Extracellular-Matrix-Based Materials from Decellularized Tissue: Opportunities, Challenges, and Future Directions in Regenerative Medicine.

Extracellular matrix (ECM) biomaterials have been used as inductive scaffolds to promote tissue regeneration in a variety of clinical applications. ECM biomaterials derived from decellularized tissue (dECM)   can retain essential bioactive components of the native ECM that can guide cellular processes; however, the composition and bioactivity of the dECM is highly dependent on the decellularization and postprocessing methods. This intrinsic regenerative potential underpins the clinical success of dECM biomaterials in applications including soft tissue repair, cardiac reconstruction, and urological interventions. Here, clinical use of current dECM biomaterials, advances in the fabrication of dECM biomaterials, and hurdles to clinical translation of dECM products are discussed. Clinical use to date has mostly been limited to native dECM sheets or milling to generate powder dECM. Recent advances in fabrication methods from electrospinning to 3D printing have expanded the potential clinical applications of dECM biomaterials by increasing the structural and compositional complexity available to researchers. Despite significant progress, challenges remain in standardizing decellularization processes, optimizing dECM bioactivity retention, and ensuring mechanical compatibility with native tissues. Future research should focus on refining fabrication techniques and establishing standardized criteria for dECM characterization and translational pathways.