed by immobilized enzyme horseradish peroxidase %U https://doi.org/10.1557/adv.2020.218 14 - 15 %X Enzymes can be a renewable source of catalytic agents and thus be interesting for sustainable approaches to create and modify functional materials. Here, thin hydrogel layers were prepared as thin coatings on hard substrates by immobilized horseradish peroxidase. Hydrophilic 4-arm star shaped telechelics from oligo(ethylene glycol) bearing on average 55% end groups derived from aromatic amino acids served as monomers and enzymatic substrates. Shifts of the contact angle from 84° to 62° for the wetting process and of zeta potential towards the neutral range illustrated an alteration of physicochemical properties of the model surfaces by a hydrophilic shielding. Time-of-flight secondary ion mass spectrometry (ToF-SIMS), quartz crystal microbalance and atomic force microscopy (AFM) experiments enabled the qualitative and quantitative proof of hydrogel deposition at the interface with thicknesses in the medium nanometer size range. Conceptually, as the immobilized enzyme becomes entrapped in the hydrogel and the crosslinking mechanism bases on a radical reaction after enzymatic activation of the monomers with a limited diffusivity and lifetime, the formed network material can be assumed to be inhomogeneous on the molecular level. On the macroscale, however, relative homogeneity of the coating was observed via ToF-SIMS and AFM mapping. As an exemplary functional evaluation in view of bioanalytical applications, the thrombogenicity of the coating was studied in static tests with human blood from several donors. In the future, this “coating-from” approach may be explored for cell culture substrate coatings, for protein/biofilm repellence in technical applications, or in bioanalytical devices. %0 journal article %@ 2059-8521 %A Pang, J., Wischke, C., Lendlein, A. %D 2020 %J MRS Advances %N 12 - 13 %P 633-642 %R doi:10.1557/adv.2019.441 %T In vitro Degradation Analysis of 3D-architectured Gelatin-based Hydrogels %U https://doi.org/10.1557/adv.2019.441 12 - 13 %X Multifunctional biopolymer-based materials are promising candidates for next generation regenerative biomaterials. Understanding the degradation behavior of biomaterials is vital for ensuring biological safety, as well as for better control of degradation properties based on rational design of a material’s physical and chemical characteristics. In this study, we decipher the degradation of a hydrogel prepared from gelatin and lysine diisocyanate ethyl ester (LDI) using in vitro models, which simulate hydrolytic, oxidative and enzymatic degradation (collagenase). Gravimetrical, morphological, mechanical and chemical properties were evaluated. Notably, the hydrogels were relatively resistant to hydrolytic degradation, but degraded rapidly within 21 days (>95% mass loss) under oxidative and collagenase degradation. Oxidative and collagenase degradation rapidly decreased the storage and loss modulus of the hydrogels, and slightly increased their viscous component (tan δ). For each degradation condition, the results suggest different possible degradation pathways associated to the gelatin polypeptide backbone, urea linkages and ester groups. The primary degradation mechanisms for the investigated gelatin based hydrogels are oxidative and enzymatic in nature. The relative hydrolytic stability of the hydrogels should ensure minimal degradation during storage and handling prior to application in surgical theatres. %0 journal article %@ 0378-5173 %A Wischke, C. %D 2020 %J International Journal of Pharmaceutics %P 119401 %R doi:10.1016/j.ijpharm.2020.119401 %T Concepts for efficient preparation of particulate polymer carrier systems by droplet-based microfluidics %U https://doi.org/10.1016/j.ijpharm.2020.119401 %X Droplet-based microfluidics has grown out of its infancy as technical solutions became available for a broad community of researchers aiming at highly defined structures of polymer-based drug carrier systems. While the beauty of obtained particles and the precision of their (continuous) production may be very fascinating from a scientific perspective, microfluidics is further developing towards the use in production processes. This review summarizes recent concepts and developments in droplet-based microfluidics covering theoretical aspects of the operation principle as well as approaches to increased throughput and thus to enable efficient production. The application of microfluidic templating for preparing functional polymer particles including dispersions of preformed polymers, multicompartment particles and the use of template droplets as microreactors for carrier synthesis are also included. When operated at high-throughput, in a continuous process and with excellent control over particle properties, microfluidics may become a preparation technique for particulate carriers competitive to batch emulsification not only in research but also for commercial fabrication, e.g., of individualized, patient-specific formulations. %0 conference poster %@ %A Pang, J., Wischke, C., Lendlein, A. %D 2019 %J MRS Fall Meeting 2019 %T Preparation and Degradation Analysis of Multifunctional 3D-architectured Gelatin-based Hydrogels %U %X %0 conference poster %@ %A Wischke, C., Kersting, M., Welle, A., Lysyakova, L., Braune, S., Kratz, K., Franzreb, M., Lendlein, A. %D 2019 %J MRS Fall Meeting 2019 %T Thin hydrogel coatings by enzyme-catalyzed mechanism %U %X %0 journal article %@ 0168-3659 %A Brunacci, N., Neffe, A., Wischke, C., Naolou, T., Nöchel, U., Lendlein, A. %D 2019 %J Journal of Controlled Release %P 146-156 %R doi:10.1016/j.jconrel.2019.03.004 %T Oligodepsipeptide (nano)carriers: Computational design and analysis of enhanced drug loading %U https://doi.org/10.1016/j.jconrel.2019.03.004 %X High drug loads of nanoparticles are essential to efficiently provide a desired dosage in the required timeframe, however, these conditions may not be reached with so far established degradable matrices. Our conceptual approach for increasing the drug load is based on strengthening the affinity between drug and matrix in combination with stabilizing drug-matrix-hybrids through strong intermolecular matrix interactions. Here, a method for designing such complex drug-matrix hybrids is introduced employing computational methods (molecular dynamics and docking) as well as experimental studies (affinity, drug loading and distribution, drug release from films and nanoparticles). As model system, dexamethasone (DXM), relevant for the treatment of inflammatory diseases, in combination with poly[(rac-lactide)-co-glycolide] (PLGA) as standard degradable matrix or oligo[(3-(S)-sec-butyl)morpholine-2,5-dione]diol (OBMD) as matrix with hypothesized stronger interaction with DXM were investigated. Docking studies predicted higher affinity of DXM to OBMD than PLGA and displayed amide bond participation in hydrogen bonding with OBMD. Experimental investigations on films and nanoparticles, i.e. matrices of different shapes and sizes, confirmed this phenomenon as shown e.g. by a ~10 times higher solid state solubility of DXM in OBMD than in PLGA. DXM-loaded particles of ~ 150 nm prepared by nanoprecipitation in aqueous environment had a drug loading (DL) up to 16 times higher when employing OBMD as matrix compared to PLGA carriers due to enhanced drug retention in the OBMD phase. Importantly, drug relase periods were not altered as the release from films and particles was mainly ruled by the diffusion length as well as matrix degradation rather than the matrix type, which can be assigned to water diffusing into the matrix and breaking up of drug-matrix hydrogen bonds. Overall, the presented design and fabrication scheme showed predictive power and might universally enable the screening of drug/matrix interactions particularly to expand the oligodepsipeptide platform technology, e.g. by varying the depsipeptide side chains, for drug carrier and release systems. %0 book part %@ %A Razzaq, M.Y., Reinthaler, M., Schroeder, M., Wischke, C., Lendlein, A. %D 2019 %J Encyclopedia of Biomedical Engineering, Biomaterials: Biomaterial Applications and Advanced Medical Technologies %P 394-405 %R doi:10.1016/B978-0-12-801238-3.11041-4 %T Shape-memory polymer medical devices %U https://doi.org/10.1016/B978-0-12-801238-3.11041-4 %X Shape-memory polymers (SMPs) are stimuli-responsive materials, which allow spatially directed movements of devices upon external stimulation. This programmed movement is highly defined as it relies on the recovery of a device from a temporary, second shape to a permanent shape. The types of applicable stimuli to induce the shape switching as well as the specific conditions of material response can be tuned by altering the chemistry as well as the material organization on different hierarchical levels. Their ability to rapidly and automatically respond to changes in the environment makes SMPs suitable for a variety of biomedical applications, particularly for devices for minimally invasive surgery and for the delivery of therapeutics and cells. This article introduces the concepts of the shape-memory effect in polymers and their contribution to upcoming clinical demands for smart medical devices. %0 journal article %@ 2059-8521 %A Friess, F., Wischke, C., Lendlein, A. %D 2019 %J MRS Advances %N 59 - 60 %P 3199-3206 %R doi:10.1557/adv.2019.392 %T Microscopic analysis of shape-shiftable oligo (ε-caprolactone) — based particles %U https://doi.org/10.1557/adv.2019.392 59 - 60 %X Spherical particles are routinely monitored and described by hydrodynamic diameters determined, e.g., by light scattering techniques. Non-spherical particles such as prolate ellipsoids require alternative techniques to characterize particle size as well as particle shape. In this study, oligo(ε-caprolactone) (oCL) based micronetwork (MN) particles with a shape-shifting function based on their shape-memory capability were programmed from spherical to prolate ellipsoidal shape aided by incorporation and stretching in a water-soluble phantom matrix. By applying light microscopy with automated contour detection and aspect ratio analysis, differences in characteristic aspect ratio distributions of non-crosslinked microparticles (MPs) and crosslinked MNs were detected when the degrees of phantom elongation (30-290%) are increased. The thermally induced shape recovery of programmed MNs starts in the body rather than from the tips of ellipsoids, which may be explained based on local differences in micronetwork deformation. By this approach, fascinating intermediate particle shapes with round bodies and two opposite sharp tips can be obtained, which could be of interest, e.g., in valves or other technical devices, in which the tips allow to temporarily encage the switchable particle in the desired position. %0 journal article %@ 0378-5173 %A Friess, F., Roch, T., Seifert, B., Lendlein, A., Wischke, C. %D 2019 %J International Journal of Pharmaceutics %P 118461 %R doi:10.1016/j.ijpharm.2019.118461 %T Phagocytosis of spherical and ellipsoidal micronetwork colloids from crosslinked poly(ε-caprolactone) %U https://doi.org/10.1016/j.ijpharm.2019.118461 %X The effect of non-spherical particle shapes on cellular uptake has been reported as a general design parameter to control cellular recognition of particulate drug carriers. Beside shape, also size and cell-particle ratio should mutually effect phagocytosis. Here, the capability to control cellular uptake of poly(ɛ-caprolactone) (PCL) based polymer micronetwork colloids (MNC), a carrier system that can be transferred to various shapes, is explored in vitro at test conditions allowing multiple cell-particle contacts. PCL-based MNC were synthesized as spheres with a diameter of ∼6, ∼10, and 13 µm, loaded with a fluorescent dye by a specific technique of swelling, re-dispersion and drying, and transferred into different ellipsoidal shapes by a phantom stretching method. The boundaries of MNC deformability to prolate ellipsoid target shapes were systematically analyzed and found to be at an aspect ratio AR of ∼4 as obtained by a phantom elongation εph of ∼150%. Uptake studies with a murine macrophages cell line showed shape dependency of phagocytosis for selected conditions when varying particle sizes (∼6 and 10 μm),and shapes (εph: 0, 75 or 150%), cell-particle ratios (1:1, 1:2, 1:10, 1:50), and time points (1–24 h). For larger-sized MNC, there was no significant shape effect on phagocytosis as these particles may associate with more than one cell, thus increasing the possibility of phagocytosis by any of these cells. Accordingly, controlling shape effects on phagocytosis for carriers made from degradable polymers relevant for medical applications requires considering further parameters besides shape, such as kinetic aspects of the exposure and uptake by cells. %0 conference lecture %@ %A Wischke, C., Friess, F., Lendlein, A. %D 2018 %J 5th Symposium on Innovative Polymers for Controlled Delivery (SIPCD) 2018 %T Polymer network carriers that switch their shape %U %X particular, a switching of particles towards increased aspect ratios will be explored. %0 conference lecture %@ %A Wischke, C., Ceylan Tuncaboylu, D., Friess, F., Lendlein, A. %D 2018 %J Annual Meeting of the German Pharmaceutical Society - DPhG %T A multifunctional system for on-demand protein release %U %X %0 conference lecture (invited) %@ %A Wischke, C., Lendlein, A. %D 2018 %J Gesundheitswissenschaften - Perspektiven in der Lausitz, Workshop %T Interdisziplinaere Grundlagenforschung fuer eine altersgerechte Medizin %U %X %0 conference lecture %@ %A Wischke, C., Baehr, E., Racheva, M., Lendlein, A. %D 2018 %J ProcessNet-Jahrestagung und 33. DECHEMA-Jahrestagung der Biotechnologen 2018 %T Tyrosinase als Biokatalysator: Synthese von Hydrogelen und Oberflaechenfunktionalisierung %U %X %0 journal article %@ 0009-286X %A Wischke, C., Baehr, E., Racheva, M., Lendlein, A. %D 2018 %J Chemie - Ingenieur - Technik %N 9 %P 1292 %R doi:10.1002/cite.201855348 %T Tyrosinase als Biokatalysator: Synthese von Hydrogelen und Oberflaechenfunktionalisierung %U https://doi.org/10.1002/cite.201855348 9 %X No abstract %0 journal article %@ 2059-8521 %A Wischke, C., Baehr, E., Racheva, M., Heuchel, M., Weigel, T., Lendlein, A. %D 2018 %J MRS Advances %N 63 %P 3875-3881 %R doi:10.1557/adv.2018.630 %T Surface immobilization strategies for tyrosinase as biocatalyst applicable to polymer network synthesis %U https://doi.org/10.1557/adv.2018.630 63 %X Enzymes have recently attracted increasing attention in material research based on their capacity to catalyze the conversion of polymer-bound moieties for synthesizing polymer networks, particularly bulk hydrogels. In this study, the surface immobilization of a relevant enzyme, mushroom tyrosinase, should be explored using glass as model surface. In a first step, the glass support was functionalized with silanes to introduce either amine or carboxyl groups, as confirmed e.g. by X-ray photoelectron spectroscopy. By applying glutaraldehyde and EDC/NHS chemistry, respectively, surfaces have been activated for subsequent successful coupling of tyrosinase. Via protein hydrolysis and amino acid characterization by HPLC, the quantity of bound tyrosinase was shown to correspond to a full surface coverage. Based on the visualized enzymatic conversion of a test substrate at the glass support, the functionalized surfaces may be explored for surface-associated material synthesis in the future. %0 conference lecture %@ %A Wischke, C., Baehr, E., Racheva, M., Heuchel, M., Weigel, T., Lendlein, A. %D 2018 %J 27th International Materials Research Congress %T Surface immobilization strategies for tyrosinase as biocatalyst applicable to polymer network synthesis %U %X %0 conference poster %@ %A Friess, F., Roch, B., Seifert, B., Lendlein, A., Wischke, C. %D 2018 %J Advanced Functional Polymers for Medicine, AFPM 2018 %T Limited Shape-dependency of Phagocytosis for Polymer Micronetworks %U %X %0 journal article %@ 0168-3659 %A Ceylan Tuncaboylu, D., Friess, F., Wischke, C., Lendlein, A. %D 2018 %J Journal of Controlled Release %P 240-247 %R doi:10.1016/j.jconrel.2018.06.022 %T A multifunctional multimaterial system for on-demand protein release %U https://doi.org/10.1016/j.jconrel.2018.06.022 %X In order to provide best control of the regeneration process for each individual patient, the release of protein drugs administered during surgery may need to be timely adapted and/or delayed according to the progress of healing/regeneration. This study aims to establish a multifunctional implant system for a local on-demand release, which is applicable for various types of proteins. It was hypothesized that a tubular multimaterial container kit, which hosts the protein of interest as a solution or gel formulation, would enable on-demand release if equipped with the capacity of diameter reduction upon external stimulation. Using devices from poly(ɛ-caprolactone) networks, it could be demonstrated that a shape-memory effect activated by heat or NIR light enabled on-demand tube shrinkage. The decrease of diameter of these shape-memory tubes (SMT) allowed expelling the payload as demonstrated for several proteins including SDF-1α, a therapeutically relevant chemotactic protein, to achieve e.g. continuous release with a triggered add-on dosing (open tube) or an on-demand onset of bolus or sustained release (sealed