Extensible Collagen Hydrogels for Cartilage Tissue Engineering

本研究旨在开发具有与之相匹配的延伸性和韧性的组织工程耳软骨。 由天然组织制成。小耳等先天畸形致儿童耳廓畸形 临床负担，伴随着显著的心理疾病和合理的偏侧困难。 自体软骨移植是目前的临床护理标准，不能用于耳廓移植。 对于5岁以下儿童，由于供体软骨不足而进行重建。组织工程耳廓 成形术是一种可行的新软骨形成策略，可用于不能满足当前需要的儿童。 护理标准。然而，用于组织工程的耳软骨材料还不能 实现本机级别的可扩展性和韧性。天然材料，如贻贝丝线，可以实现 通过形成多组氨酸和多巴金属络合物，具有高延展性和韧性。这些复合体 提高许多水凝胶体系的延展性和韧性。然而，这种复杂的形成并没有 成功应用于胶原蛋白水凝胶体系。作者的初步工作表明，藻酸盐 低聚物可以在不破坏胶原结构或功能的情况下连接到胶原分子上，并且 导致了可扩展性的显著改进。作者们假设，改变疾病的程度 藻酸盐低聚物的偶联和这些低聚物的长度将导致在 生成的胶原蛋白凝胶。因此，目标1将确定延伸性和韧性的最佳参数， 而不会破坏原有的结构和功能。通过提高可伸缩性和韧性， 在胶原水凝胶的基础上，作者假设体外和体内培养的 耳穴结构也将同样得到改进。因此，目标2旨在制造耳廓软骨细胞种子结构，并测试由此产生的机械和生化发展。同样，目标3也是 目的：在小鼠真皮下建立耳廓软骨细胞模型，并对其结构进行分析 机械、生化和组织学的发展。这些目标结合在一起，将产生耳廓软骨。 与小耳畸形患者弹性软骨的天然机械功能相匹配的替代物 耳廓畸形。

This study aims to develop tissue engineered auricular cartilage with extensibility and toughness matching that of native tissue. Auricular malformation in children due to congenital defects such as microtia present an unmet clinical burden, with significant associated psychological morbidities and sound lateralization difficulties. Autologous cartilage grafts, which are the current clinical standard of care, cannot be used in auricular reconstruction for children under 5 years old, due to insufficient donor cartilage. Tissue engineered auricle formation is a viable strategy for neo-cartilage formation and can be implemented in children unmet by current standards of care. However, materials for tissue engineering of auricular cartilage have not been able to achieve native levels of extensibility and toughness. Natural materials such as mussel byssal threads achieve high extensibility and toughness through poly-histidine- and DOPA-metal complex formation. These complexes improve extensibility and toughness in many hydrogel systems. However, this complex formation has not been successfully applied to collagen hydrogel systems. Preliminary work by the author has shown that alginate oligomers can be conjugated to collagen molecules without disruption of collagen structure or function and leads to significant improvements in extensibility. The authors hypothesize that changing the extent of conjugation of alginate oligomers, and the length of those oligomers, will lead to changes in extensibility in resultant collagen gels. Thus, Aim 1 will determine the optimal parameters for extensibility and toughness, without disruption of native structure and function. By improving the extensibility and toughness of the underlying collagen hydrogel, the authors hypothesize that the mechanics of in vitro and in vivo cultured auricular constructs will similarly be improved. Aim 2 is thus directed at fabrication of auricular chondrocyte-seeded constructs, with testing of resultant mechanical and biochemical development. Similarly, Aim 3 is directed at fabrication of auricular chondrocytes in a murine sub-dermal model, with analysis of construct mechanical, biochemical, and histological development. Combined, these aims will result in auricular cartilage replacements that match the native mechanical function of elastic cartilage in patients with microtia and auricular deformities.