Enzyme-mediated tissue adhesive hydrogels for meniscus repair

Abstract

Meniscus tissues have limited regenerative capacity once damaged. The treatment options for the meniscus tissue regeneration have been limited to arthroscopic meniscectomy or surgical interventions. The injectable hydrogels based system would provide an alternative to the conventional meniscus therapy by providing a minimally invasive treatment alternative. Here we utilized enzyme-based approaches to fabricate tissue adhesive hydrogels for meniscus repair. Tyramine (TA) conjugated hyaluronic acid (TA-HA) and gelatin are susceptible to tyrosinase (TYR)-mediated crosslinking in vitro and in vivo. Importantly, mechanical properties and degradation kinetics are modulated by the TA substitution and TYR concentrations. In addition, TYR -mediated crosslinking displayed tissue-adhesive properties. Furthermore, fibrochondrocyte-laden and TYR-crosslinked hydrogels demonstrated strong biocompatibility and resulted in enhancement of cartilage-specific gene expression and matrix synthesis. Overall, this represents a potential application of enzyme-mediated crosslinking hydrogels for meniscus tissue engineering.

Keywords: HA; Injectable hydrogel; Meniscus regeneration; Tyrosinase.