TY - JOUR A1 - Shan, Junwen A1 - Böck, Thomas A1 - Keller, Thorsten A1 - Forster, Leonard A1 - Blunk, Torsten A1 - Groll, Jürgen A1 - Teßmar, Jörg T1 - TEMPO/TCC as a Chemo Selective Alternative for the Oxidation of Hyaluronic Acid JF - Molecules N2 - Hyaluronic acid (HA)-based hydrogels are very commonly applied as cell carriers for different approaches in regenerative medicine. HA itself is a well-studied biomolecule that originates from the physiological extracellular matrix (ECM) of mammalians and, due to its acidic polysaccharide structure, offers many different possibilities for suitable chemical modifications which are necessary to control, for example, network formation. Most of these chemical modifications are performed using the free acid function of the polymer and, additionally, lead to an undesirable breakdown of the biopolymer’s backbone. An alternative modification of the vicinal diol of the glucuronic acid is oxidation with sodium periodate to generate dialdehydes via a ring opening mechanism that can subsequently be further modified or crosslinked via Schiff base chemistry. Since this oxidation causes a structural destruction of the polysaccharide backbone, it was our intention to study a novel synthesis protocol frequently applied to selectively oxidize the C6 hydroxyl group of saccharides. On the basis of this TEMPO/TCC oxidation, we studied an alternative hydrogel platform based on oxidized HA crosslinked using adipic acid dihydrazide as the crosslinker. KW - hyaluronic acid KW - oxidation KW - hydrogel formation KW - Schiff base chemistry Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-248362 SN - 1420-3049 VL - 26 IS - 19 ER - TY - THES A1 - Shan, Junwen T1 - Tailoring Hyaluronic Acid and Gelatin for Bioprinting T1 - Modifikation von Hyaluronsäure und Gelatine für die Anwendung im Biodruck N2 - In the field of biofabrication, biopolymer-based hydrogels are often used as bulk materials with defined structures or as bioinks. Despite their excellent biocompatibility, biopolymers need chemical modification to fulfill mechanical stability. In this thesis, the primary alcohol of hyaluronic acid was oxidized using TEMPO/TCC oxidation to generate aldehyde groups without ring-opening mechanism of glycol cleavage using sodium periodate. For crosslinking reaction of the aldehyde groups, adipic acid dihydrazide was used as bivalent crosslinker for Schiff Base chemistry. This hydrogel system with fast and reversible crosslinking mechanism was used successfully as bulk hydrogel for chondrogenic differentiation with human mesenchymal stem cells (hMSC). Gelatin was modified with pentenoic acid for crosslinking reaction via light controllable thiol-ene reaction, using thiolated 4-arm sPEG as multivalent crosslinker. Due to preservation of the thermo responsive property of gelatin by avoiding chain degradation during modification reaction, this gelatin-based hydrogel system was successfully processed via 3D printing with low polymer concentration. Good cell viability was achieved using hMSC in various concentrations after 3D bioprinting and chondrogenic differentiation showed promising results. N2 - Im Bereich der Biofabrikation werden Hydrogele auf Biopolymerbasis häufig als Bulkmaterial mit definierten Strukturen oder als Biotinten verwendet. Obwohl Biopolymere eine hervorragende Biokompatibilität aufweisen, müssen sie jedoch chemisch modifiziert werden, um gewisse mechanische Stabilität für den Einsatz in der Biofabrikation zu erreichen. In dieser Arbeit wurde der primäre Alkohol der Hyaluronsäure mit Hilfe der TEMPO/TCC-Oxidation oxidiert, um Aldehydgruppen zu generieren. Dabei findet kein Ringöffnungsmechanismus statt, wie er bei der Glykolspaltung mit Natriumperiodat vorkommt. Für die Vernetzungsreaktion der Aldehydgruppen