Abstract / Summary
Conventional biomaterials for tissue regeneration often provide inadequate vascular support, mechanical compatibility, and control over cell differentiation, limiting their ability to reproduce the biochemical complexity and mechanical heterogeneity of native extracellular matrix (ECM). These shortcomings can impair cell-matrix interactions, provoke foreign body reactions, and compromise healing. Decellularized extracellular matrix (dECM) retains key bioactive components and native three-dimensional architecture that regulate cell behavior and support tissue regeneration. However, insufficient mechanical strength, limited shape adaptability, and inadequate control over biological signaling constrain its application in complex defects. Functional design and processing are therefore essential to preserve tissue-specific biological properties while enabling mechanical adaptation, structural guidance, vascularization, and local microenvironmental regulation. This review summarizes the preparation methods and evaluation criteria of dECM, and native dECM scaffold implantation, injectable hydrogels, electrospun fibers, and multi-dimensional bio-ink printing, centered on its functionalized morphologies and processing techniques, are emphatically proposed as the four core design strategies. Each strategy is further elaborated to be customized to address common reparative challenges, including insufficient vascularization, poor mechanical adaptation, and lack of structure guidance, thereby maximizing the biological efficacy of dECM. Finally, this review outlines the critical challenges and transformation opportunity for dECM in clinical applications, aiming to guide the rational design and functional assessment needed for its precise tissue engineering use.