@article{HahnBeudertGutmannetal.2021,
  author    = {Hahn, Lukas and Beudert, Matthias and Gutmann, Marcus and Keßler, Larissa and Stahlhut, Philipp and Fischer, Lena and Karakaya, Emine and Lorson, Thomas and Thievessen, Ingo and Detsch, Rainer and L{\"u}hmann, Tessa and Luxenhofer, Robert},
  title     = {From Thermogelling Hydrogels toward Functional Bioinks: Controlled Modification and Cytocompatible Crosslinking},
  series = {Macromolecular Bioscience},
  volume    = {21},
  journal   = {Macromolecular Bioscience},
  number    = {10},
  doi       = {10.1002/mabi.202100122},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257542},
  year      = {2021},
  abstract  = {Hydrogels are key components in bioink formulations to ensure printability and stability in biofabrication. In this study, a well-known Diels-Alder two-step post-polymerization modification approach is introduced into thermogelling diblock copolymers, comprising poly(2-methyl-2-oxazoline) and thermoresponsive poly(2-n-propyl-2-oxazine). The diblock copolymers are partially hydrolyzed and subsequently modified by acid/amine coupling with furan and maleimide moieties. While the thermogelling and shear-thinning properties allow excellent printability, trigger-less cell-friendly Diels-Alder click-chemistry yields long-term shape-fidelity. The introduced platform enables easy incorporation of cell-binding moieties (RGD-peptide) for cellular interaction. The hydrogel is functionalized with RGD-peptides using thiol-maleimide chemistry and cell proliferation as well as morphology of fibroblasts seeded on top of the hydrogels confirm the cell adhesion facilitated by the peptides. Finally, bioink formulations are tested for biocompatibility by incorporating fibroblasts homogenously inside the polymer solution pre-printing. After the printing and crosslinking process good cytocompatibility is confirmed. The established bioink system combines a two-step approach by physical precursor gelation followed by an additional chemical stabilization, offering a broad versatility for further biomechanical adaptation or bioresponsive peptide modification.},
  language  = {en}
}
@article{LorsonRuoppNadernezhadetal.2020,
  author    = {Lorson, Thomas and Ruopp, Matthias and Nadernezhad, Ali and Eiber, Julia and Vogel, Ulrich and Jungst, Tomasz and L{\"u}hmann, Tessa},
  title     = {Sterilization Methods and Their Influence on Physicochemical Properties and Bioprinting of Alginate as a Bioink Component},
  series = {ACS Omega},
  volume    = {5},
  journal   = {ACS Omega},
  number    = {12},
  doi       = {10.1021/acsomega.9b04096},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229460},
  pages     = {6481-6486},
  year      = {2020},
  abstract  = {Bioprinting has emerged as a valuable threedimensional (3D) biomanufacturing method to fabricate complex hierarchical cell-containing constructs. Spanning from basic research to clinical translation, sterile starting materials are crucial. In this study, we present pharmacopeia compendial sterilization methods for the commonly used bioink component alginate. Autoclaving (sterilization in saturated steam) and sterile filtration followed by lyophilization as well as the pharmacopeia non-compendial method, ultraviolet (UV)-irradiation for disinfection, were assessed. The impact of the sterilization methods and their effects on physicochemical and rheological properties, bioprinting outcome, and sterilization efficiency of alginate were detailed. Only sterile filtration followed by lyophilization as the sterilization method retained alginate's physicochemical properties and bioprinting behavior while resulting in a sterile outcome. This set of methods provides a blueprint for the analysis of sterilization effects on the rheological and physicochemical pattern of bioink components and is easily adjustable for other polymers used in the field of biofabrication in the future.},
  language  = {en}
}
@article{LuebtowLorsonFingeretal.2020,
  author    = {L{\"u}btow, Michael M. and Lorson, Thomas and Finger, Tamara and Gr{\"o}ber-Becker, Florian-Kai and Luxenhofer, Robert},
  title     = {Combining Ultra-High Drug-Loaded Micelles and Injectable Hydrogel Drug Depots for Prolonged Drug Release},
  series = {Macromolecular Chemistry and Physics},
  volume    = {221},
  journal   = {Macromolecular Chemistry and Physics},
  number    = {1},
  doi       = {10.1002/macp.201900341},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-208115},
  pages     = {1900341},
  year      = {2020},
