Porcine Vocal Fold Lamina Propria-Derived Biomaterials Modulate TGF-β1-Mediated Fibroblast Activation in Vitro

The vocal fold lamina propria (VFLP), one of the outermost layers of the vocal fold (VF), is composed of tissue-specific extracellular matrix (ECM) proteins and is highly susceptible to injury. Various biomaterials have been clinically tested to treat voice disorders (e.g., hydrogels, fat, and hyaluronic acid), but satisfactory recovery of the VF functionality remains elusive. Fibrosis or scar formation in the VF is a major challenge, and the development and refinement of novel therapeutics that promote the healing and normal function of the VF are needed. Injectable hydrogels derived from native tissues have been previously reported with major advantages over synthetic hydrogels, including constructive tissue remodeling and reduced scar tissue formation. This study aims to characterize the composition of a decellularized porcine VFLP-ECM scaffold and the cytocompatibility and potential antifibrotic properties of a hydrogel derived from VFLP-ECM. In addition, we isolated potential matrix-bound vesicles (MBVs) and macromolecules from the VFLP-ECM that also downregulated smooth muscle actin ACTA2 under transforming growth factor-beta 1 (TGF-β1) stimulation. The results provide evidence of the unique protein composition of the VFLP-ECM and the potential link between the components of the VFLP-ECM and the inhibition of TGF-β1 signaling observed in vitro when transformed into injectable forms.