Decellularized Cell‐Secreted Extracellular Matrices as Biomaterials for Tissue Engineering

The extracellular matrix (ECM) is the naturally secreted biomaterial scaffold that provides support and regulates key aspects of cell behavior. This dynamic and complex network of structural proteins, proteoglycans, and soluble cues defines the cell microenvironment and is essential for tissue homeostasis. Because tissue engineering approaches aim to recapitulate aspects of the microenvironment to instruct tissue regeneration, ECM-inspired or -derived scaffolds are some of the earliest tissue-engineered constructs reported. However, conventional single-protein constructs fail to provide the biochemical and structural complexity of the native ECM. Decellularized ECM is under investigation to improve cell adhesion, cell remodeling, migration, proliferation, and differentiation within tissue-engineered constructs. However, challenges associated with poor mechanical properties and inherent chemical instability compared to synthetic or other natural polymers require additional considerations. This review describes the bioactive properties of ECM, current strategies to efficiently decellularize cell-secreted and tissue-derived ECM, standard fabrication techniques for ECM constructs, and current developments in the field of ECM-based musculoskeletal platforms.