Clicktetrazine dECM-alginate hydrogels for injectable, mechanically mimetic, and biologically active vocal fold biomaterials.

Current injectable biomaterials for vocal fold disorders suffer from fast degradation and require frequent re-injection. Decellularized extracellular matrix (dECM) hydrogels are a tissue-derived, injectable biomaterial with intrinsic regenerative capacity. However, dECM hydrogels often exhibit mechanical instability and share the same problems with degradation as existing vocal fold biomaterials. In this work, we developed a composite dECM-alginate hydrogel with bioorthogonal click tetrazine ligation with improved stability, biocompatibility and regenerative capacity. dECM was extracted from two sources: tissue-specific vocal fold mucosa and scalable small intestinal submucosa for comparative analysis. Click dECM hydrogels from both sources were tunable and matched mechanical properties of native human vocal folds. The click dECM hydrogels showed capacity to resist contraction and modulate bioactive molecule secretion by fibroblasts, as well as stimulate the initial endothelial cell elongation phase of vasculogenesis. When injected subcutaneously into rats, both gels exhibit a strong initial immune response, followed by integration with the surrounding tissue by day 21. Overall, our click dECM hydrogels showed improved stability over previous dECM hydrogels and their performance was independent of tissue source.