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)的诱人细胞载体，但缺乏足够的机械稳定性来实现成功的骨再生。因此，该项目旨在开发一种细胞兼容、可生物降解的注射系统，注射后快速凝胶化，并在数小时至数天内进一步固化。具有调节亲水性-亲油性平衡的官能化大分子将被开发为凝胶形成大分子。这些大分子单体将包含不同的官能团，允许物理凝胶化和独立的化学交联步骤。通过这种方式，开发的大分子单体可以通过两种机械和动力学独立的方式进行交联。注射后，温度的升高将刺激初始的、快速的凝胶机制。为了固化系统，触发第二胶凝机制的生物相容物质将从合并的输送装置中缓慢释放。后者将被设计为溶解，在硬化的基质中创建一个孔隙网络。通过包裹来自骨髓的细胞(MSCs)，将创造出可注射的自硬化骨替代品，并在体外和体内进行测试。在一种无细胞的方法中，通过用加载了骨诱导生长因子和血管生成因子的自硬化基质填充骨缺损来诱导新生组织的形成。所提出的可注射和承载细胞载体将极大地改进TE方法以再生颅颌面部骨缺损。

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.