Entwicklung eines injizierbaren, selbsthärtenden Zellträgers für die Züchtung von mineralisiertem Gewebe, insbesondere zur zellbasierten Regeneration von Defekten des Schädel- und Kieferknochens

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Injectable hydrogel systems have become attractive cell carriers for orthopedic tissue engineering (TE) but lack of sufficient mechanical stability for a successful bone regeneration. Consequently, this project aims at developing a cytocompatible, biodegradable injectable system, which gels quickly after injection and further solidifies over hours to days. Dunctional cacromolecules with adjusted hydrophilic-lipophilic balances will be developed as gel-forming macromers. These macromers will contain different functional groups that allow for a physical gelation and an independent chemical crosslinking step. This way, the developed macromers can be crosslinked in two mechanistically and kinetically independent ways. After injection, the temperature increase will stimulate the initial, fast gelation mechanism. To solidify the systems, biocompatible substances that trigger the second gelation mechanism will be slowly released from incorporated delivery devices. The latter will be desingned to dissolve, creating a network of pores within the hardened matrix. By encapsulating cells from the bone marrow (MSCs), injectable self-hardening bone substitutes will be created and tested in vitro and in vivo. In a cell-free approach, de novo formation will be induced by filling bone defects with the self-hardening matrix loaded with osteoinductive and angiogenic growth factors. The proposed injectable and load-bearing cell carriers will greatly improve the TE approach to regenerate cranio- and maxillofacial bone defects.