Extensible Collagen Hydrogels for Cartilage Tissue Engineering

本研究旨在开发具有与之相匹配的延展性和韧性的组织工程耳廓软骨

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.