Apoptosis as a Strategy for Enhancing Decellularization and Remodeling of Tissue-Engineered Heart Valves

This study introduces a novel apoptosis-assisted decellularization strategy for human tissue-engineered matrices (hTEMs) and tissue-engineered heart valves (TEHVs) that minimizes immunogenic damage-associated molecular patterns (DAMPs) while preserving extracellular matrix (ECM) integrity. Human dermal fibroblasts (hDFBs) were genetically modified with an inducible caspase 9 (iCasp9) system to trigger apoptosis prior to detergent treatment, achieving more complete cell clearance and reduced intracellular protein residue. The resulting hTEMs and TEHVs maintained ECM architecture and mechanical properties while exhibiting enhanced host remodeling potential. Functionalization with the apoptotic secretome (APOSEC) further promoted endothelialization and macrophage-mediated tissue repair, advancing the clinical translation of bioengineered valves.