tube). Considering the clinical relevance of protein factors in (stem) cell attraction to lesions and the progress in monitoring biomarkers in body fluids, such on-demand release systems may be further explored e.g. in heart, nerve, or bone regeneration in the future. %0 journal article %@ 1042-7147 %A Dal Bianco, A., Wischke, C., Zhou, S., Lendlein, A. %D 2017 %J Polymers for Advanced Technologies %N 10 %P 1263-1268 %R doi:10.1002/pat.3917 %T Controlling surface properties and permeability of polyglycerol network films %U https://doi.org/10.1002/pat.3917 10 %X While branched polyglycerol (PG)-based molecules are well established as hydrophilic particles, the capacity of utilizing PG in bulk materials and opportunities arising by their further surface functionalization have only recently been considered. Here we investigated how the mold used in PG network synthesis may affect surface composition and how the permeability of substances through PG can be controlled by altering network structure, i.e. introducing 20 mol% oligoethylene glycol (OEG) bifunctional spacer molecules. Overall, PG-based bulk network materials were shown to be tailorable, hydrophilic, low swelling and relatively stiff polyether-based materials, with low impact of salt onto material properties. Based on these features, but also on the principal capacity of free hydroxyl groups to be used for functionalization reactions, these materials may be an interesting platform for medical and technical applications, e.g. as diffusion-rate controlling membrane in aqueous environment. %0 journal article %@ 1042-7147 %A Balk, M., Behl, M., Yang, J., Li, Q., Wischke, C., Feng, Y., Lendlein, A. %D 2017 %J Polymers for Advanced Technologies %N 10 %P 1278-1284 %R doi:10.1002/pat.3911 %T Design of polycationic micelles by self‐assembly of polyethyleneimine functionalized oligo[(ε‐caprolactone)‐co‐glycolide] ABA block copolymers %U https://doi.org/10.1002/pat.3911 10 %X Cationic polymeric micelles are of interest as delivery materials for nucleotides allowing condensation and transport of anionic macromolecules and enabling the reduction of cytotoxicity of polyethyleneimine, the current standard of vectors for non-viral nucleic acid delivery. In addition, micelles based on a degradable core would be capable to degrade hydrolytically and release their payload, which should preferably occur after uptake in early endosomes providing a pH of 5.5. We explored whether degradable and amphiphilic ABA block copolymers from hyperbranched polyethyleneimine A blocks and B blocks based on hydrophobic oligoesters (CG) can be created, which can degrade in a pH range relevant for the early endosomes. CG was synthesized by ring-opening polymerization of ε-caprolactone and diglycolide. Polycationic micelles with particle sizes between 19 ± 1 and 43 ± 2 nm were obtained by self-assembly of the ABA block copolymers with different chain lengths of B blocks and/or co-assembly with a diblock copolymer from poly(ethylene glycol) (PEG) functionalized CG oligoester in phosphate-buffered saline solution. Mixed micelles containing PEG-CG showed a decreased zeta potential, suggesting a shielding by dangling PEG chains at the micelle surfaces. Sizes of cationic micelles were stable at pH = 7.4 over the studied time period of 2 weeks at 37 °C. The hydrolytic degradation was controlled by the composition of the CG core and was accelerated when the pH was decreased to 5.5 as detected by increasing micelle sizes. In this way, the polycationic micelles may act as an on-demand delivery system of condensed macromolecules. %0 journal article %@ 1381-5148 %A Ceylan Tuncaboylu, D., Wischke, C., Stoermann, F., Lendlein, A. %D 2017 %J Reactive and Functional Polymers %P 68-73 %R doi:10.1016/j.reactfunctpolym.2016.12.015 %T Microgels from microfluidic templating and photoinduced crosslinking of cinnamylidene acetic acid modified precursors %U https://doi.org/10.1016/j.reactfunctpolym.2016.12.015 %X So far, a number of approaches to synthesize microgel networks have been followed, while only in few cases a detailed control of the network architecture has been possible. Here, the photoinduced [2 + 2] cycloaddition reaction of cinnamylidene acetic acid (CAA) moieties coupled to four-arm star shaped oligo(ethylene glycol) (OEG) precursors was explored for the creation of microgels with defined polymer network structures. Based on a rational solvent selection and precursor dispersion in glass-capillary microfluidics, microgels could be successfully prepared by the proposed synthesis approach. Model reactions confirmed a quantitative network formation. Therefore, compared to common radical polymerization for microgel crosslinking, CAA-dimerization may be an alternative approach particularly when well defined network structures are desired. %0 journal article %@ 1525-7797 %A Wang, W., Naolou, T., Ma, N., Deng, Z., Xu, X., Mansfeld, U., Wischke, C., Gossen, M., Neffe, A.T., Lendlein, A. %D 2017 %J Biomacromolecules %N 11 %P 3819-3833 %R doi:10.1021/acs.biomac.7b01034 %T Polydepsipeptide Block-Stabilized Polyplexes for Efficient Transfection of Primary Human Cells %U https://doi.org/10.1021/acs.biomac.7b01034 11 %X The rational design of a polyplex gene carrier aims to balance maximal effectiveness of nucleic acid transfection into cells with minimal adverse effects. Depsipeptide blocks with an Mn ∼ 5 kDa exhibiting strong physical interactions were conjugated with PEI moieties (2.5 or 10 kDa) to di- and triblock copolymers. Upon nanoparticle formation and complexation with DNA, the resulting polyplexes (sizes typically 60–150 nm) showed remarkable stability compared to PEI-only or lipoplex and facilitated efficient gene delivery. Intracellular trafficking was visualized by observing fluorescence-labeled pDNA and highlighted the effective cytoplasmic uptake of polyplexes and release of DNA to the perinuclear space. Specifically, a triblock copolymer with a middle depsipeptide block and two 10 kDa PEI swallowtail structures mediated the highest levels of transgenic VEGF secretion in mesenchymal stem cells with low cytotoxicity. These nanocarriers form the basis for a delivery platform technology, especially for gene transfer to primary human cells. %0 book part %@ %A Lendlein, A., Razzaq, M.Y., Wischke, C., Kratz, K., Heuchel, M., Zotzmann, J., Hiebl, B., Neffe, A.T., Behl, M. %D 2017 %J Comprehensive Biomaterials II - Reference Module in Materials Science and Materials Engineering, Metallic, Ceramic, and Polymeric Biomaterials %P 620-647 %R doi:10.1016/B978-0-12-803581-8.10213-9 %T Shape-Memory Polymers %U https://doi.org/10.1016/B978-0-12-803581-8.10213-9 %X Medical devices such as implants, surgical instruments, extracorporal devices, and wound covers, as well as controlled drug delivery systems (CDDS) require a specific combination of material properties and functions including, for example, mechanical stability, biocompatibility, and biofunctionality. Polymeric biomaterials are of high relevance for such applications, as properties and functions can be tuned in a wide range by only small defined variations of their chemical or morphological structure. The rapid progress in surgical techniques, especially in minimally invasive surgery, requires smart materials, which are capable of an active on-demand movement and which do not need to be removed in a second surgery. These challenges can be addressed by shape-memory polymers (SMPs) described in this chapter. SMPs are of high technological significance for biomedical applications as they enable on-demand predefined changes in the shape of a device upon exposure to a suitable stimulus such as heat or alternating magnetic field (AMF). Multifunctional materials are obtained when the shape-memory effect is combined with an additional function such as hydrolytic degradability, biofunctionality, and controlled drug release. Selected biomaterials with shape-memory capability are presented, including data on their biocompatibility. The potential of SMPs as a platform technology for biomedical applications is sketched by an overview on SMP-based medical devices being developed and the potential use of SMPs as matrix for CDDS. %0 conference lecture %@ %A Brunacci, N., Wischke, C., Neffe, A., Lendlein, A. %D 2017 %J BIFTM PhD Symposium - BioInterfaces in Technology and Medicine %T Evaluation of surfactants for the formation of sub-micron depsipeptide particles %U %X %0 conference poster %@ %A Altabal, O., Wischke, C., Lendlein, A. %D 2017 %J XXVI International Materials Research Congress (IMRC) 2017; Symp. F4: Shape-memory and self-repairing materials %T Controlled deformation of polymer substrates with negative poisson ratio %U %X %0 journal article %@ 0001-4842 %A Löwenberg, C., Balk, M., Wischke, C., Behl, M., Lendlein, A. %D 2017 %J Accounts of Chemical Research %N 4 %P 723-732 %R doi:10.1021/acs.accounts.6b00584 %T Shape-Memory Hydrogels: Evolution of Structural Principles To Enable Shape Switching of Hydrophilic Polymer Networks %U https://doi.org/10.1021/acs.accounts.6b00584 4 %X In this Account, the principles of hydrogel network design, incorporation of molecular switches, and hydrogel microstructures are summarized that enable a spatially directed actuation of hydrogels by a shape-memory effect (SME) without major volume alteration. The SME involves an elastic deformation (programming) of samples, which are temporarily fixed by reversible covalent or physical cross-links resulting in a temporary shape. The material can reverse to the original shape when these molecular switches are affected by application of a suitable stimulus. Hydrophobic shape-memory polymers (SMPs), which are established with complex functions including multiple or reversible shape-switching, may provide inspiration for the molecular architecture of shape-memory hydrogels (SMHs), but cannot be identically copied in the world of hydrophilic soft materials. For instance, fixation of the temporary shape requires cross-links to be formed also in an aqueous environment, which may not be realized, for example, by crystalline domains from the hydrophilic main chains as these may dissolve in presence of water. Accordingly, dual-shape hydrogels have evolved, where, for example, hydrophobic crystallizable side chains have been linked into hydrophilic polymer networks to act as temperature-sensitive temporary cross-links. By incorporating a second type of such side chains, triple-shape hydrogels can be realized. Considering the typically given light permeability of hydrogels and the fully hydrated state with easy permeation by small molecules, other types of stimuli like light, pH, or ions can be employed that may not be easily used in hydrophobic SMPs. In some cases, those molecular switches can respond to more than one stimulus, thus increasing the number of opportunities to induce actuation of these synthetic hydrogels. Beyond this, biopolymer-based hydrogels can be equipped with a shape switching function when facilitating, for example, triple helix formation in proteins or ionic interactions in polysaccharides. Eventually, microstructured SMHs such as hybrid or porous structures can combine the shape-switching function with an improved performance by helping to overcome frequent shortcomings of hydrogels such as low mechanical strength or volume change upon temporary cross-link cleavage. Specifically, shape switching without major volume alteration is possible in porous SMHs by decoupling small volume changes of pore walls on the microscale and the macroscopic sample size. Furthermore, oligomeric rather than short aliphatic side chains as molecular switches allow stabilization of the sample volumes. Based on those structural principles and switching functionalities, SMHs have already entered into applications as soft actuators and are considered, for example, for cell manipulation in biomedicine. In the context of those applications, switching kinetics, switching forces, and reversibility of switching are aspects to be further explored. %0 journal article %@ 0939-6411 %A Zhang, N., Said, A., Wischke, C., Kral, V., Brodwolf, R., Volz, P., Boreham, A., Gerecke, C., Li, W., Neffe, A.T., Kleuser, B., Alexiev, U., Lendlein, A., Schaefer-Korting, M. %D 2017 %J European Journal of Pharmaceutics and Biopharmaceutics %P 66-75 %R doi:10.1016/j.ejpb.2016.10.019 %T Poly[acrylonitrile-co-(N-vinyl pyrrolidone)] nanoparticles – Composition-dependent skin penetration enhancement of a dye probe and biocompatibility %U https://doi.org/10.1016/j.ejpb.2016.10.019 %X Nanoparticles can improve topical drug delivery: size, surface properties and flexibility of polymer nanoparticles are defining its interaction with the skin. Only few studies have explored skin penetration for one series of structurally related polymer particles with systematic alteration of material composition. Here, a series of rigid poly[acrylonitrile-co-(N-vinyl pyrrolidone)] model nanoparticles stably loaded with Nile Red or Rhodamin B, respectively, was comprehensively studied for biocompatibility and functionality. Surface properties were altered by varying the molar content of hydrophilic NVP from 0 to 24.1% and particle size ranged from 35 to 244 nm. Whereas irritancy and genotoxicity were not revealed, lipophilic and hydrophilic nanoparticles taken up by keratinocytes affected cell viability. Skin absorption of the particles into viable skin ex vivo was studied using Nile Red as fluorescent probe. Whilst an intact stratum corneum efficiently prevented penetration, almost complete removal of the horny layer allowed nanoparticles of smaller size and hydrophilic particles to penetrate into viable epidermis and dermis. %0 journal article %@ 0939-6411 %A Brunacci, N., Wischke, C., Naolou, T., Neffe, A.T., Lendlein, A. %D 2017 %J European Journal of Pharmaceutics and Biopharmaceutics %P 61-65 %R doi:10.1016/j.ejpb.2016.11.011 %T Influence of surfactants on depsipeptide submicron particle formation %U https://doi.org/10.1016/j.ejpb.2016.11.011 %X Surfactants are required for the formation and stabilization of hydrophobic polymeric particles in aqueous environment. In order to form submicron particles of varying sizes from oligo[3-(S)-sec-butylmorpholine-2,5-dione]diols ((OBMD)-diol), different surfactants were investigated. As new surfactants, four-armed star-shaped oligo(ethylene glycol)s of molecular weights of 5–20 kDa functionalized with desamino-tyrosine (sOEG-DAT) resulted in smaller particles with lower PDI than with desaminotyrosyl tyrosine (sOEG-DATT) in an emulsion/solvent evaporation method. In a second set of experiments, sOEG-DAT of Mn = 10 kDa was compared with the commonly employed emulsifiers polyvinylalcohol (PVA), polyoxyethylene (20) sorbitan monolaurate (Tween 20), and D-α-tocopherol polyethylene glycol succinate (VIT E-TPGS) for OBMD particle preparation. sOEG-DAT allowed to systematically change sizes in a range of 300 up to 900 nm with narrow polydispersity, while in the other cases, a lower size range (250–400 nm, PVA; ∼300 nm, Tween 20) or no effective particle formation was observed. The ability of tailoring particle size in a broad range makes sOEG-DAT of particular interest for the formation of oligodepsipeptide particles, which can further be investigated as drug carriers for controlled delivery. %0 conference lecture %@ %A Wischke, C., Racheva, M., Störmann, F., Bähr, E., Lendlein, A. %D 2017 %J MRS Spring Meeting 2017 %T Functional hydrogels and particles from crosslinked polymeric telechelics %U %X %0 journal article %@ 0168-3659 %A Vogt, A., Wischke, C., Neffe, A.T., Ma, N., Alexiev, U., Lendlein, A. %D 2016 %J Journal of Controlled Release %P 3-15 %R doi:10.1016/j.jconrel.2016.07.027 %T Nanocarriers for drug delivery into and through the skin - Do existing technologies match clinical challenges? %U https://doi.org/10.1016/j.jconrel.2016.07.027 %X The topical application of drug-loaded particles has been explored extensively aiming at a dermal, follicular or transdermal drug delivery. This review summarizes the present state of the field of polymeric nanocarriers for skin application, also covering methodologies to clinically characterize their interaction and penetration in skin in vivo. Furthermore, with a focus on a clinical perspective, a number of questions are addressed: How well are existing nanoparticle systems penetrating the skin? Which functions of new carrier concepts may meet the clinical requirements? To which extend will instrumental imaging techniques provide information on the biological functions of nanocarriers? Which issues have to be addressed for translating experimental concepts into a future clinical application? %0 journal article %@ 0169-409X %A Balk, M., Behl, M., Wischke, C., Zotzmann, J., Lendlein, A. %D 2016 %J Advanced Drug Delivery Reviews %P 136-152 %R doi:10.1016/j.addr.2016.05.012 %T Recent advances in degradable lactide-based shape-memory polymers %U https://doi.org/10.1016/j.addr.2016.05.012 %X Biodegradable polymers are versatile polymeric materials that have a high potential in biomedical applications avoiding subsequent surgeries to remove, for example, an implanted device. In the past decade, significant advances have been achieved with poly(lactide acid) (PLA)-based materials, as they can be equipped with an additional functionality, that is, a shape-memory effect (SME). Shape-memory polymers (SMPs) can switch their shape in a predefined manner upon