wurde Adipinsäuredihydrazid als bivalenter Vernetzer für die Bildung der Schiffschen Base verwendet. Dieses Hydrogelsystem mit schnellem und reversiblem Vernetzungsmechanismus wurde erfolgreich als Bulkhydrogel für die chondrogene Differenzierung mit humanen mesenchymalen Stammzellen (hMSC) erfolgreich eingesetzt. Als Mikrogele könnte das System in künftigen Forschungsarbeiten auf seine Verdruckbarkeit getestet werden. Gelatine wurde mit Pentensäure modifiziert, um die Vernetzungsreaktion über eine lichtkontrollierbare Thiol-En-Reaktion durchzuführen, bei der thioliertes 4-armiges sPEG als multivalenter Vernetzer verwendet wurde. Da die thermoresponsive Eigenschaft der Gelatine erhalten blieb, indem der Kettenabbau während der Modifizierungsreaktion vermieden wurde, konnte dieses Hydrogelsystem auf Gelatinebasis erfolgreich im 3D-Druck mit niedriger Polymerkonzentration verarbeitet werden. Mit hMSC in verschiedenen Konzentrationen wurde nach dem 3D-Biodruck eine gute Zellviabilität erreicht und die chondrogene Differenzierung zeigte vielversprechende Ergebnisse. KW - Hydrogel KW - Biomaterial KW - Biofabrication of hydrogels KW - Biomaterial KW - Chemical modification of biopolymers KW - Chondrogenic differentiation Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-298256 ER - TY - JOUR A1 - Blum, Carina A1 - Taskin, Mehmet Berat A1 - Shan, Junwen A1 - Schilling, Tatjana A1 - Schlegelmilch, Katrin A1 - Teßmar, Jörg A1 - Groll, Jürgen T1 - Appreciating the First Line of the Human Innate Immune Defense: A Strategy to Model and Alleviate the Neutrophil Elastase-Mediated Attack toward Bioactivated Biomaterials JF - Small N2 - Biointerface engineering is a wide-spread strategy to improve the healing process and subsequent tissue integration of biomaterials. Especially the integration of specific peptides is one promising strategy to promote the regenerative capacity of implants and 3D scaffolds. In vivo, these tailored interfaces are, however, first confronted with the innate immune response. Neutrophils are cells with pronounced proteolytic potential and the first recruited immune cells at the implant site; nonetheless, they have so far been underappreciated in the design of biomaterial interfaces. Herein, an in vitro approach is introduced to model and analyze the neutrophil interaction with bioactivated materials at the example of nano-bioinspired electrospun surfaces that reveals the vulnerability of a given biointerface design to the contact with neutrophils. A sacrificial, transient hydrogel coating that demonstrates optimal protection for peptide-modified surfaces and thus alleviates the immediate cleavage by neutrophil elastase is further introduced. KW - solution electrospinning KW - human neutrophil elastase (HNE) KW - peptide immobilization KW - polymeric matrix Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-257691 VL - 17 IS - 13 ER - TY - JOUR A1 - Weis, Matthias A1 - Shan, Junwen A1 - Kuhlmann, Matthias A1 - Jungst, Tomasz A1 - Tessmar, Jörg A1 - Groll, Jürgen T1 - Evaluation of hydrogels based on oxidized hyaluronic acid for bioprinting JF - Gels N2 - In this study, we evaluate hydrogels based on oxidized hyaluronic acid, cross-linked with adipic acid dihydrazide, for their suitability as bioinks for 3D bioprinting. Aldehyde containing hyaluronic acid (AHA) is synthesized and cross-linked via Schiff Base chemistry with bifunctional adipic acid dihydrazide (ADH) to form a mechanically stable hydrogel with good printability. Mechanical and rheological properties of the printed and casted hydrogels are tunable depending on the concentrations of AHA and ADH cross-linkers. KW - biofabrication KW - bioprinting KW - hyaluronic acid Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197600 SN - 2310-2861 VL - 4 IS - 4 ER -