Decellularized matrix (dECM) derived from small intestine submucosa (SIS) has been increasingly used in tissue engineering and regenerative medicine. While dECM provides cell-adhesive and protease-labile sequences to support cell-matrix interactions, its crosslinking into hydrogels has been largely limited to temperature-induced gelation, which offers limited tunability. To address this challenge, we previously reported the synthesis of bovine decellularized SIS-norbornene (dSIS-NB) for crosslinking into cytocompatible thiol-norbornene hydrogels with pro-angiogenic and pro-vasculogenic properties. In this study, we conducted proteomic profiling to analyze the protein compositions of bovine dSIS and dSIS-NB. In addition to various collagens, we discovered that bovine dSIS contained significant amounts of fibrillin-I, a glycoprotein stabilized by intra- and inter-molecular disulfide bonds. We leveraged these disulfide bonds to fabricate 'self-clickable' dSIS-NB thiol-norbornene hydrogels without the need for additional thiol-bearing crosslinker (e.g., 4-arm poly(ethylene glycol)-thiol). Furthermore, we exploited thiol-disulfide exchange in self-clickable dSIS-NB hydrogels to enable light-induced spatiotemporal tuning of hydrogel stiffness and labeling of bioactive ligands. Finally, the dynamic and self-clickable dSIS-NB hydrogels were used as an in vitro cell culture model to study local vascular compression and as an injectable, cell-laden matrix to treat volumetric muscle loss.
Duong et al. (Mon,) studied this question.