application of a specific external stimulus. Accordingly, SMPs have a high potential for applications ranging from electronic engineering, textiles, aerospace, and energy to biomedical and drug delivery fields based on the perspectives of new capabilities arising with such materials in biomedicine. This study summarizes the progress in SMPs with a particular focus on PLA, illustrates the design of suitable homo- and copolymer structures as well as the link between the (co)polymer structure and switching functionality, and describes recent advantages in the implementation of novel switching phenomena into SMP technology. %0 editorial %@ 1743-5889 %A Wischke, C., Lendlein, A. %D 2016 %J Nanomedicine %N 12 %P 1507-1509 %R doi:10.2217/nnm.16.45 %T Editorial: Functional nanocarriers by miniaturization of polymeric materials %U https://doi.org/10.2217/nnm.16.45 12 %X No abstract %0 editorial %@ 0168-3659 %A Wischke, C., Ruehl, E., Lendlein, A. %D 2016 %J Journal of Controlled Release %P 1-2 %R doi:10.1016/j.jconrel.2016.10.025 %T Editorial: Dermal Drug Delivery by Nanocarriers %U https://doi.org/10.1016/j.jconrel.2016.10.025 %X No abstract %0 journal article %@ 0168-3659 %A Wang, W., Balk, M., Deng, Z., Wischke, C., Gossen, M., Behl, M., Ma, N., Lendlein, A. %D 2016 %J Journal of Controlled Release %P 71-79 %R doi:10.1016/j.jconrel.2016.08.004 %T Engineering biodegradable micelles of polyethylenimine-based amphiphilic block copolymers for efficient DNA and siRNA delivery %U https://doi.org/10.1016/j.jconrel.2016.08.004 %X Polycationic micelles have shown advantageous properties as nucleic acid delivery vectors both in vitro and in vivo. In contrast to polycationic micelles reported so far, we designed particles integrating a sufficient nucleic acid condensation capability by polycationic polyethylenimine (PEI) segments as well as only a mild cytotoxic behavior. The micelles composed of a hydrophobic oligoester core with glycolide units resulting in fast degradation after cellular internalization in combination with PEG moieties acting as shielding agents. By grafting branched 25 kDa polyethylenimine (PEI25) and poly(ethylene glycol) (PEG) on poly[(ε-caprolactone)-co-glycolide] (CG), amphiphilic PEI-CG-PEI and PEG-CG block copolymers were used to form a series of micelles via self-assembly of PEI-CG-PEI or co-assembly of both copolymers for DNA and siRNA delivery. This modular system enabled a systematic investigation of different parameters and their synergetic effects as different functions were introduced. The polyplex formation and serum stability, cytotoxicity, and transfection activity could be tailored by changing the CG chain length in PEI-based copolymer, incorporating PEG-CG, and varying the N/P ratio. All micelle-based polyplex compositions showed high DNA transfection activity according to reporter gene-expression and an exceptionally high knockdown in siRNA delivery experiments. Remarkably, the GFP expression of > 99% cells was successfully knocked down by micelle-mediated siRNA interference, resulting in a decrease of two orders of magnitude in fluorescence intensity. Incorporation of PEG-CG in the micelles reduced the PEI-related cytotoxicity, and markedly enhanced the serum stability of both DNA and siRNA polyplexes. Compared with homo-PEI25, these micelles showed several advantages including the lower toxicity, higher siRNA transfection efficiency and higher polyplex stability in the presence of serum. This study therefore provides an effective approach to tune the structure, property and function of polycationic micelles for efficient DNA and siRNA delivery, which could contribute to the design and development of novel non-viral transfection vectors with superb functionality. %0 journal article %@ 2059-8521 %A Friess, F., Lendlein, A., Wischke, C. %D 2016 %J MRS Advances %N 27 %P 2019-2024 %R doi:10.1557/adv.2016.493 %T Two phase microfluidics with inviscid drops: Effects of total flow rate and delayed surfactant addition %U https://doi.org/10.1557/adv.2016.493 27 %X The microfluidic production of droplets is a well controllable process, which allows templating small spherical containers that can subsequently be transferred into uniformly sized polymer microgel particles by a crosslinking reaction. Recently, the per-channel production rate of N-isopropylacrylamide (NIPAAm) droplets (w-phase) dispersed in a low-viscosity fluorocarbon oil (o-phase) could be increased by a delayed surfactant addition, while maintaining the advantageous dripping regime. Here it should be evaluated, if delayed surfactant addition can be applied to enhance droplet production also for high viscosity continuous phases, which is associated with a change to an inviscid drop scenario compared to the previously used setting of viscous drops. It could be illustrated that the concept of delayed surfactant addition holds true also for viscous continuous phases and allows ∼8 fold increased flow rates in the dripping regime. Surprisingly, the droplet size increased at higher total flow rate with constant flow rate ratios of w- and o-phases, which is discussed in the light of viscous dissipation, microchannel bulging and viscosity of the continuous phase. More rigid microchannels such as from glass may allow further exploring this phenomenon in the future. %0 conference poster %@ %A Brunacci, N., Naolou, T., Neffe, A.T., Wischke, C., Lendlein, A. %D 2016 %J International Conference on Dermal Drug Delivers by Nanocarrierrs, SFB Konferenz %T Evaluation of surfactants for the formation of sub-micron depsipeptide particles %U %X %0 conference poster %@ %A Zhang, N., Said, A., Wischke, C., Kral, V., Brodwolf, R., Boreham, A., Gerecke, C., Li, W., Neffe, A.T., Kleuser, B., Alexiev, U., Lendlein, A., Schaefer-Korting, M. %D 2016 %J International Conference on Dermal Drug Delivers by Nanocarrierrs, SFB Konferenz %T Composition-dependent skin penetration and toxicity of a series of poly[acrylonitrile-co-(N-vinyl pyrrolidone)] nanoparticles %U %X %0 journal article %@ 1543-8384 %A Zhang, Y., Wischke, C., Mittal, S., Mitra, A., Schwendeman, S.P. %D 2016 %J Molecular Pharmaceutics %N 8 %P 2622-2630 %R doi:10.1021/acs.molpharmaceut.5b00961 %T Design of Controlled Release PLGA Microspheres for Hydrophobic Fenretinide %U https://doi.org/10.1021/acs.molpharmaceut.5b00961 8 %X Fenretinide, a chemotherapeutic agent for cancer, is water-insoluble and has a very low oral bioavailability. Hence, the objective was to deliver it as an injectable depot and improve the drug solubility and release behavior from poly(lactide-co-glycolide) (PLGA) microspheres by incorporating nonionic surfactants with fenretinide. Enhancement of drug solubilization was observed with Brij 35 or 98, Tween 20, and Pluronic F127, but not Pluronic F68. Co-incorporation of Brij 98 with fenretinide significantly changed the microsphere morphology and improved the fenretinide release profile. The most optimal microsphere formulation, with 20% Brij 98 as excipient, showed an initial in vitro burst around 20% and a sustained release over 28 days in a solubilizing release medium at 37 °C. The effect of addition of MgCO3, drug loading, and polymer blending on the release of fenretinide from PLGA microspheres was also investigated and observed to enhance the drug release. Two sustained release formulations, one incorporating 20% Brij 98 and the other incorporating 3% MgCO3 in the oil phase, were selected for dosing in Sprague–Dawley rats and compared to a single injection of an equivalent dose of fenretinide drug suspension. These two formulations were chosen due to their high encapsulation efficiency, high cumulative release, and desirable in vitro release profile. The drug suspension resulted in a higher initial release in rats compared to the polymeric formulations, however, sustained release was also observed beyond 2 weeks, which may be attributed to the physiological disposition of the drug in vivo. The two PLGA based test formulations provided the desired low initial burst of fenretinide followed by 4 weeks of in vivo sustained release. %0 journal article %@ 2280-8000 %A Trajkovski, B., Petersen, A., Perka, C., Scharnagl, N., Mathew, S., Wischke, C., Lendlein, A., Duda, G.N. %D 2016 %J Journal of Applied Biomaterials & Functional Materials %N 2 %P e143-e153 %R doi:10.5301/jabfm.5000270 %T A double-layer patch design for local and controlled drug delivery as an intraoperative custom-made implant-coating technology %U https://doi.org/10.5301/jabfm.5000270 2 %X Double-layered patches with 1 layer for drug delivery and 1 as gluing interface could represent a solution for safe and controlled local drug delivery from implant surfaces or other, even biological, materials. The technology platform presented here opens the opportunity for personalized medicine by allowing local administration of drugs with customized release based on an intraoperative application. %0 conference poster %@ %A Wischke, C., Tuncaboylu, D.C., Lendlein, A. %D 2016 %J International Conference on Dermal Drug Delivers by Nanocarrierrs, SFB Konferenz %T Microgels from photocrosslinking of cinnamylidene acetic acid modified polyethylene glycol %U %X %0 conference lecture %@ %A Lendlein, A., Neffe, A.T., Ma, N., Behl, M., Wischke, C. %D 2016 %J International Conference on Dermal Drug Delivers by Nanocarrierrs, SFB Konferenz %T Functional Polymers and Carriers Systems %U %X %0 conference lecture %@ %A Wischke, C. %D 2016 %J Multifunctional Biomaterials for Medicine, HVI Symposium 2016 %T Accelerated microfluidic production of polymer particles %U %X %0 conference poster %@ %A Balk, M., Behl, M., Yang, J., Li, Q., Wischke, C., Feng, Y., Lendlein, A. %D 2016 %J Advanced Functional Polymers for Medicine, AFPM 2016 %T Design of Polycationic Micelles by Self-Assembly of Polyethyleneimine Functionalized Oligo[(ε-caprolactone)-co-glycolide] ABA Block Copolymers %U %X %0 conference poster %@ %A Racheva, M., Wischke, C., Lendlein, A. %D 2016 %J International Conference on Molecular Interaction Engineering, MIE 2016 %T Tyrosinase as biocatalyst for hydrogel synthesis: side reactions affecting bioactive molecules %U %X %0 conference lecture %@ %A Neffe, A., Federico, S., Piluso, S., Löwenberg, C., Pierce, B., Nöchel, U., Wischke, C., Lendlein, A. %D 2016 %J Polydays 2016 %T Design Strategy for the Elucidation of Protein-Protein-Binding Epitopes; and Application of the Derived Peptides in Biomaterials %U %X %0 conference poster %@ %A Brunacci, N., Naolou, T., Wischke, C., Neffe, A., Lendlein, A. %D 2016 %J Polydays 2016 %T Depsipeptide submicron particles of different sizes as drug delivery systems %U %X %0 conference lecture %@ %A Wischke, C., Kratz, K., Lendlein, A. %D 2016 %J International Conference on Molecular Interaction Engineering, MIE 2016 %T Functional Materials and Interfaces %U %X %0 conference lecture %@ %A Lendlein, A., Neffe, A.T., Ma, N., Behl, M., Wischke, C. %D 2016 %J Multifunctional Biomaterials for Medicine, HVI Symposium 2016 %T Functional Polymers and Carriers Systems %U %X %0 conference poster %@ %A Balk, M., Behl, M., Yang, J., Li, Q., Wischke, C., Feng, Y., Lendlein, A. %D 2016 %J Integrating function into polymers, Polydays 2016 %T Design of Polycationic Micelles by Self-Assembly of Polyethyleneimine Functionalized Oligo[(ε-aprolactone)-co-glycolide] ABA Block Copolymers %U %X %0 conference lecture %@ %A Wischke, C., Seifert, B., Lendlein, A. %D 2016 %J Materialien fuer medizinische Anwendungen, RMIB-AG %T Sterilisation von Polymeren %U %X %0 conference lecture (invited) %@ %A Wischke, C., Lendlein, A. %D 2016 %J 30. Treffpunkt Medizintechnik 2016 %T Polymerbasierte Materialien fuer Technologie und Medizin %U %X %0 conference lecture (invited) %@ %A Wischke, C., Lendlein, A. %D 2016 %J 9. Innovationsforum Senftenberg %T Benefits and Perspective of interdisziplinary research %U %X %0 conference poster %@ %A Brunacci, N., Naolou, T., Wischke, C., Neumann, F., Ma, N., Neffe, A.T., Lendlein, A. %D 2016 %J Advanced Functional Polymers for Medicine, AFPM 2016 %T Comparison of particulate carriers for dexamethasone with oligodepsipeptide or OLGA as matrix material %U %X %0 conference poster %@ %A Dal Bianco, A., Zhou, S., Wischke, C., Lendlein, A. %D 2016 %J Advanced Functional Polymers for Medicine, AFPM 2016 %T Surface properties and permeability of polyglycerol films %U %X %0 journal article %@ 0378-5173 %A Staufenbiel, S., Merino, M., Li, W., Huang, M.-D., Baudis, S., Lendlein, A., Mueller, R.H., Wischke, C. %D 2015 %J International Journal of Pharmaceutics %N 1-2 %P 87-96 %R doi:10.1016/j.ijpharm.2015.02.072 %T Surface characterization and protein interaction of a series of model poly[acrylonitrile-co-(N-vinyl pyrrolidone)] nanocarriers for drug targeting %U https://doi.org/10.1016/j.ijpharm.2015.02.072 1-2 %X The surface properties of intravenously injected nanoparticles determine the acquired blood protein adsorption pattern and subsequently the organ distribution and cellular recognition. A series of poly[acrylonitrile-co-(N-vinyl pyrrolidone)] (PANcoNVP) model nanoparticles (133–181 nm) was synthesized, in which the surface properties were altered by changing the molar content of NVP (0–33.8 mol%) as the more hydrophilic repeating unit. The extent of achieved surface property variation was comprehensively characterized. The residual sodium dodecyl sulfate (SDS) content from the synthesis was in the range 0.3–1.6 μg ml−1, potentially contributing to the surface properties. Surface hydrophobicity was determined by Rose Bengal dye adsorption, hydrophobic interaction chromatography (HIC) and aqueous two-phase partitioning (TPP). Particle charge was quantified by zeta potential (ZP) measurements including ZP–pH profiles. The interaction with proteins was analyzed by ZP measurements in serum and by adsorption studies with single proteins. Compared to hydrophobic polystyrene model nanoparticles, all PANcoNVP particles were very hydrophilic. Differences in surface hydrophobicity could be detected, which did not linearly correlate with the systematically altered bulk composition of the PANcoNVP nanoparticles. This proves the high importance of a thorough surface characterization applying a full spectrum of methods, complementing predictions solely based on bulk polymer composition. %0 journal article %@ 1946-4274 %A Racheva, M., Romero, O., Julich-Gruner, K.K., Ulrich, A.S., Wischke, C., Lendlein, A. %D 2015 %J MRS Online Proceedings Library %P 36-41 %R doi:10.1557/opl.2015.260 %T Purity of mushroom tyrosinase as a biocatalyst for biomaterial synthesis affects the stability of therapeutic peptides %U https://doi.org/10.1557/opl.2015.260 %X The formation of injectable implants in the presence of cells or solutes has previously been conceptualized to be based on the selectivity of bioorthogonal chemical reactions. As an alternative approach, hydrogel network synthesis by enzymatic reactions with a typically high inherent substrate specificity and low toxicity have been repeatedly proposed, e.g. using commercial mushroom tyrosinase (MTyr), which specifically catalyzes phenol oxidation. In this study, it should be explored whether MTyr is compatible with therapeutic peptides that may be delivered from such hydrogels in the future. Based on the specificity of MTyr to phenol residues, no modification of peptides lacking the amino acid tyrosine would be expected. One example of such peptides is gramicidin S (GS), a potent antimicrobial peptide. However, when GS was incubated with commercial MTyr, peptide degradation occurred as observed by HPLC analysis. Several fragments of the peptide were detected by MALDI-TOF. Contamination of MTyr with peptidases was proven as the source of undesired peptide cleavage, which needs to be considered when preparing enzymatically crosslinked hydrogels for biomedical applications. %0 journal article %@ 1946-4274 %A Wischke, C., Weigel, J., Lendlein, A. %D 2015 %J MRS Online Proceedings Library %P 30-35 %R doi:10.1557/opl.2015.60 %T Poly(n-butylcyanoacrylate) Nanoparticles as Carriers for Adenosine triphosphate %U https://doi.org/10.1557/opl.2015.60 %X Adenosine triphosphate (ATP) has numerous biological functions both intra- and extracellularly, including effects on the directed migration of cells with a regenerative potential in brain tissue. Therefore, carrier systems would be of interest that would be capable to be loaded with ATP and release it in a controlled manner. In the present study, poly(n-butylcyanoacrylate) (PBCA) nanoparticles as a potential carrier system were prepared by anionic polymerization using different polymerization media, which resulted in different zeta potential values and in some cases aggregation of nanoparticles. By decorating the particle surface with positively charged diethylaminoethyl dextran, multivalent ionic interaction allowed to load ATP to the nanoparticles by adsorption. In release experiments, an ATP release over 6 hours was observed. ATP-loaded nanoparticles may thus be suitable to explore biological effects of short-term ATP delivery for biomedical applications. %0 journal article %@ 1946-4274 %A Stoermann, F., Wischke, C., Lendlein, A. %D 2015 %J MRS Online Proceedings Library %P 95-100 %R doi:10.1557/opl.2015.494 %T Photo-Reversibility of Cinnamylidene Acetic Acid Derived Crosslinks in Poly(ε-caprolactone) Networks %U https://doi.org/10.1557/opl.2015.494 %X Photoswitchable polymeric materials comprise moieties that undergo