Unraveling the Relevance of Tissue-Specific Decellularized Extracellular Matrix Hydrogels for Vocal Fold Regenerative Biomaterials: A Comprehensive Proteomic and In Vitro Study

Decellularized extracellular matrix (dECM) is a promising material for tissue engineering applications. Tissue-specific dECM is seen as a favorable material that recapitulates a native-like microenvironment for cellular remodeling. However, the minute quantity of dECM derivable from small organs like the vocal fold (VF) hampers manufacturing scalability. Small intestinal submucosa (SIS), a commercial product with proven regenerative capacity, may be a viable option for VF applications. This study aims to compare SIS and VF dECM hydrogels with respect to protein content and functionality using mass spectrometry-based proteomics and in vitro studies. Proteomic analysis reveals that VF and SIS dECM share 75% of core matrisome proteins. Although VF dECM proteins have greater overlap with native VF, SIS dECM shows less cross-sample variability. Following decellularization, significant reductions of soluble collagen (61%), elastin (81%), and hyaluronan (44%) are noted in VF dECM. SIS dECM contains comparable elastin and hyaluronan but 67% greater soluble collagen than VF dECM. Cells deposit more neo-collagen on SIS than VF-dECM hydrogels, but comparable neo-elastin (approximate to 50 mu g scaffold(-1)) and neo-hyaluronan (approximate to 6 mu g scaffold(-1)). Overall, SIS dECM possesses a reasonably similar proteomic profile and regenerative capacity to VF dECM. SIS dECM is a promising alternative for dECM-derived biomaterials for VF regeneration.