  abstract  = {Hydrogel-based drug depot formulations are of great interest for therapeutic applications. While the biological activity of such drug depots is often characterized well, the influence of incorporated drug or drug-loaded micelles on the gelation properties of the hydrogel matrix is less investigated. However, the latter is of great importance from fundamental and application points of view as it informs on the physicochemical interactions of drugs and water-swollen polymer networks and it determines injectability, depot stability, as well as drug-release kinetics. Here, the impact of incorporated drug, neat polymer micelles, and drug-loaded micelles on the viscoelastic properties of a cytocompatible hydrogel is investigated systematically. To challenge the hydrogel with regard to the desired application as injectable drug depot, curcumin (CUR) is chosen as a model compound due to its very low-water solubility and limited stability. CUR is either directly solubilized by the hydrogel or pre-incorporated into polymer micelles. Interference of CUR with the temperature-induced gelation process can be suppressed by pre-incorporation into polymer micelles forming a binary drug delivery system. Drug release from a collagen matrix is studied in a trans-well setup. Compared to direct injection of drug formulations, the hydrogel-based systems show improved and extended drug release over 10 weeks.},
  language  = {en}
}
@phdthesis{Lorson2019,
  author    = {Lorson, Thomas},
  title     = {Novel Poly(2-oxazoline) Based Bioinks},
  doi       = {10.25972/OPUS-18051},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-180514},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {Motivated by the great potential which is offered by the combination of additive manufacturing and tissue engineering, a novel polymeric bioink platform based on poly(2 oxazoline)s was developed which might help to further advance the young and upcoming field of biofabrication. In the present thesis, the synthesis as well as the characteristics of several diblock copolymers consisting of POx and POzi have been investigated with a special focus on their suitability as bioinks. In general, the copolymerization of 2-oxazolines and 2-oxazines bearing different alkyl side chains was demonstrated to yield polymers in good agreement with the degree of polymerization aimed for and moderate to low dispersities. For every diblock copolymer synthesized during the present study, a more or less pronounced dependency of the dynamic viscosity on temperature could be demonstrated. Diblock copolymers comprising a hydrophilic PMeOx block and a thermoresponsive PnPrOzi block showed temperature induced gelation above a degree of polymerization of 50 and a polymer concentration of 20 wt\%. Such a behavior has never been described before for copolymers solely consisting of poly(cyclic imino ether)s. Physically cross linked hydrogels based on POx b POzi copolymers exhibit reverse thermal gelation properties like described for solutions of PNiPAAm and Pluronic F127. However, by applying SANS, DLS, and SLS it could be demonstrated that the underlying gel formation mechanism is different for POx b POzi based hydrogels. It appears that polymersomes with low polydispersity are formed already at very low polymer concentrations of 6 mg/L. Increasing the polymer concentration resulted in the formation of a bicontinuous sponge like structure which might be formed due to the merger of several vesicles. For longer polymer chains a phase transition into a gyroid structure was postulated and corresponds well with the observed rheological data. Stable hydrogels with an unusually high mechanical strength (G' ~ 4 kPa) have been formed above TGel which could be adjusted over a range of 20 °C by changing the degree of polymerization if maintaining the symmetric polymer architecture. Variations of the chain ends revealed only a minor influence on TGel whereas the influence of the solvent should not be neglected as shown by a comparison of cell culture medium and MilliQ water. Rotationally as well as oscillatory rheological measurements revealed a high suitability for printing as POx b POzi based hydrogels exhibit strong shear thinning behavior in combination with outstanding recovery properties after high shear stress. Cell viability assays (WST-1) of PMeOx b PnPrOzi copolymers against NIH 3T3 fibroblasts and HaCat cells indicated that the polymers were well tolerated by the cells as no dose-dependent cytotoxicity could be observed after 24 h at non-gelling concentrations up to 100 g/L. In summary, copolymers consisting of POx and POzi significantly increased the accessible range of properties of POx based materials. In particular thermogelation of aqueous solutions of diblock copolymers comprising PMeOx and PnPrOzi was never described before for any copolymer consisting solely of POx or POzi. In combination with other characteristics, e.g. very good cytocompatibility at high polymer concentrations and comparably high mechanical strength, the formed hydrogels could be successfully used for 3D bioprinting. Although the results appear promising and the developed hydrogel is a serious bioink candidate, competition is tough and it remains an open question which system or systems will be used in the future.},
  subject      = {Polymere},
  language  = {en}
}