light-induced chemical reactions or conformational alteration. The reversibility of photo-responsive molecular switches has an influence on material functions observed on the macroscopic level such as reversibility of shape switching, especially with regard to the number of cycles. Cinnamylidene acetic acid (CAA) has received attention due to its reversible dimerization by [2+2] cycloaddition reactions. In the present study, possible side-reactions during photo-scission of the CAA dimers as netpoints in poly(ε-caprolactone) based materials were studied by fluorescence spectroscopy, HPLC and 1H,1H-COSY. Liberation of fluorescent fragments, which have their origin in the various dimer structures, could only be found in small amounts, while a non-identified species seems to be generated during dimerization and photo-scission. The results furthermore suggest that CAA-based switches in PCL-networks do not provide full reversibility of netpoint formation under the examined conditions, due to non-selective side-reactions, which could lead to an attenuation of the macroscopic effect in multiple photo-cycles. In perspective, the design of CAA derivatives with enhanced photo-reversibility should be targeted. %0 journal article %@ 0021-9797 %A Seiffert, S., Friess, F., Lendlein, A., Wischke, C. %D 2015 %J Journal of Colloid and Interface Science %P 38-42 %R doi:10.1016/j.jcis.2015.04.017 %T Faster Droplet Production by Delayed Surfactant-Addition in Two-Phase Microfluidics to form Thermo-Sensitive Microgels %U https://doi.org/10.1016/j.jcis.2015.04.017 %X Microfluidic droplet templating produces monodisperse particles of well controllable sizes, but this is limited by the necessity to operate microfluidic devices at low flow rates in the dripping regime. Here, the per-channel rate of droplet production could be substantially increased by delayed surfactant addition as applied and verified for microfluidic production of N-isopropylacrylamide based microgels. %0 journal article %@ 1386-0291 %A Fang, L., Wischke, C., Kratz, K., Lendlein, A. %D 2015 %J Clinical Hemorheology and Microcirculation %N 1 %P 77-87 %R doi:10.3233/CH-151934 %T Influence of film thickness on the crystalline morphology of a copolyesterurethane comprising crystallizable poly(Epsilon-caprolactone) soft segments %U https://doi.org/10.3233/CH-151934 1 %X BACKGROUND: In this work a model approach to investigate changes in crystalline morphology during heating/cooling procedures in the context of programming and induction of the shape-memory effect is presented. OBJECTIVE AND METHOD: Atomic-force microscopy (AFM) was performed to investigate the variations in poly(ε-caprolactone) (PCL) crystalline morphology in nm thin films on a silicon substrate and a film with 20 μm thickness, prepared from a copolyesterurethane (named PDLCL) consisting of crystallizable poly(ω-pentadecalactone) (PPDL) hard segments and crystallizable PCL segments forming switching domains. RESULTS: PCL crystals in switching domains melted/recrystallized repeatedly during heating/cooling cycles between 20 and 70°C, while evident variation in PPDL crystals forming hard domains remained was not observed. When film thickness was 20 nm, PCL edge-on lamellae were observed, confined in the phase-separated morphology, while flat-on PCL lamellae, which broke out from the previous phase-separated morphology, were obtained at a film thickness of 170 nm. In contrast, large PCL spherulites were observed in the 20 μm thick film. CONCLUSION: PCL crystalline morphology in PDLCL as well as the competition between crystallization and phase separation can be tailored by the film thickness and the substrate. Such AFM investigations on thin films can be a helpful approach for predicting the crystal morphology in micro-/nanoscaled objects. %0 conference poster %@ %A Jiang, J., Liu, Y., Seifert, B., dal Bianco, A., Wischke, C., Kratz, K., Lendlein, A. %D 2015 %J Design von Biosystemen - Vom fundamentalen Verständnis zu neuen Anwendungen %T Multifunktionale Materialien für die Biotechnologie %U %X %0 journal article %@ 0939-6411 %A Mathew, S., Baudis, S., Neffe, A.T., Behl, M., Wischke, C., Lendlein, A. %D 2015 %J European Journal of Pharmaceutics and Biopharmaceutics A %P 18-26 %R doi:10.1016/j.ejpb.2015.03.025 %T Effect of diisocyanate linkers on the degradation characteristics of copolyester urethanes as potential drug carrier matrices %U https://doi.org/10.1016/j.ejpb.2015.03.025 %X In this study, the effect of three aliphatic diisocyanate linkers, L-lysine diisocyanate ethyl ester (LDI), hexamethylene diisocyanate (HDI), and racemic 2,2,4-/2,4,4-trimethyl hexamethylene diisocyanate (TMDI), on the degradation of oligo[(rac-lactide)-co-glycolide] (64:36 mol%) based polyester urethanes (PEU) was examined. Samples were characterized for their molecular weight, mass loss, water uptake, sequence structure, and thermal and mechanical properties. Compared to non-segmented PLGA, the PEU showed higher water uptake and generally degraded faster. Interestingly, the rate of degradation was not directly correlating with the hydrophilicity of the diisocyanate moieties; instead, competing intra-/intermolecular hydrogen bonds in between urethane moieties appear to substantially decrease the rate of degradation for LDI-derived PEU. By comparing microparticles (μm) and films (mm) as matrices of different dimensions, it was shown that autocatalysis remains a contributor to degradation of the larger-sized PEU matrices as it is typical for non-segmented lactide/glycolide copolymers. The shown capacity of lactide/glycolide-based multiblock copolymers to degrade faster than PLGA and exhibit improved elastic properties could be of interest for medical implants and drug release systems. %0 conference poster %@ %A Wischke, C., Friess, F., Lendlein, A. %D 2015 %J Advanced Functional Polymers for Medicine (AFPM) %T Programming shape changes of shape-memory microparticles towards increased surface areas by elastic recovery of a phantom matrix %U %X %0 conference lecture %@ %A Friess, F., Lendlein, A., Wischke, C. %D 2015 %J MRS Fall Meeting 2015; Symposium H “Multifunctionality in Polymer-Based Materials; Gels and Interfaces” %T Two-Phase Microfluidics with Inviscid Drops: Effects of Total Flow Rate and Delayed Surfactant Addition %U %X %0 journal article %@ 1613-6810 %A Wischke, C., Schossig, M., Lendlein, A. %D 2014 %J Small %N 1 %P 83-87 %R doi:10.1002/smll.201202213 %T Shape-Memory Effect of Micro-/Nanoparticles from Thermoplastic Multiblock Copolymers %U https://doi.org/10.1002/smll.201202213 1 %X The miniaturization and retained full shape-memory functionality with particle switching to different predefined shapes is reported for semi-crystalline multiblock copolymer matrices with all dimensions in the low micrometer-range. A matrix size-induced reduction of crystallinity suggests limitations of functionality in the low nanometer range. Applications as actuators in microdevices or as microcarriers with switchable shapes for modulated biorecognition are suggested. %0 journal article %@ 1042-7147 %A Friess, F., Lendlein, A., Wischke, C. %D 2014 %J Polymers for Advanced Technologies %N 11 %P 1285-1292 %R doi:10.1002/pat.3313 %T Photoinduced synthesis of polyester networks from methacrylate functionalized precursors: analysis of side reactions %U https://doi.org/10.1002/pat.3313 11 %X Polyester networks can be prepared by ultraviolet (UV)-light-induced radical polymerization of methacrylate functionalized oligo(ε-caprolactone)s. The properties and functions of the obtained materials depend on defined network structures and may be altered, if crosslinking would occur by side reactions in other positions than the methacrylate endgroups. In order to explore whether and to which extent such side reactions occur, network synthesis as well as related model reactions were performed in the absence of photoinitiator. Hereby precursor structures (linear and four-arm star-shaped) and reaction conditions (in solution and in the melt) were varied. Unspecific side reactions were found only upon extensive UV irradiation for 60 min (26 mW cm-2) with minor but detectable alterations of physicochemical properties of the networks. The analysis of model reactions suggested minor photolytic cleavage of ester bonds during polymer network synthesis. However, the effect of these side reactions on network properties and functions appeared to be less relevant than an incomplete precursor integration because of a too short UV irradiation for crosslinking. %0 journal article %@ 0939-6411 %A Mathew, S., Lendlein, A., Wischke, C. %D 2014 %J European Journal of Pharmaceutics and Biopharmaceutics %N 2 %P 403-407 %R doi:10.1016/j.ejpb.2014.04.003 %T Characterization of protein-adjuvant coencapsulation in microparticles for vaccine delivery %U https://doi.org/10.1016/j.ejpb.2014.04.003 2 %X Protein antigens encapsulated as vaccines in poly[(rac-lactide)-co-glycolide] (PLGA) microparticle carriers can induce immune responses. The intensity and directions of this response can be controlled by coloading the microparticles with immunomodulatory adjuvants, e.g., muramyl dipeptide (MDP) as adjuvant combined with ovalbumin (Ova) as protein antigen. In this study, methodologies for an individual quantification of both encapsulated substances should be reported, which comprise (i) a separation process to isolate and determine MDP as intact molecule and (ii) a simultaneous degradation of both analytes with subsequent specific quantification of Ova fragments. It was shown that coloading of both substances resulted in a substantially reduced encapsulation efficiency of MDP. This illustrates that correct conclusions on dose–response relationships in future vaccination studies can only be drawn, if a selective method for adjuvant and protein quantification will be applied. %0 conference poster %@ %A Stoermann, F., Wischke, C., Lendlein, A. %D 2014 %J 2014 MRS Fall Meeting & Exhibit %T Photo-Reversibility of Cinnamylidene Acetic Acid Derived Crosslinks in Poly(Epsilon-caprolactone) Networks %U %X %0 journal article %@ 0743-7463 %A Wischke, C., Lendlein, A. %D 2014 %J Langmuir %N 10 %P 2820-2827 %R doi:10.1021/la4025926 %T Method for Preparation, Programming, and Characterization of Miniaturized Particulate Shape-Memory Polymer Matrices %U https://doi.org/10.1021/la4025926 10 %X Their capability to change their shape on demand has created significant interest for shape-memory polymers (SMPs) in minimally invasive surgery. To evaluate the miniaturization of SMP matrices for small-sized implants or controlled release systems, a strategy to prepare and evaluate microsized SMP model particles is required. This methodological study reports the emulsion-based preparation of ∼30 μm microparticles (MPs) from a phase-segregated SMP, poly(ε-caprolactone) [PCL] and poly(ω-pentadecalactone) [PPDL], with a particular focus on the effects of process parameters such as polymer solvents or stabilizer type/concentration on formation and size distribution of SMP MPs. Processes for the preparation of SMP MP-loaded water-soluble polymer films with tailored mechanical properties were developed and applied for programming the SMP MP to a temporary ellipsoid shape by film stretching. For the functional evaluation of shape recovery of MPs, a light microscopy-based setup with temperature control is proposed by which the stimuli-induced switching of the microsized SMP matrices could be confirmed. Overall, by applying this methodological strategy to various thermoplastic SMPs, a routine to identify and characterize the microscale functionality of SMPs in miniaturized applications will be broadly accessible. %0 conference lecture %@ %A Wischke, C., Merino, M., Roch, T., Lendlein, A. %D 2014 %J HVI Workshop, Status Meeting at Makromolekulares Kolloquium 2014 %T Characterizing model particle surfaces with different cellular uptake behaviour %U %X %0 conference lecture %@ %A Wischke, C., Mathew, S., Roch, T., Krueger, A., Lendlein, A. %D 2014 %J BioBarriers 2014 %T Active Particulate Polymer Carriers %U %X %0 journal article %@ 2192-2659 %A Friess, F., Noechel, U., Lendlein, A., Wischke, C. %D 2014 %J Advanced Healthcare Materials %N 12 %P 1986-1990 %R doi:10.1002/adhm.201400433 %T Polymer Micronetworks with Shape-Memory as Future Platform to Explore Shape-Dependent Biological Effects %U https://doi.org/10.1002/adhm.201400433 12 %X Polymer micronetworks allowing stimuli-induced, predefined, and spatially directed shape shifts. The temperature-induced on-demand switching of shape is introduced as a function of polyester carriers. With their adjustable ­switching temperature, micronetworks may serve as a model system to explore static and dynamic shape effects in biological systems. %0 journal article %@ 1433-7851 %A Wei, Q., Becherer, T., Angioletti-Uberti, S., Dzubiella, J., Wischke, C., neffe, A.T., Lendlein, A., Ballauff, M., Haag, R. %D 2014 %J Angewandte Chemie - International Edition %N 31 %P 8004-8031 %R doi:10.1002/anie.201400546 %T Protein Interactions with Polymer Coatings and Biomaterials %U https://doi.org/10.1002/anie.201400546 31 %X Protein adsorption is considered to be the most important factor of the interaction between polymeric biomaterials and body fluids or tissues. Water-mediated hydrophobic and hydration forces as well as electrostatic interactions are believed to be the major factors of protein adsorption. A systematic analysis of various monolayer systems has resulted in general guidelines, the so-called “Whitesides rules”. These concepts have been successfully applied for designing various protein-resistant surfaces and are being studied to expand the understanding of protein–material interactions beyond existing limitations. Theories on the mechanisms of protein adsorption are constantly being improved due to the fast-developing analytical technologies. This Review is aimed at improving these empirical guidelines with regard to present theoretical and analytical advances. Current analytical methods to test mechanistic hypotheses and theories of protein–surface interactions will be discussed. Special focus will be given to state-of-the-art bioinert and biospecific coatings and their applications in biomedicine. %0 conference lecture %@ %A Wischke, C., Weigel, J., Bulavina, L., Lendlein, A. %D 2014 %J 13th European Symposium on Controlled Drug Delivery, ESCDD 2014 %T Sustained release carrier for adenosine triphosphate as signaling molecule %U %X %0 journal article %@ 0168-3659 %A Wischke, C., Weigel, J., Bulavina, L., Lendlein, A. %D 2014 %J Journal of Controlled Release %P 86-91 %R doi:10.1016/j.jconrel.2014.07.047 %T Sustained release carrier for adenosine triphosphate as signaling molecule %U https://doi.org/10.1016/j.jconrel.2014.07.047 %X Adenosine triphosphate (ATP) is a molecule with a fascinating variety of intracellular and extracellular biological functions that go far beyond energy metabolism. Due to its limited passive diffusion through biological membranes, controlled release systems may allow to interact with ATP-mediated extracellular processes. In this study, two release systems were explored to evaluate the capacity for either long-term or short-term release: (i) Poly[(rac-lactide)-co-glycolide] (PLGA) implant rods were capable of ATP release over days to weeks, depending on the PLGA molecular weight and end-group capping, but were also associated with partial hydrolytic degradation of ATP to ADP and AMP, but not adenosine. (ii) Thermosensitive methylcellulose hydrogels with a gelation occurring at body temperature allowed combining adjustable loading levels and the capacity for injection, with injection forces less than 50 N even for small 27G needles. Finally, a first in vitro study illustrated purinergic-triggered response of primary murine microglia to ATP released from hydrogels, demonstrating the potential relevance for biomedical applications. %0 conference poster %@ %A Wischke, C., Merino, M., Roch, T., Krueger, A., Lendlein, A. %D 2014 %J Makromolekulares Kolloquium 2014 %T Copolymer nanoparticles: effects of polymer composition and inflammatory conditions on endocytosis by endothelial cells %U %X %0 conference lecture (invited) %@ %A Wischke, C., Lendlein, A. %D 2014 %J 12. Bionnale 2014 %T Multifunktionale Biomaterialien %U %X %0 journal article %@ 0044-8249 %A Wei, Q., Becherer, T., Angioletti-Uberti, S., Dzubiella, J., Wischke, C., Neffe, A.T., Lendlein, A., Ballauff, M., Haag, R. %D 2014 %J Angewandte Chemie %N 31 %P 8138-8169 %R doi:10.1002/ange.201400546 %T Wechselwirkungen von Proteinen mit Polymerbeschichtungen und Biomaterialien %U https://doi.org/10.1002/ange.201400546 31 %X Die Proteinadsorption gilt als der wichtigste Faktor der Wechselwirkung zwischen polymeren Biomaterialien und Körperflüssigkeiten oder -gewebe. Die Haupteinflussfaktoren auf die Proteinadsorption sind wasservermittelte hydrophobe und Hydratationskräfte sowie elektrostatische Wechselwirkungen. Eine systematische Analyse verschiedener Monolagen führte zur Aufstellung allgemeiner Leitsätze, den sogenannten “Whitesides-Regeln”. Diese Konzepte wurden erfolgreich auf die Entwicklung verschiedener proteinresistenter Oberflächen angewendet und werden kontinuierlich weiterentwickelt, um das Verständnis von Protein-Material-Wechselwirkungen über die bisherigen Grenzen hinaus zu erweitern. Ebenso werden die Theorien zu Proteinadsorptionsmechanismen aufgrund der sich