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

可注射水凝胶系统已成为骨科组织工程（TE）中有吸引力的细胞载体，但缺乏足够的机械稳定性来成功地进行骨再生。因此，该项目旨在开发一种细胞相容、可生物降解的可注射系统，该系统在注射后迅速凝胶化，并在数小时至数天内进一步固化。具有调节的亲水-亲脂平衡的功能大分子将被开发为成胶大分子。这些大分子将包含不同的官能团，允许物理凝胶和独立的化学交联步骤。这样，开发的大分子就可以以两种机械和动力学独立的方式交联。注射后，温度升高会刺激初始的、快速的凝胶机制。为了固化系统，触发第二凝胶机制的生物相容性物质将从合并的输送装置中缓慢释放。后者将被设计成溶解，在硬化的基体中形成一个孔隙网络。通过封装骨髓细胞（MSCs），可注射的自硬化骨替代品将被创造出来，并在体外和体内进行测试。在无细胞的方法中，将用装载骨诱导和血管生成生长因子的自硬化基质填充骨缺损来诱导新生形成。所提出的可注射和承载细胞载体将极大地改善TE方法再生颅颌面骨缺损。

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.