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

开发可注射的自硬化细胞载体，用于培养矿化组织，特别是用于颅骨和颌骨缺陷的细胞再生

• 批准号: 5452534
• 负责人: Professor Dr. Michael Hacker
• 金额: --
• 依托单位: Institut für Pharmazeutische Technologie und Biopharmazie
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2005
• 资助国家: 德国
• 起止时间: 2004-12-31 至 2007-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5452534?language=en
• 关键词: Entwicklung; eines; injizierbaren; selbsth; rtenden

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.

可注射水凝胶系统已成为骨科组织工程（TE）有吸引力的细胞载体，但缺乏足够的机械稳定性来成功进行骨再生。因此，该项目旨在开发一种细胞相容性、可生物降解的注射系统，该系统在注射后迅速凝胶化，并在数小时至数天内进一步凝固。具有调整亲水亲油平衡的功能大分子将被开发为凝胶形成大分子单体。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。这样，所开发的大分子单体可以以两种机械和动力学独立的方式交联。注射后，温度升高将刺激初始的快速凝胶机制。为了固化系统，触发第二凝胶化机制的生物相容性物质将从所结合的输送装置中缓慢释放。后者将被设计为溶解，在硬化基质内形成孔隙网络。通过封装来自骨髓（MSC）的细胞，将创建可注射的自硬化骨替代物并进行体外和体内测试。在无细胞方法中，通过用负载有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从头形成。所提出的可注射和承重细胞载体将极大地改进颅颌面骨缺损再生的 TE 方法。