schnell entwickelnden analytischen Technologien fortlaufend verbessert. Ziel dieses Aufsatzes ist die Verbesserung der aufgestellten empirischen Leitlinien im Hinblick auf die theoretischen und analytischen Fortschritte. Dabei werden die aktuellen analytischen Methoden zur Untersuchung mechanistischer Hypothesen und Theorien zu Protein-Oberflächen-Wechselwirkungen besprochen. Ein besonderes Augenmerk liegt auf aktuellen Technologien im Bereich bioinerter und biospezifischer Beschichtungen und ihrer Anwendungen in der Biomedizin. %0 conference lecture %@ %A Wischke, C., Weigel, J., Lendlein, A. %D 2014 %J 2014 MRS Fall Meeting & Exhibit %T Poly(n-butylcyanoacrylate) Nanoparticles as Carriers for Adenosine triphosphate %U %X %0 conference poster %@ %A Wischke, C., Mathew, S., Roch, T., Lendlein, A. %D 2014 %J 9th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology %T Microparticles as carriers for phagocytosis and modulation of immune cells %U %X %0 conference poster %@ %A Wischke, C., Mathew, S., Roch, T., Krueger, A., Lendlein, A. %D 2014 %J BioBarriers 2014 %T Active Particulate Polymer Carriers %U %X %0 conference lecture (invited) %@ %A Lendlein, A., Wischke, C. %D 2014 %J 13th European Symposium on Controlled Drug Delivery, ESCDD 2014 %T Active Polymers and Carriers %U %X %0 conference lecture %@ %A Wischke, C., Loebler, M., Neffe, A.T., Hanh, B.D., Sternberg, K., Stachs, O., Guthoff, R., Lendlein, A. %D 2014 %J Jahrestagung Deutsche Pharmazeutische Gesellschaft 2014 %T A polymeric multifunctional glaucoma implant %U %X %0 conference poster %@ %A Racheva, M., Romero, O., Julich-Gruner, K.K., Ulrich, A.S., Wischke, C., Lendlein, A. %D 2014 %J Advanced Functional Polymers for Medicine, AFPM 2014 %T Purity of tyrosinase as biocatalyst for hydrogels affects the stability of therapeutic peptides %U %X %0 conference lecture %@ %A Friess, F., Lendlein, A., Wischke, C. %D 2014 %J 6th Forum on New Materials: Symposium Smart Polymers for Biomedical Applications, CIMTEC 2014 %T Microparticles from Photocrosslinked Polyesters %U %X %0 conference lecture %@ %A Racheva, M., Julich-Gruner, K.K., Neffe, A.T., Wischke, C., Lendlein, A. %D 2014 %J 2014 MRS Fall Meeting & Exhibit %T Functionalization Degree of Telechelics as a Structural Parameter to Influence the Properties of Enzymatically Formed Polyethylene Glycol Based Networks %U %X %0 conference poster %@ %A Fang, L., Wischke, C., Kratz, K., Lendlein, A. %D 2014 %J Advanced Functional Polymers for Medicine, AFPM 2014 %T Influence of Film Thickness on the Morphology of a Copolyesterurethane Comprising Crystallizable Poly(Epsilon-caprolactone) Segments %U %X %0 conference poster %@ %A Wischke, C., Lendlein, A. %D 2014 %J SPIE BiOS 2014 %T Stimuli-induced, directed actuation of micro/nanaoparticles from a multiblock copolyester urethane %U %X %0 conference lecture %@ %A Wischke, C. %D 2014 %J Vortrag am Berlin-Brandenburger Centrum fuer Regenerative Therapien zum Besuch Prof. Leong %T Biomaterial-based Regenerative Therapies and Carrier Systems %U %X %0 conference poster %@ %A Wischke, C., Neffe, A.T., Loebler, M., Sternberg, K., Stachs, O., Guthoff, R., Lendlein, A. %D 2014 %J 13th European Symposium on Controlled Drug Delivery, ESCDD 2014 %T A polymeric multifunctional glaucoma implant %U %X %0 conference lecture %@ %A Racheva, M., Romero, O., Julich-Gruner, K.K., Ulrich, A.S., Wischke, C., Lendlein, A. %D 2014 %J 2014 MRS Fall Meeting & Exhibit %T Purity of mushroom tyrosinase as a biocatalyst for biomaterial synthesis affects the stability of therapeutic peptides %U %X %0 journal article %@ 1742-5247 %A Wischke, C., Behl, M., Lendlein, A. %D 2013 %J Expert Opinion on Drug Delivery %N 9 %P 1193-1205 %R doi:10.1517/17425247.2013.797406 %T Drug-releasing shape-memory polymers – The role of morphology, processing effects, and matrix degradation %U https://doi.org/10.1517/17425247.2013.797406 9 %X Expert opinion: The combination of SMPs with a drug-release functionality leads to multifunctional carriers that are an interesting technology for pharmaceutical sciences and can be further expanded by new materials such as thermoplastic SMPs or temperature-memory polymers. Experimental studies should include relevant molecules as (model) drugs and provide a thermomechanical characterization also in an aqueous environment, report on the potential effect of drug type and loading levels on the shape-memory functionality, and explore the potential correlation of polymer degradation and drug release. %0 journal article %@ 1022-1360 %A Racheva, M., Julich-Gruner, K.K., Nöchel, U., Neffe, A.T., Wischke, C., Lendlein, A. %D 2013 %J Macromolecular Symposia %N 1 %P 24-32 %R doi:10.1002/masy.201300112 %T Influence of Drying Procedures on Network Formation and Properties of Hydrogels from Functionalized Gelatin %U https://doi.org/10.1002/masy.201300112 1 %X Side chain functionalization of gelatin with tyrosine-derived moieties, desaminotyrosine (DAT) or desaminotyrosyl tyrosine (DATT), has been reported to lead to physical networks stabilized by aromatic interactions and hydrogen bonds, while the inherent ability of gelatin chains to organize in helices is suppressed. Here, the treatment of DAT and DATT gelatin films at defined temperatures (drying at 5 °C, freeze-drying, and freeze-thawing) were explored for the potential to additionally stabilize the hydrogels by increasing the content of helical domains as additional physical netpoints. The influence of the drying procedures on the hydrogel properties such as network morphology and mechanical properties were analyzed by WAXS, swelling, and rheological measurements. The triple helix content had a stabilizing effect on gelatin-based hydrogels at temperatures below the helix-to-coil transition. However, this effect was less pronounced at physiological conditions above the transition temperature, resulting in rapid dissolution of the physical gelatin networks. %0 journal article %@ 1743-4440 %A Neffe, A.T., Wischke, C., Racheva, M., Lendlein, A. %D 2013 %J Expert Review of Medical Devices %N 6 %P 813-833 %R doi:10.1586/17434440.2013.839209 %T Progress in biopolymer-based biomaterials and their application in controlled drug delivery %U https://doi.org/10.1586/17434440.2013.839209 6 %X Biopolymer-based materials are based on re-growing resources and are attractive for biomedical applications, as they can inherently combine degradability in vivo, can offer sites of adhesion for cells and proteins, often show good biocompatibility and may additionally be used to release embedded bioactive molecules. However, their selection and efficient use for specific applications require an understanding of molecular principles and relationships between the molecular and macroscopic level to establish distinct properties and functions. Here, synthetic routes are described, which allow tailoring properties and functions of biopolymer-based materials. The biological evaluation of such materials is discussed, with a special emphasis on their application in controlled release systems such as hydrogels and particulate carriers. %0 journal article %@ 0168-3659 %A Wischke, C., Schneider, C., Neffe, A.T., Lendlein, A. %D 2013 %J Journal of Controlled Release %N 1 %P e 22 %R doi:10.1016/j.jconrel.2013.08.052 %T Sustained release hydrogels by in situ polymerized polyalkylcyanoacrylate coating %U https://doi.org/10.1016/j.jconrel.2013.08.052 1 %X No abstract %0 conference object %@ 1550-6703 %A Friess, F., Lendlein, A., Wischke, C. %D 2013 %J PMSE Preprints %P 3 %T Investigating side-reactions during UV-induced preparation of oligo(epsilon-caprolactone) based shape-memory polymer networks %U %X %0 journal article %@ 1946-4274 %A Friess, F., Lendlein, A., Wischke, C. %D 2013 %J MRS Online Proceedings Library %P 173-178 %R doi:10.1557/opl.2013.815 %T Morphology of crosslinked poly(Epsilon-caprolactone) microparticles %U https://doi.org/10.1557/opl.2013.815 %X In order to explore the feasibility for preparing defined crosslinked particulate structures, oligo(ε-caprolactone) [oCL] derived microparticles (MPs) were crosslinked in non-molten, non-dissolved, i.e. solid state in aqueous suspension by applying a controlled regime with well-defined polymer network precursors either with or without photoinitiator. The MPs (diameter ∼ 40 μm) were prepared by an oil-in-water emulsion process from linear 2oCL or 4-arm star-shaped 4oCL with methacrylate end groups. Crosslinking was initiated by UV-laser irradiation (308 nm) at room temperature. Conversion of methacrylate was monitored by ATR-FTIR spectroscopy and crosslinking was confirmed by a lack of MP dissolution in dichloromethane. In a quantitative evaluation of swelling by dynamic light scattering, higher swelling ratios were detected for particles synthesized with photoinitiator. Wrinkled particle surfaces and distorted particle shapes were observed by light microscopy in the solvent-swollen state and by scanning electron microscopy after deswelling. This work indicated some limitations due to internal inhomogeneity of the MP, but particle crosslinking in solid state was generally possible and may be further improved by higher chain mobility during crosslinking. %0 journal article %@ 0378-5173 %A Heilmann, S., Kuechler, S., Wischke, C., Lendlein, A., Stein, C., Schaefer-Korting, M. %D 2013 %J International Journal of Pharmaceutics %N 1-2 %P 96-102 %R doi:10.1016/j.ijpharm.2013.01.027 %T A thermosensitive morphine-containing hydrogel for the treatment of large-scale skin wounds %U https://doi.org/10.1016/j.ijpharm.2013.01.027 1-2 %X The results of our in vitro study indicate that the thermosensitive poloxamer 407 25 wt.% hydrogel is an appropriate carrier system for the topical application of morphine with regard to sustained drug release and ongoing analgesia. %0 journal article %@ 2280-8000 %A Friess, F., Wischke, C., Behl, M., Lendlein, A. %D 2013 %J Journal of Applied Biomaterials & Functional Materials %N 3 %P 273-279 %R doi:10.5301/JABFM.2012.10372 %T Oligo(Epsilon-caprolactone)-based polymer networks prepared by photocrosslinking in solution %U https://doi.org/10.5301/JABFM.2012.10372 3 %X Purpose: Polymer networks with adjustable properties prepared from endgroup-functionalized oligoesters by UV-crosslinking in melt have evolved into versatile multifunctional biomaterials. In addition to the molecular weight or architecture of precursors, the reaction conditions for crosslinking are pivotal for the polymer network properties. Crosslinking of precursors in solution may facilitate low-temperature processes and are compared here to networks synthesized in melt.
Methods: Oligo(ε-caprolactone)-(z)methacrylate (oCL-(z)IEMA) precursors with a linear (z = di) or a four-armed star-shaped (z = tetra) architecture were crosslinked by radical polymerization in melt or in solution with UV irradiation. The thermal, mechanical, and swelling properties of the polymer networks obtained were characterized.
Results: Crosslinking in solution resulted in materials with lower Young’s moduli (E), lower maximum stress (σmax), and higher elongation at break (εB) as determined at 70 °C. Polymer networks from 8 kDa star-shaped precursors exhibited poor elasticity when synthesized in the melt, but can be established as stretchable materials with a semi-crystalline morphology, a high gel- content, and a high elongation at break when prepared in solution.
Conclusions: The crosslinking condition of methacrylate functionalized precursors significantly affected network properties. For some types of precursors such as star-shaped telechelics, synthesis in solution provided semi-crystalline elastic materials that were not accessible from crosslinking in melt. %0 journal article %@ 1552-4973 %A Trajkovski, B., Petersen, A., Perka, C., Scharnagl, N., Wischke, C., Wagermaier, W., Lendlein, A., Duda, G.N. %D 2013 %J Journal of Biomedical Materials Research B %N 6 %P 950-963 %R doi:10.1002/jbm.b.32900 %T Local drug delivery by personalized, intraoperative custom-made implant coating %U https://doi.org/10.1002/jbm.b.32900 6 %X Local administration of drugs can enhance regeneration, prevent infection, or treat postsurgical pain. If used in conjunction with implants, coating strategies should allow the choice of a drug or combination of drugs, their doses, localization, and release due to intraoperative considerations. Current coating technologies lack the ability for personalized medicine strategies. Here, we describe a new intraoperative strategy for drug delivery that allows a personalized approach as local drug delivery by implant coating. A polyvinylalcohol (PVA) patch provides rapid attachment to implant surfaces by cyanoacrylate (CA) adhesives. The CA polymerization was initiated by water uptake of the patch due to exposure to a humid environment. The coating strength depended on the type of the CA, the time of external pressing load and humidification, the properties of the patch and the implant surface. The CA adhesive penetrated and polymerized within the patch without impeding the bioactivity of the embedded molecules or strongly altering the protein release pattern after attachment to the implant surface. The use of CA in combination with the PVA patch proved to be noncytotoxic in vitro. This technology platform opens the possibility for personalized medicine to locally administer drugs due to intraoperative requirements. %0 conference object %@ %A Friess, F., Lendlein, A., Wischke, C. %D 2013 %J Abstracts of Papers of the American Chemical Society, 245th National Spring Meeting of the American-Chemical-Society %P 312-PMSE %T Investigating Side-reactions During UV-induced Preparation of oligo(E-caprolactone) Based Shape-memory Polymer Networks %U %X No abstract %0 conference poster %@ %A Friess, F., Lendlein, A., Wischke, C. %D 2013 %J 245th National ACS Spring Meeting, Symposium on Stimuli-Responsive Polymers %T Investigating Side-reactions During UV-induced Preparation of oligo(E-caprolactone) Based Shape-memory Polymer Networks %U %X %0 journal article %@ 0168-3659 %A Wischke, C., Schneider, C., Neffe, A.T., Lendlein, A. %D 2013 %J Journal of Controlled Release %N 3 %P 321-328 %R doi:10.1016/j.jconrel.2013.02.013 %T Polyalkylcyanoacrylates as in situ formed diffusion barriers in multimaterial drug carriers %U https://doi.org/10.1016/j.jconrel.2013.02.013 3 %X Polymeric hydrogels typically release their drug payload rapidly due to their high water content and the diffusivity for drug molecules. This study proposes a multimaterial system to sustain the release by covering the hydrogel with a poly(alkyl-2-cyanoacrylate) [PACA]-based film, which should be formed by an in situ polymerization on the hydrogel surface initiated upon contact with water. A series of PACA-hydrogel hybrid systems with increasing PACA side chain hydrophobicity was prepared using physically crosslinked alginate films and hydrophilic diclofenac sodium as model hydrogel/drug system. Successful synthesis of PACA at the hydrogel surface was confirmed and the PACA layer was identified to be most homogeneous for poly(n-butyl-2-cyanoacrylate) on both the micro- and nanolevel. At the same time, the diclofenac release from the hybrid systems was substantially sustained from ~ 1 day for unmodified hydrogels up to > 14 days depending on the type of PACA employed as diffusion barrier. Overall, in situ polymerized PACA films on hydrogels may be widely applicable to various hydrogel matrices, different matrix sizes as well as more complex shaped hydrogel carriers. %0 journal article %@ 0168-3659 %A Wischke, C., Neffe, A.T., Hanh, B.D., Kreiner, C.F., Sternberg, K., Stachs, O., Guthoff, R.F., Lendlein, A. %D 2013 %J Journal of Controlled Release %N 3 %P 1002-1010 %R doi:10.1016/j.jconrel.2013.10.021 %T A multifunctional bilayered microstent as glaucoma drainage device %U https://doi.org/10.1016/j.jconrel.2013.10.021 3 %X Commercial non-degradable glaucoma implants are often associated with undesired hypotony, fibrosis, long term failure, and damage of adjacent tissues, which may be overcome by a multifunctional polymeric microstent for suprachoroidal drainage. This study reports the design and fabrication of such devices with tailorable internal diameters (50–300 μm) by solvent-free, continuous hot melt extrusion from blends of poly[(ε-caprolactone)-co-glycolide] and poly(ε-caprolactone) [PCL]. A spatially directed release was supported by bilayered microstents with an internal drug-free PCL layer, and a quantitative description of release kinetics with diclofenac sodium as model drug was provided. Furthermore, the slow degradation pattern (> 1 year) was analyzed and potential effects of 1–5 wt.% drug loading on material properties were excluded. Translational aspects including sterilization by γ-irradiation on dry ice, in vitro biocompatibility, and in vivo implantation were addressed. The promising results support further functional analysis of long-term in vivo performance and suppression of disadvantageous capsule formation. %0 journal article %@ 0939-6411 %A Wischke, C., Krueger, A., Roch, T., Pierce, B.F., Li, W., Jung, F., Lendlein, A. %D 2013 %J European Journal of Pharmaceutics and Biopharmaceutics %N 2 %P 288-296 %R doi:10.1016/j.ejpb.2013.01.025 %T Endothelial cell response to (co)polymer nanoparticles depending on the inflammatory environment and comonomer ratio %U https://doi.org/10.1016/j.ejpb.2013.01.025 2 %X Endothelial cells lining the lumen of blood vessels serve as a physiological barrier controlling nanoparticle movement from the vasculature into the tissue. For exploring the effect of polymer hydrophilicity on nanoparticle interactions with human umbilical vein endothelial cells (HUVECs) in vitro, a series of monomodal poly[acrylonitrile-co-(N-vinylpyrrolidone)] model nanoparticles with increasing hydrophilicity as related to their increasing content (0–30 mol.