Bioactive and Injectable Granular Hydrogels Incorporating Decellularized Extracellular Matrix

Decellularized extracellular matrices (dECMs) provide bioactive cues that may be useful for the repair of fibrocartilaginous tissues, such as the temporomandibular joint disc (TMJd), which lacks a natural regenerative capacity. While potent in bioactivity, dECM hydrogels do not possess the mechanical properties necessary for joint repair, motivating the development of improved materials. Granular hydrogels provide a unique opportunity to repair tissues by mechanically stabilizing the defect with injectable, jammed hydrogel microparticles that exhibit microporosity to support cellular infiltration. Here, we combined the bioactivity of dECM with the stability of norbornene hyaluronic acid (NorHA) granular hydrogels to create a system that promotes cell adhesion and allows for ECM release. Two concentrations of dECM (0.4% and 0.8%, w/v, dry weight) were encapsulated within NorHA microgels and shown to increase microgel stiffness and support ECM release over time. The microgels were formed into granular hydrogels with shear-thinning and self-healing properties that also undergo secondary cross-linking either with photo-cross-linking via visible light or with the addition of an interstitial dECM. The incorporated dECM supported the adhesion of fibrochondrocytes. The addition of dECM to microgels and within the interstitial space resulted in an injectable and bioactive biomaterial.