%) of N-vinylpyrrolidone (NVP) were synthesized by miniemulsion polymerization. Nanoparticles with a low NVP content were rapidly endocytized into all cells independent from the particle dose with toxic effects only observed at high particle concentrations, while only 10–30% of the cells incorporated particles with ⩾20 mol.% NVP. Since pathologies are often related to inflammation, an inflammatory HUVEC culture condition with IL-1β stimulation has been introduced and suggested to be widely applied for studying nanocarriers, since cellular uptake in this assay was clearly increased for NVP contents ⩾20 mol.%. Importantly, the secretion of functional biological mediators by HUVECs was not relevantly influenced by the nanoparticles for both homeostatic and inflammatory conditions. These findings may motivate concepts for nanocarriers specifically targeted to pathologic regions. Additionally, rapidly endocytized Rhodamin B loaded particles with low NVP content may be explored for cell labeling and tracking. %0 conference lecture %@ %A Roch, T., Schmidt, S., Wischke, C., Mathew, S., Ma, N., Lendlein, A. %D 2013 %J 2013 MRS Spring Meeting and Exhibit %T Modulating dendritic cell responses by particulate carriers loaded with NOD receptor agonits %U %X %0 journal article %@ 1946-4274 %A Schmidt, S., Roch, T., Mathew, S., Ma, N., Wischke, C., Lendlein, A. %D 2013 %J MRS Online Proceedings Library %P 179-184 %R doi:10.1557/opl.2013.816 %T Correlating the Uptake and Dendritic Cell Activation by MDP-loaded Microparticles %U https://doi.org/10.1557/opl.2013.816 %X Polymer-based, degradable microparticles (MP) are attractive delivery vehicles for vaccines as the polymer properties can be specifically tailored and the carrier can be loaded with adjuvant. For all newly developed carrier systems it is important to analyze cellular uptake efficiency and the specific effects mediated by the encapsulated agent when phagocytosed by the cells, which is barely reported so far. By the encapsulation of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) labeled with fluoresceinisothiocyanat (FITC) in poly[(rac-lactide)-co-glycolide] (PLGA) MP, the MP was fluorescent and used to visualize the phagocytic uptake. Since encapsulated MDP can activate dendritic cells (DC) via the cytosolic nucleotide-binding oligomerization domain receptors (NOD), it can be investigated whether only cells that have phagocytosed the MP are activated or whether bystander effects occur, resulting in activation of cells, which did not take up MDP-FITC loaded MP. Here, it is demonstrated that increasing MP concentrations in the culture medium had no impact on the viability of DC and that the MP uptake efficiency was dose dependent. Interestingly, it could be shown by the CD86 expression, that only DC, which had engulfed MP, were significantly stronger activated than DC, which had not phagocytosed MDP-FITC loaded MP. On the one hand these results indicate that sufficient amounts of MDP were released from the PLGA carriers into the cytosol of the DC. On the other hand, based on the correlation of uptake and activation on the single cell level, minimal MP induced bystander effects may be expected forin vivo applications. %0 conference lecture (invited) %@ %A Wischke, C., Lendlein, A. %D 2013 %J World Congress on Regenerative Medicine 2013 %T Multifunctional Biomaterials %U %X %0 conference lecture %@ %A Wischke, C., Roch, T., Merino, M., Krueger, A., Li, W., Lendlein, A. %D 2013 %J 12th International Conference on Polymers for Advanced Technologies, PAT 2013 %T Exploring mechanisms of material-mediated nanoparticle uptake by endothelial cells %U %X %0 conference lecture %@ %A Wischke, C., Krueger, A., Roch, T., Lendlein, A. %D 2013 %J Jahrestagung der Deutschen Pharmazeutischen Gesellschaft 2013 %T Polymer-dependent endocytosis kinetics of nanoparticles and relevance of environmental conditions %U %X %0 conference poster %@ %A Stoermann, F., Roch, T., Wischke, C., Lendlein, A. %D 2013 %J 12th International Conference on Polymers for Advanced Technologies, PAT 2013 %T Microcapsules with an aqueous core for protein encapsulation %U %X %0 conference poster %@ %A Racheva, M., Julich-Gruner, K., Noechel, U., Neffe, A.T., Wischke, C., Lendlein, A. %D 2013 %J Advanced Functional Polymers for Medicine, 533th WE-Heraeus-Seminar %T Influence of drying procedures on network properties of physical gelatin hydrogels %U %X %0 conference poster %@ %A Friess, F., Lendlein, A., Wischke, C. %D 2013 %J 12th International Conference on Polymers for Advanced Technologies, PAT 2013 %T Specific and unspecific photoinitiated radical crosslinking reactions of methacrylate functionalized oligo(Epsilon-caprolactone) %U %X %0 conference poster %@ %A Mathew, S., Wischke, C., Roch, T., Lendlein, A. %D 2013 %J 12th International Conference on Polymers for Advanced Technologies, PAT 2013 %T Microparticulate carriers for modulating immune responses %U %X %0 conference lecture %@ %A Wischke, C., Neffe, A.T., Ruesten-Lange, M.v., Braune, S., Luetzow, K., Roch, T., Richau, K., Jung, F., Lendlein, A. %D 2013 %J 12th International Conference on Polymers for Advanced Technologies, PAT 2013 %T The Suitability of Polyethers to Reduce Protein Adsorption and to Improve Hemocompatibility %U %X %0 conference poster %@ %A Wischke, C., Lendlein, A. %D 2013 %J Biotechnologie 2020 plus, 4. Jahreskongress zur BMBF-Initiative %T Multifunktionale Materialien fuer die Biotechnologie %U %X %0 journal article %@ 0008-6215 %A Tripodo, G., Wischke, C., Neffe, A.T., Lendlein, A. %D 2013 %J Carbohydrate Research %P 59-63 %R doi:10.1016/j.carres.2013.08.018 %T Efficient synthesis of pure monotosylated beta-cyclodextrin and its dimers %U https://doi.org/10.1016/j.carres.2013.08.018 %X 6-O-Monotosyl-β-cyclodextrin (mono-Ts-βCD) is one of the most important intermediates in the production of substituted βCD. So far, performing the monotosylation reaction and, in particular, the purification steps was challenging, relied on toxic solvents, and resulted in long and expensive procedures at, importantly, low yields. Here, the reaction of cyclodextrin with p-toluenesulfonyl chloride in aqueous environment is described to obtain a highly pure mono-Ts-βCD, for which a single-step purification with a cation exchange resin was applied. With this synthetic route and purification, yields could be increased from typically <10–15% to 35%, and organic solvents could be avoided. As characterized by FTIR, mass spectrometry, elemental analysis, and NMR, mono-Ts-βCD was obtained with a molar purity of >98 mol %. From mono-Ts-βCD, β-cyclodextrin dimers linked by ethylenediamine (bis-Et-βCD) were successfully prepared (yield 93%, purity 96 mol %) in a one-step approach using an anion exchange resin to trap leaving groups that typically interfere in the reaction. This synthesis procedure with a direct collection of side-products may be a general strategy applicable for nucleophilic substitution of tosylated cyclodextrins. %0 conference lecture %@ %A Santan, H., Wischke, C., Neffe, A., Lendlein, A. %D 2013 %J HVI Method Workshop 2013 %T Protein Adsorption to Synthetic Polymers %U %X %0 journal article %@ 1386-0291 %A Krueger, A., Goers, J., Zaupa, A., Loewenberg, C., Pierce, B.F., Wischke, C., Neffe, A.T., Jung, F., Lendlein, A. %D 2013 %J Clinical Hemorheology and Microcirculation %N 1 %P 133-142 %R doi:10.3233/CH-131697 %T Influence of physically crosslinked gelatins on the vasculature in the avian chorioallantoic membrane %U https://doi.org/10.3233/CH-131697 1 %X Gelatins functionalized with desaminotyrosine (DAT) or desaminotyrosyl tyrosine (DATT) form physically crosslinked hydrogels, due to the interactions between the introduced aromatic moieties and gelatin triple helices, whose extent depends on the thermal treatment of the material. The G-modulus of these hydrogels can be tailored to the range of the natural extracellular matrix by adjusting the degree of crosslinking. While these gelatin-based materials have been shown to be not angiogenic, the aim of the study was to evaluate whether these biomaterials influence the regulation of blood vessels when positioned on the chorionallantoic membrane (CAM) of fertilized eggs. The results clearly indicate that the DAT-functionalized gelatin led to an increase of the diameter of the blood vessels in the CAM, which at the same time is probably associated with an increased blood flow in these CAM vessels. The vessel diameters of the four groups (DAT-functionalized gelatin, DATT-functionalized gelatin, plain gelatin, control group without gelatin, each n = 10) differed significantly (p < 0.0001). Vessels in the CAM exposed to the DAT-functionalized gelatin showed with 36.4 μm ± 3.4 μm the largest mean diameters compared to the mean diameters of the samples exposed to DATT gelatin (16.0 μm ± 0.8 μm; p < 0.05) and the plain gelatin (21.2 μm ± 1.0 μm; p < 0.05), which both did not differ significantly from the vessels of the control group. The biocompatibility of the materials in vitro motivates the exploration of their application as matrix in local drug-release systems with short half-life times (one hour up to several days). %0 conference lecture %@ %A Wischke, C., Friess, F., Lendlein, A. %D 2013 %J 2013 MRS Spring Meeting and Exhibit, Symposium MM – Advanced Materials for Biological and Biomedical Applications %T Morphology of crosslinked poly(Epsilon-caprolactone) particles %U %X %0 conference lecture (invited) %@ %A Wischke, C., Lendlein, A. %D 2012 %J 4th International Conference on Smart Materials, Structures and Systems, CIMTEC 2012 %T Shape-Memory Polymers as Drug Carrier – Points to be considered %U %X %0 conference poster %@ %A Wischke, C., Mathew, S., Roch, T., Frentsch, M., Lendlein, A. %D 2012 %J 12th European Symposium on Controlled Drug Delivery, ESCDD 2012 %T Potential of NOD Ligands as Immune Modulators in Particulate Vaccine Carriers %U %X %0 conference lecture %@ %A Behl, M., Lendlein, A., Wischke, C. %D 2012 %J 9th World Biomaterials Congress %T Triple-functional polymer-based biomaterials combining controlled drug release, degradability and shape-memory capability %U %X %0 book part %@ %A Wischke, C., Schwendeman, S. %D 2012 %J Fundamentals and Applications of Controlled Release Drug Delivery %P 171-228 %R doi:10.1007/978-1-4614-0881-9 %T Degradable polymeric carriers for parenteral controlled drug delivery %U https://doi.org/10.1007/978-1-4614-0881-9 %X treatment for the patient and/or marketing strategies, to name only two. %0 conference lecture %@ %A Wischke, C., Mathew, S., Roch, T., Frentsch, M., Lendlein, A. %D 2012 %J Jahrestagung der Deutschen Pharmazeutischen Gesellschaft 2012 %T Modulating immune responses of human cells by adjuvant loaded particulate carriers %U %X %0 conference lecture %@ %A Wischke, C., Schossig, M., Lendlein, A. %D 2012 %J Materials Science and Engineering, MSE 2012 %T Microscopic characterization of particulate SMP matrices %U %X %0 journal article %@ 0168-3659 %A Wischke, C., Mathew, S., Roch, T., Frentsch, M., Lendlein, A. %D 2012 %J Journal of Controlled Release %N 3 %P 299-306 %R doi:10.1016/j.jconrel.2012.06.034 %T Potential of NOD receptor ligands as immunomodulators in particulate vaccine carriers %U https://doi.org/10.1016/j.jconrel.2012.06.034 3 %X Microparticles have been intensively explored as next generation vaccine carriers in the last decade. They were mostly loaded with toll-like receptor ligands as adjuvants, which are not finally rated for their safety profile. Here, ligands of cytosolic receptors sensing nucleotide and oligomerization domains (NOD) were explored as alternative adjuvants in combination with immunologically inert particulate carriers from poly[(rac-lactide)-co-glycolide], which were shown to be capable to coencapsulate protein antigens as well as γ-d-glutamyl-meso-diaminopimelic acid (iE-DAP) and N-acetylmuramyl‐l-alanyl‐d-isoglutamine (MDP) as NOD receptor agonists. For selectively studying the immunomodulatory potency of the adjuvants rather than of potential immunogenic impurities and for providing a strategy for quality control of future particulate vaccines, the purity of the microparticles was confirmed with different reporter cell lines selectively expressing specific pathogen recognition receptors. Microencapsulated NOD ligands but not blank microparticles were shown to induce a dose-dependent maturation of human monocyte-derived dendritic cells to a proinflammatory phenotype with high levels of released cytokines particularly for iE-DAP. These data suggest their further exploration in vivo. %0 conference lecture (invited) %@ %A Lendlein, A., Wischke, C., Mathew, S., Roch, T., Kratz, K. %D 2012 %J 12th European Symposium on Controlled Drug Delivery, ESCDD 2012 %T Multifunctional Polymer-based Carrier Systems %U %X %0 journal article %@ 1946-4274 %A Wischke, C., Steuer, S., Lendlein, A. %D 2012 %J MRS Online Proceedings Library %P 31-36 %R doi:10.1557/opl.2012.224 %T Determining loading kinetics of drug releasing degradable shape-memory polymers %U https://doi.org/10.1557/opl.2012.224 %X Modern concepts for biofunctional implants often comprise the controlled release of bioactive compounds to gain specific biofunctionalities. Here, amorphous and semi-crystalline copolyester-based shape-memory polymer (SMP) networks are reported as matrix for pharmaceutical applications. Drug loading of such crosslinked networks by swelling techniques requires tools to determine the actual payload. In this report, the capability of determining loading kinetics by mass increase or changes of drug concentration in the swelling medium is explored for two types of copolyester-based SMP networks differing in their crosslinking chemistry. Nitrofurantoin and ethacridine lactate served as hydrophobic and hydrophilic model drugs. It was found, that the absolute values of the determined payload did not systematically agree with those obtained by the more reliable technique of network cleavage and spectrophotometric quantification. However, the studies indicate that for both types of SMP materials and both drugs, maximum incorporation of the drugs occurred within a few hours. The time until equilibration depended on the network properties. %0 conference lecture %@ %A Wischke, C., Lendlein, A. %D 2012 %J RMIB Beiratssitzung, Forschungsarbeiten im BCRT %T Polymer based biomaterials %U %X %0 conference poster %@ %A Wischke, C., Schneider, C., Neffe, A.T., Lendlein, A. %D 2012 %J 2nd Symposium on Innovative Polymers for Controlled Delivery, SIPCD 2012 %T Sustained release hydrogels by in situ polymerized coating with polyalkylcyanoacrylates %U %X %0 conference lecture %@ %A Mathew, S., Roch, T., Frentsch, M., Wischke, C., Lendlein, A. %D 2012 %J Advanced Functional Polymers for Medicine, AFPM 2012 %T Adjuvant effect of microencapsulated NOD ligands studied in a human phagocytic cell line %U %X %0 conference poster %@ %A Pierce, B.F., Li, W., Scharnagl, N., Wischke, C., Sisson, A., Lendlein, A. %D 2012 %J Advanced Functional Polymers for Medicine, AFPM 2012 %T Influence of the co-monomer ratio on the physical properties and cytotoxicity of poly[acrylonitrile-co-(N-vinylpyrrolidone)]-based nanoparticles %U %X %0 conference poster %@ %A Friess, F., Wischke, C., Behl, M., Lendlein, A. %D 2012 %J Advanced Functional Polymers for Medicine, AFPM 2012 %T Oligo(Epsilon-caprolactone)-based polymer networks prepared by photocrosslinking in solution %U %X %0 conference paper %@ %A Wischke, C., Steuer, S., Lendlein, A. %D 2012 %J MRS Symposium Proceedings, Multifunctional Polymer-Based Materials, 2011 MRS Fall Meeting %P 207-212 %T Determining loading kinetics of drug releasing degradable shape-memory polymers %U %X %0 journal article %@ 2280-8000 %A Li, W., Pierce, B.F, Scharnagl, N., Wischke, C., Sisson, A.L., Lendlein, A. %D 2012 %J Journal of Applied Biomaterials & Functional Materials %N 3 %P 308-314 %R doi:10.5301/jabfm.2012.10430 %T Influence of co-monomer ratio on the chemical properties and cytotoxicity of poly[acrylonitrile-co-(N-vinylpyrrolidone)] nanoparticles %U https://doi.org/10.5301/jabfm.2012.10430 3 %X Purpose. A system of nanoparticles with varying hydrophilicities may include promising biomaterial candidates as they offer various cellular uptake properties and a range of drug encapsulation efficacies, which would be advantageous in regenerative therapies. Therefore, a model system of nanoparticles with varying hydrophilicities was synthesized and assessed for its candidacy as a biomaterial.Methods. Here, acrylonitrile (AN) was copolymerized with N-vinylpyrrolidone (NVP) in a mini-emulsion to form a family of nanoparticles, thereby enabling the systematic variation of the copolymer hydrophilicity. The nanoparticles based on these copolymers were prepared and characterized using 1H-NMR, dynamic light scattering, differential scanning calorimetry, and thermal gravimetric analysis. Finally, the cytotoxicity of the nanoparticles was assessed by conducting indirect tests using L929 fibroblasts.
Results. The nanoparticles showed well controlled NVP/AN molar ratios as determined by 1H NMR, well defined diameters ranging from approximately 100 nm to 200 nm, and increasing glass transition temperatures with increasing molar NVP content. Finally, L929 fibroblasts only slightly changed their morphology upon incubation with material eluates.
Conclusions. Poly[acrylonitrile-co-(N-vinylpyrrolidone)] nanoparticles with varying amounts of NVP were shown to be a promising model system for further biological assessment. %0 journal article %@ %A Wischke, C., Kratz, K., Jung, F., Lendlein, A. %D 2012 %J BioTOPics : Journal of Biotechnology in Berlin-Brandenburg %P 5-7 %T Helmholtz Virtual Institute „Multifunctional Materials for Medicine“ %U %X into the regional cluster “Healthcare Industry Berlin-Brandenburg – Health Capital”. %0 conference paper %@ %A Tripodo, G., Wischke, C., Lendlein, A. %D 2012 %J MRS Symposium Proceedings, Multifunctional Polymer-Based Materials, 2011 MRS Fall Meeting %P 21-28 %T Design of semi-interpenetrating networks based on poly(ethyl-2-cyanoacrylate) and oligo(ethyleneglycol) diglycidyl ether %U %X %0 journal article %@ 2280-8000 %A Mathew, S., Roch, T., Frentsch, M., Lendlein, A., Wischke, C. %D 2012 %J Journal of Applied Biomaterials & Functional Materials %N 3 %P 229-236 %R doi:10.5301/JABFM.2012.10438 %T Adjuvant effect of microencapsulated NOD ligands studied in a human phagocytic cell line %U https://doi.org/10.5301/JABFM.2012.10438 3 %X Background: Modern subunit vaccines, which are of high purity compared with traditional vaccines, are often incapable of inducing strong immune responses as necessary to build an immunological memory. The desired level of immune response can be achieved only by codelivering immune-modulating agents along with the antigenic epitopes present in these high-purity formulations. This study aimed to explore the adjuvant effect of nucleotide oligomerization domain (NOD) receptor agonists as immunomodulators encapsulated in polymeric microparticles as carriers.
Methods: Microparticles (MP) prepared from poly[(rac-lactide)-co-glycolide] (PLGA) (Mn = 5 kDa, PD = 3.2) by the water-in-oil-in-water (w/o/w) emulsion/solvent evaporation technique were characterized in terms of size, surface morphology, payload and endotoxin content. As NOD agonists, N-acetylmuramyl–L-alanyl–D-isoglutamine (MDP; NOD 2) and γ-D-glutamyl-meso-diaminopimelic acid (iE-DAP; NOD 1) were encapsulated. The immunomodulatory potential of these ligand-loaded MP was evaluated with a human acute monocytic leukemia cell line (THP-1X Blue-CD14 cells). 
Results: The MP prepared had a phagocytosable size (<10 µm) with a unimodal size distribution and low endotoxin content (<0.5 EU/mL). A dose-dependent cell activation could be established for MDP-loaded microparticles.
Conclusions: MP with suitable characteristics for phagocytosis can be prepared and loaded with NOD agonists. The capability of these ligand-loaded microparticles to activate monocytes suggests their broader exploration as vaccine carriers. %0 conference lecture %@ %A Wischke, C., Lendlein, A. %D 2012 %J 5. Treffpunkt Regenerative Medizin %T Forschungsfeld B - Polymerbasierte Biomaterialien %U %X %0 conference lecture (invited) %@ %A Lendlein, A., Wischke, C. %D 2012 %J 2nd Symposium on Innovative Polymers for Controlled Delivery, SIPCD 2012 %T Multifunctional Polymer-based Drug Delivery Systems %U %X %0 journal article %@ 1022-1360 %A Mathew, S., Lendlein, A., Wischke, C. %D 2011 %J Macromolecular Symposia %N 1 %P 123-133 %R doi:10.1002/masy.201100059 %T Degradation Behavior of Porous Copolyester Microparticles in the Light of Dynamic Changes in Their Morphology %U https://doi.org/10.1002/masy.201100059 1 %X The pore structures of microparticulate drug carriers are important diffusion pathways, which are not a static property but rather may be changing in the case of degradable matrix polymers such as poly[(rac-lactide)-co-glycolide] (PLGA). In this study, the mutual impacts of dynamic changes in microparticle porosity and polymer degradation were analyzed for PLGA with different molecular weights and end groups as well as PLGA-based triblock copolymers. In selected cases, particularly for PLGA with hydrophilic end groups and low initial number average molecular weight of 5 kDa, pore opening/pore closing phenomena were detected during incubation in phosphate buffer at 37 °C. Initially, pore closing was induced by water-induced plasticization and the reduction of interfacial tension. The pattern of molecular weight decrease and mass loss suggested that pore closing did not result in undesired autocatalytic acceleration of degradation or delayed mass loss due to trapped acidic degradation products. %0 conference lecture %@ %A Wischke, C., Steuer, S., Lendlein, A. %D 2011 %J MRS Fall 2011 Meeting, Symposium V %T Determining loading kinetics of drug releasing degradable shape-memory polymers %U %X %0 conference poster %@ %A Tripodo, G., Wischke, C., Lendlein, A. %D 2011 %J MRS Fall 2011 Meeting, Symposium V %T Design of semi-interpenetrating networks based on poly(ethyl-2-cyanoacrylate) and oligo(ethyleneglycol) diglycidyl ether %U %X %0 conference poster %@ %A Mathew, S., Wischke, C., Lendlein, A. %D 2011 %J Advanced Functional Polymers for Medicine, AFPM 2011 %T Degradation behaviour of porous co-polyester microparticles in the light of dynamic changes in their morphology %U %X %0 book part %@ %A Lendlein, A., Wischke, C., Kratz, K., Heuchel, M., Zotzmann, J., Hiebl, B., Neffe, A., Behl, M. %D 2011 %J Comprehensive Biomaterials %P 479-496 %T Shape- Memory Polymers %U %X Medical devices such as implants, surgical instruments, extracorporal devices or wound covers, as well as controlled drug delivery systems (CDDS) require a specific combination of material properties and functions including, e.g., mechanical stability, biocompatibility, or biofunctionality. Polymeric biomaterials are of high relevance for such applications, as properties and functions can be tuned in a wide range by only small defined variations of their chemical or morphological structure. The rapid progress in surgical techniques, especially in minimally-invasive surgery, requires smart materials, which are capable of an active on-demand movement and which do not need to be removed in a second surgery. These challenges can be addressed by shape-memory polymers (SMPs) described in this chapter. SMPs are of high technological significance for biomedical applications as they enable on demand predefined changes in the shape of a device upon exposure to a suitable stimulus. Multifunctional materials are obtained when the shape-memory effect is combined with an additional function such as hydrolytic degradability, biofunctionality, and controlled drug release. Selected biomaterials with shape-memory capability are presented, including data on their biocompatibility. The potential of SMPs as a platform technology for biomedical applications is sketched by an overview on SMP-based medical devices being developed and the potential use of SMPs as matrix for CDDS. %0 report part %@ %A Wischke, C., Lendlein, A. %D 2011 %J Technologiereport - Regenerative Medizin in Berlin-Brandenburg %N 3 %P 80-82 %T Systeme zur kontrollierten Wirkstofffreisetzung %U 3 %X %0 conference poster %@ %A Tripodo, G., Wischke, C., Neffe, A.T., Lendlein, A. %D 2011 %J Advanced Functional Polymers for Medicine, AFPM 2011 %T Highly elastic poly(ethyl-2-cyanoacrylate) based materials obtained by incorporation of oligo(ethylene glycol) diglycidyl ether as a softener %U %X %0 journal article %@ 1946-4274 %A Tripodo, G., Wischke, C., Lendlein, A. %D 2011 %J MRS Online Proceedings Library %P 25-30 %R doi:10.1557/opl.2012.223  %T Design of semi-interpenetrating networks based on poly(ethyl-2-cyanoacrylate) and oligo(ethyleneglycol) diglycidyl ether %U https://doi.org/10.1557/opl.2012.223  %X The synthesis of semi-interpenetrating networks (SIPN) based on linear poly(ethyl 2-cyanoacrylate) (PECA) and oligo(ethylene glycol) diglycidyl ether (OEGDG) based polymer networks was motivated by the hypothesis that the brittleness of polycyanoacrylates may be overcome by incorporating them into a polymer network architecture. A sequential synthetic route was applied, in which first PECA was prepared by anionic polymerization. Subsequently, OEGDG was crosslinked with different anhydrides and curing catalysts to form networks with hydrolyzable ester bonds and interpenetrating PECA. These SIPNs showed a low water uptake compared to other polyether based networks. Some of the obtained materials were transparent and exhibited a great flexibility, which was maintained also after 24 h of immersion in water and subsequent drying. Such networks could be components of future stimuli-sensitive material systems. %0 journal article %@ 0391-3988 %A Kohl, Y., Kaiser, C., Bost, W., Stracke, F., Thielecke, H., Wischke, C., Lendlein, A., Kratz, K., Lemor, R. %D 2011 %J The International Journal of Artificial Organs %N 2 %P 249-252 %R doi:10.5301/IJAO.2011.6405 %T Near-infrared dye-loaded PLGA nanoparticles prepared by spray drying for photoacoustic applications %U https://doi.org/10.5301/IJAO.2011.6405 2 %X Conclusion: The high optical absorption at the relevant NIR-wavelength around 800 nm in combination with absence of cytotoxicity qualifies the ICG-loaded PLGA particles as promising candidates for degradable photoacoustic contrast agents. %0 journal article %@ 1549-9634 %A Kohl, Y., Kaiser, C., Bost, W., Stracke, F., Fournelle, M., Wischke, C., Thielecke, H., Lendlein, A., Kratz, K., Lemor, R. %D 2011 %J Nanomedicine: Nanotechnology, Biology and Medicine %N 2 %P 228-237 %R doi:10.1016/j.nano.2010.07.006 %T Preparation and Biological Evaluation of Multifunctional PLGA-Nanoparticles designed for Photoacoustic Imaging %U https://doi.org/10.1016/j.nano.2010.07.006 2 %X The excellent photoacoustic properties in combination with the positive biological results qualify the dye-loaded PLGA particles as promising candidates for a resorbable photoacoustic contrast system. %0 conference lecture (invited) %@ %A Lendlein, A., Neffe, A., Wischke, C. %D 2011 %J 3rd International Conference on Smart Materials and Nanotechnology in Engineering, SMN 2011 %T Shape-memory Polymers as Platform Technology for Multifunctional Materials %U %X %0 conference lecture %@ %A Scharnagl, N., Wischke, C., Lendlein, A. %D 2011 %J Medica 2011 %T Berlin-Brandenburg Center for Regenerative Therapies – BCRT, Polymer-based Biomaterials %U %X %0 journal article %@ 1616-5187 %A Wischke, C., Tripodo, G., Choi, N.-Y., Lendlein, A. %D 2011 %J Macromolecular Bioscience %N 12 %P 1637-1646 %R doi:10.1002/mabi.201100226 %T Hydrolytic Degradation Behavior of Poly(rac-lactide)-block-poly(propylene glycol)-block-poly(rac-lactide) Dimethacrylate Derived Networks Designed for Biomedical Applications %U https://doi.org/10.1002/mabi.201100226 12 %X For polymer-based degradable implants, mechanical performance and degradation behavior need to be precisely controlled. Based on a rational design, this work comprehensively describes the properties of photo-crosslinked polymer networks prepared from poly(rac-lactide)-block-poly(propylene glycol)-block-poly(rac-lactide) dimethacrylate precursors during degradation. By varying the length of poly(rac-lactide) blocks connected to a central 4 kDa polyether block, microphase separated networks with adjustable crosslinking density, hydrophilicity/hydrophobicity ratio, thermal, and mechanical properties are obtained. The materials are characterized by a low water uptake, controlled mass loss, and slowly decreasing wet-state E moduli in the kPa range. %0 journal article %@ 1743-4440 %A Lendlein, A., Wischke, C. %D 2011 %J Expert Review of Medical Devices %N 5 %P 533-537 %R doi:10.1586/erd.11.39 %T How to accelerate biomaterial development? Strategies to support the application of novel polymer-based biomaterials in implantable devices %U https://doi.org/10.1586/erd.11.39 5 %X No abstract %0 conference lecture %@ %A Scharnagl, N., Wischke, C., Lendlein, A. %D 2011 %J 6. BMBF-Projektforum Biotechnologie, BIOTECHNICA 2011 %T Berlin-Brandenburg Center for Regenerative Therapies – BCRT, Polymer-based Biomaterials %U %X %0 journal article %@ 1022-1360 %A Wischke, C., Loebler, M., Neffe, A.T., Hanh, B.D., Zierke, M., Sternberg, K., Schmitz, K.-P., Guthoff, R., Lendlein, A. %D 2011 %J Macromolecular Symposia %N 1 %P 59-67 %R doi:10.1002/masy.201100050 %T A Blend of Poly(Epsilon-caprolactone) and Poly[(Epsilon-caprolactone)-co-glycolide] with Remarkable Mechanical Features and Wide Applicability as Biomaterial %U https://doi.org/10.1002/masy.201100050 1 %X Hydrolytic degradation of poly(ε-caprolactone) [PCL] can be enhanced by introduction of 8 wt.% glycolide leading to poly[(ε-caprolactone)-co-glycolide] (PCG), which has a low elongation at break εB of 4%. PCG/PCL blends (50/50 w/w) combined the advantageous features of its individual components such as mechanical properties similar to pure PCL (εB, Blend: 900 ± 230%; εB, PCL: 730 ± 50 at 20 °C), water uptake rates during degradation similar to pure PCG, and linear mass loss during bulk degradation independent from sample dimensions. The outcome of cytotoxicity studies was depending on the cell type with promising results, e.g., for Tenon fibroblasts. Easy processing of the blend was demonstrated by melt compression, foaming with CO2, and hot melt extrusion, suggesting a wide applicability as biomaterial, e.g., as drug carrier. %0 conference poster %@ %A Wischke, C., Tripodo, G., Choi, N.-Y., Lendlein, A. %D 2011 %J Advanced Functional Polymers for Medicine, AFPM 2011 %T Design of poly(rac-lactide)-b-poly(propylene glycole)-b-poly(rac-lactide) dimethacrylate derived networks as degradable materials for biomedical application %U %X %0 conference lecture %@ %A Wischke, C., Lendlein, A. %D 2011 %J MRS Fall 2011 Meeting %T Design aspects for drug releasing degradable shape-memory polymers %U %X %0 conference lecture (invited) %@ %A Wischke, C. %D 2011 %J Multifunctional Biomaterials and Polymer-based Controlled Drug Release Systems, 2nd Sino-German Symposium %T Polymer-based glaucoma implants %U %X %0 journal article %@ 1386-0291 %A Wischke, C., Lendlein, A. %D 2011 %J Clinical Hemorheology and Microcirculation %N 1-4 %P 347-355 %R doi:10.3233/CH-2011-1485 %T Designing multifunctional polymers for cardiovascular implants %U https://doi.org/10.3233/CH-2011-1485 1-4 %X Polymer-based biomaterials are extensively used in all disciplines of clinical medicine and innovations in biomaterial science are building a product pipeline, e.g., of future cardiovascular implants. Still, cardiovascular applications demand a number of extensive requirements of properties and functions to be fulfilled by the polymer matrix. This report provides an overview on some of these issues and how they can be addressed by a tailored design of novel polymer-based biomaterials. Multifunctional shape-memory polymers are highlighted as a class of materials that combine biocompatibility and the capability for stimuli-induced active movements for anchoring of implants with a controlled degradation and drug release profile to enable a functional regeneration of the tissue at the application site. %0 conference poster %@ %A Wischke, C., Loebler, M., Neffe, A.T., Hanh, B.D., Zierke, M., Sternberg, K., Schmitz, K.-P., Guthoff, R., Lendlein, A. %D 2011 %J Advanced Functional Polymers for Medicine, AFPM 2011 %T A Blend of Poly(Epsilon-caprolactone) and Poly[(Epsilon-caprolactone)-co-glycolide] with Remarkable Mechanical Features and Wide Applicability as Biomaterial %U %X %0 journal article %@ 1022-1360 %A Tripodo, G., Wischke, C., Lendlein, A. %D 2011 %J Macromolecular Symposia %N 1 %P 49-58 %R doi:10.1002/masy.201100058 %T Highly Flexible Poly(ethyl-2-cyanoacrylate) Based Materials Obtained by Incorporation of Oligo(ethylene glycol)diglycidylether %U https://doi.org/10.1002/masy.201100058 1 %X Poly(ethyl-2-cyanoacrylate) (PECA) is a polymer with potential medical or technical applications, which are limited due to its high brittleness. In this work, the capability of different ethylene or propylene glycol-based oligomers to provide flexible poly(ethyl-2-cyanoacrylate) films upon blending is analyzed. The used oligoethers have been chosen with different end groups or lateral substituents and their effects the on macroscopic behavior of the obtained materials have been characterized. During its synthesis, in situ blending of PECA was performed with increasing quantities of oligo(ethylene glycol) diglycidyl ether providing homogeneously miscible materials with single Tg's. The Tg's decreased in a concentration dependent manner and showed negative deviation from predictions by the Fox equation, possibly due to specific intermolecular interactions. Remarkably, the mechanical properties could be tailored over a wide range with Young's moduli of 0.2 to 900 MPa, which so far has not been reported for cyanoacrylate-based materials. Therefore, the concept of compatible blends should be further explored to establish flexible cyanoacrylate-based materials for various technical or biomedical applications. %0 conference poster %@ %A Tripodo, G., Wischke, C., Lendlein, A. %D 2011 %J Advanced Functional Polymers for Medicine, AFPM 2011 %T Highly Flexible Poly(ethyl-2-cyanoacrylate) Based Materials Obtained by Incorporation of Oligo(ethylene glycol)diglycidylether %U %X %0 conference lecture %@ %A Wischke, C., Lendlein, A. %D 2011 %J Multifunktionelle polymere Hilfsstoffe, Jahrestagung der Deutschen Pharmazeutischen Gesellschaft und der Oesterreichischen Pharmazeutischen Gesellschaft 2011 %T Degradable shape-memory polymer networks as drug carriers %U %X %0 conference lecture %@ %A Wischke, C., Lendlein, A. %D 2011 %J MRS Fall 2011 Meeting %T Degradable shape-memory polymer networks as drug carriers %U %X %0 book part %@ %A Wischke, C., Neffe, A., Lendlein, A. %D 2010 %J Advances in Polymer Science - Shape-memory Polymers %P 177-206 %R doi:10.1007/12_2009_29 %T Controlled Drug Release from Biodegradable Shape-Memory Polymers %U https://doi.org/10.1007/12_2009_29 %X of drugs. This chapter provides a detailed description of the molecular basis for such multifunctional SMPs including the selection of building blocks, the polymer morphology, and the three dimensional architecture. Moreover, drug loading and release, drug effects on thermomechanical properties of SMPs, and drug release patterns in a physiological environment are described and potential applications in minimally-invasive surgery are discussed. %0 journal article %@ 0724-8741 %A Wischke, C., Lendlein, A. %D 2010 %J Pharmaceutical Research %N 4 %P 527-529 %R doi:10.1007/s11095-010-0062-5 %T Shape-Memory Polymers as Drug Carriers—A Multifunctional System %U https://doi.org/10.1007/s11095-010-0062-5 4 %X No abstract %0 conference lecture %@ %A Zhang, Y., Wischke, C., Mittal, S., Mitra, A., Schwendeman, S.P. %D 2010 %J 37th Annual Meeting & Exposition of the Controlled Release Society 2010 %T Design of controlled release PLGA microspheres for hydrophobic fenretinide %U %X %0 conference poster %@ %A Wischke, C., Weigel, J., Neffe, A.T., Lendlein, A. %D 2010 %J Biodegradable Polymers as Biomaterials, 459th WE-Heraeus-Seminar %T Understanding instability and rupture of polyalkyl 2-cyanoacrylate capsules %U %X %0 conference poster %@ %A Wischke, C., Neffe, A.T., Lendlein, A. %D 2010 %J GDCh Biannual Meeting of the GDCh-Division Macromolecular Chemistry and Polydays %T Copolyesterdimethacrylate-derived Networks combine Shape-memory, Biodegradability, and Controlled Drug Release %U %X %0 conference lecture %@ %A Wischke, C., Neffe, A.T., Lendlein, A. %D 2010 %J Biodegradable Polymers as Biomaterials, 459th WE-Heraeus-Seminar %T Multifunctional polymers combining shape-memory, drug release, and biodegradability %U %X %0 journal article %@ 0928-0987 %A Wischke, C., Neffe, A.T., Steuer, S., Lendlein, A. %D 2010 %J European Journal of Pharmaceutical Sciences %N 11 %P 136-147 %R doi:10.1016/j.ejps.2010.06.003 %T Comparing techniques for drug loading of shape-memory polymer networks–effect on their functionalities %U https://doi.org/10.1016/j.ejps.2010.06.003 11 %X A family of oligo[(var epsilon-caprolactone)-co-glycolide]dimethacrylate (oCG-DMA) derived networks of different glycolide content as well as precursor molecular weight has been synthesized by crosslinking oCG-DMA, providing matrices of different hydrophilicity, network density, and morphology at body temperature. Such networks were loaded with a hydrophilic model drug, ethacridine lactate, either before crosslinking or afterwards by swelling in drug solution. Disadvantageous alterations of the shape-memory functionality and degradation characteristics were observed only in few loaded materials. Loading by swelling generally resulted in low payloads, which slightly increased for more hydrophilic polymer networks, and a substantial burst and fast subsequent release for all investigated materials. Loading before crosslinking gave almost no burst and higher subsequent release rates over longer periods of time. Overall, depending on the needs of a specific application, a material from this polymer family with the desired mechanical properties, shape-memory functionality, and degradation pattern can be selected and combined with drugs when considering that i) loading by swelling is best suited for applications that require high initial doses and ii) loading before crosslinking allows easy variation of payloads and low burst release for therapeutics that are non-sensitive to chemical alterations during crosslinking. %0 journal article %@ 0883-7694 %A Jung, F., Wischke, C., Lendlein, A. %D 2010 %J MRS Bulletin %N 8 %P 607-613 %T Degradable, Multifunctional Cardiovascular Implants: Challenges and Hurdles %U 8 %X Polymer-coated and polymer-based cardiovascular implants are essential constituents of modern medicine and will proceed to gain importance with the demographic changes toward a society of increasing age-related morbidity. Based on the experiences with implants such as coronary or peripheral stents, which are presently widely used in clinical medicine, several properties of the next generation of cardiovascular implants have been envisioned that could be fulfilled by multifunctional polymers. The challenge is to combine tailored mechanical properties and rapid endothelialization with controlled drug release in order to modulate environmental cells and tissue. Additionally, degradability and sensitivity to external stimuli are useful in several applications. A critical function in terms of clinical complications is the hemocompatibility. The design of devices with improved hemocompatibility requires advanced in vitro test setups as discussed in depth in this article. Finally, degradable, multifunctional shape-memory polymers are introduced as a promising family of functional polymers that fulfill several requirements of modern implants and are of high relevance for cardiovascular application (e.g., stent technology). Such multifunctional polymers are a technology platform for future cardiovascular implants enabling induced autoregeneration in regenerative therapies. %0 journal article %@ 1616-5187 %A Wischke, C., Neffe, A.T., Steuer, S., Engelhardt, E., Lendlein, A. %D 2010 %J Macromolecular Bioscience %N 9 %P 1063-1072 %R doi:10.1002/mabi.201000089 %T AB-polymer Networks with Cooligoester and Poly(Eta-butyl acrylate) Segments as a Multifunctional Matrix for Controlled Drug Release %U https://doi.org/10.1002/mabi.201000089 9 %X Semi-crystalline AB-copolymer networks from oligo[(ε-caprolactone)-co-glycolide]dimethacrylates and n-butylacrylate have recently been shown to exhibit a shape-memory functionality, which may be used for self-deploying and anchoring of implants. In this study, a family of such materials differing in their molar glycolide contents χG was investigated to determine structure–property functional relationships of unloaded and drug loaded specimens. Drug loading and release were evaluated, as well as their degradation behavior in vitro and in vivo. Higher χG resulted in higher loading levels by swelling and a faster release of ethacridine lactate, lower melting temperature of polymer crystallites, and a decrease in shape fixity ratio of the programmed temporary shape. For unloaded networks, the material behavior in vivo was independent of the mechanical load associated with different implantation sites and agreed well with data from in vitro degradation studies. Thus, AB networks could be used as novel matrices for biofunctional implants, e.g., for urogenital applications, which can self-anchor in vivo and provide mechanical support, release drugs, and finally degrade in the body to excretable fragments. %0 journal article %@ 0724-8741 %A Wischke, C., Zhang, Y., Mittal, S., Schwendeman, S.P. %D 2010 %J Pharmaceutical Research %N 10 %P 2063-2074 %R doi:10.1007/s11095-010-0202-y %T Development of PLGA-Based Injectable Delivery Systems For Hydrophobic Fenretinide %U https://doi.org/10.1007/s11095-010-0202-y 10 %X Injectable carriers for fenretinide were successfully prepared, exhibiting excellent drug stability. Based on the in vitro release properties of the different carriers, the preferred injection sites and in vivo release rates will be determined in future preclinical studies. %0 conference lecture %@ %A Wischke, C., Krueger, A., Roch, T., Pierce, B.F., Li, W., Jung, F., Lendlein, A. %D 2010 %J 8th International Conference and Workshop on Biological Barriers - In vitro Tools in Nanotoxicology and Nanomedicine %T Endothelial cell response to (co)polymer nanoparticles depending on the inflammatory environment and comonomer ratio %U %X %0 journal article %@ 1743-4440 %A Lendlein, A., Behl, M., Hiebl, B., Wischke, C. %D 2010 %J Expert Review of Medical Devices %N 3 %P 357-379 %R doi:10.1586/ERD.10.8 %T Shape-memory polymers as a technology platform for biomedical applications %U https://doi.org/10.1586/ERD.10.8 3 %X Polymeric materials are clinically required for medical devices, as well as controlled drug delivery systems. Depending on the application, the polymer has to provide suitable functionalities, for example, mechanical functions or the capability to actively move, so that an implant can be inserted in a compact shape through key-hole incisions and unfold to its functional shape in the body. Shape-memory polymers, as described herein regarding their general principle, compositions and architectures, have developed to a technology platform that allows the tailored design of such multifunctionality. In this way, defined movements of implants triggered either directly or indirectly, tailored mechanical properties, capability for sterilization, biodegradability, biocompatibility and controlled drug release can be realized. This comprehensive review of the scientific and patent literature illustrates that this technology enables the development of novel medical devices that will be clinically evaluated in the near future. %0 journal article %@ 0168-3659 %A Wischke, C., Neffe, A., Steuer, S., Lendlein, A. %D 2009 %J Journal of Controlled Release %N 3 %P 243-250 %R doi:10.1016/j.jconrel.2009.05.027 %T Evaluation of a degradable shape-memory polymer network as matrix for controlleddrug release %U https://doi.org/10.1016/j.jconrel.2009.05.027 3 %X functionalities, i.e., a shape-memory effect combined with biodegradability and controlled drug release. %0 journal article %@ 0378-5173 %A Wischke, C., Zimmermann, J., Wessinger, B., Schendler, A., Borchert, H.-H., Peters, J.H., Nesselhut, T., Lorenzen, D.R. %D 2009 %J International Journal of Pharmaceutics %N 1-2 %P 61-68 %R doi:10.1016/j.ijpharm.2008.08.039 %T Poly(I:C) coated PLGA microparticles induce dendritic cell maturation %U https://doi.org/10.1016/j.ijpharm.2008.08.039 1-2 %X Microparticles from poly(d,l-lactic-co-glycolic acid) [PLGA] are of steadily rising interest for the delivery of antigens to immune cells and the induction of a long-lasting immune response for vaccination or immunological tumor therapy. However, if the desired vaccine contains only weak antigens and fails to activate the antigen presenting cells (APC), the opposite effect, i.e., the induction of immunotolerance may be observed. Therefore, it was the aim of this study to show the ability of protein loaded PLGA microparticles to additionally carry a specific, surface-coated maturation signal to human dendritic cells (DC), i.e., the most potent APC. Polyinosine-polycytidylic acid [poly(I:C)], a ligand of Toll-like receptor (TLR) 3, was efficiently bound either in a single layer or a multilayer attempt to the surface of diethylaminoethyl dextran modified PLGA microparticles. These particles were effectively phagocytized by DC ex vivo and induced a maturation similar to that achieved with a cytokine cocktail or higher concentrations of soluble poly(I:C). In conclusion, the concept of surface coating of biodegradable microparticles with selected TLR ligands might successfully be used in DC-based cell therapies for cancer or in vaccination trials to induce DC maturation and specifically amplify the immunological response to encapsulated antigens. %0 conference lecture %@ %A Wischke, C., Neffe, A., Steuer, S., Lendlein, A. %D 2009 %J 36th Annual Meeting and Exposition of the Controlled Release Society %T Amorphous Polymer Network combining Three Functionalities – Shape-memory, Biodegradability, and Drug Release %U %X %0 conference poster %@ %A Wischke, C., Neffe, A., Steuer, S., Lendlein, A. %D 2009 %J Controlled Release Society Annual Meeting & Exposition 2009 %T Amorphous polymer networks combining three functionalities – Shape-memory, biodegradability, and drug release %U %X %0 conference lecture %@ %A Wischke, C., Neffe, A., Steuer, S., Lendlein, A. %D 2009 %J MRS Spring Meeting 2009 %T Amorphous Polymer Networks Combining Three Functionalities - Shape-Memory, Biodegradability, and Drug Release %U %X %0 conference paper %@ %A Wischke, C., Neffe, A., Steuer, S., Lendlein, A. %D 2009 %J Active Polymers - MRS Symposium Proceedings, MRS Spring Meeting 2009 %P NN11-34 %R doi:10.1557/PROC-1190-NN11-34 %T Amorphous Polymer Networks Combining Three Functionalities - Shape-Memory, Biodegradability, and Drug Release %U https://doi.org/10.1557/PROC-1190-NN11-34 %X %0 conference poster %@ %A Neffe, A.T., Hanh, B.D., Steuer, S., Wischke, C., Lendlein, A. %D 2009 %J MRS Spring Meeting 2009 %T Thermomechanical Properties and Shape-Memory Capability of Drug Loaded Semi-Crystalline Polyestermethacrylate Networks %U %X %0 conference paper %@ %A Neffe, A.T., Hanh, B.D., Steuer, S., Wischke, C., Lendlein, A. %D 2009 %J Active Polymers - MRS Symposium Proceedings, MRS Spring Meeting 2009 %P NN06-02 %R doi:10.1557/PROC-1190-NN06-02 %T Thermomechanical Properties and Shape-Memory Capability of Drug Loaded Semi-Crystalline Polyestermethacrylate Networks %U https://doi.org/10.1557/PROC-1190-NN06-02 %X %0 conference poster %@ %A Schendler, A., Wessinger, B., Wischke, C., Borchert, H.-H. %D 2008 %J Der wissenschaftliche Nachwuchs stellt sich vor, Deutsche Pharmazeutische Gesellschaft %T Beschichtung von Poly(D,L-lactid-co-glycolid)-Mikropartikeln mit doppelsträngiger RNA %U %X %0 journal article %@ 0378-5173 %A Wischke, C., Schwendeman, S.P. %D 2008 %J International Journal of Pharmaceutics %N 2 %P 298-327 %R doi:10.1016/j.ijpharm.2008.04.042 %T Principles of encapsulating hydrophobic drugs in PLA/PLGA microparticles %U https://doi.org/10.1016/j.ijpharm.2008.04.042 2 %X Injectable biodegradable and biocompatible copolymers of lactic and glycolic acid (PLGA) are an important advanced delivery system for week-to-month controlled release of hydrophobic drugs (e.g., from biopharmaceutical classification system class IV), which often display poor oral bioavailability. The basic principles and considerations to develop such microparticle formulations is reviewed here based on a comprehensive study of papers and patents from the beginnings of hydrophobic drug encapsulation in polylactic acid and PLGA up through the very recent literature. Challenges with the diversity of drug properties, microencapsulation methods, and organic solvents are evaluated in light of the precedence of commercialized formulations and with a focus on decreasing the time to lab-scale encapsulation of water-insoluble drug candidates in the early stage of drug development. The influence of key formulation variables on final microparticle characteristics, and how best to avoid undesired microparticle properties, is analyzed mechanistically. Finally, concepts are developed to manage the common issues of maintaining sink conditions for in vitro drug release assays of hydrophobic compounds. Overall, against the backdrop of an increasing number of new, poorly orally available drug entities entering development, microparticle delivery systems may be a viable strategy to rescue an otherwise undeliverable substance. %0 conference lecture %@ %A Wischke, C., Neffe, A., Steuer, S., Lendlein, A. %D 2007 %J 6th International Nanomedicine and Drug Delivery Symposium, Nano DDS 2008 %T Evaluation of a degradable shape-memory polymer network as matrix for controlleddrug release %U %X functionalities, i.e., a shape-memory effect combined with biodegradability and controlled drug relea