From biological scaffold to multifunctional bioplatform: research progress and applications of decellularized extracellular matrix

Abstract

Decellularized extracellular matrix (dECM) is a biomaterial generated by the selective removal of cellular components from native tissues while preserving the three-dimensional ultrastructure and endogenous biochemical cues of the extracellular matrix. Owing to its favorable biocompatibility, low immunogenicity, and capacity to mimic tissue-specific microenvironments, dECM has been increasingly explored across a wide range of biomedical applications. Its role has expanded from a conventional scaffold for tissue repair to a multifunctional biomaterial platform integrating 3D bioprinting bioinks, organ-on-a-chip matrices, organoid culture systems, and immunomodulatory applications. This review summarizes recent advances in dECM preparation, engineering applications, and clinical translation between 2020 and 2026. In terms of preparation methodology, conventional single physical, chemical, or enzymatic decellularization strategies are being replaced by integrated and tissue-specific combinatorial approaches. Emerging techniques, including supercritical CO2 treatment, macromolecular crowding, and multi-index-guided automated processing, provide new routes for standardized and scalable dECM production. In engineering applications, dECM has achieved key breakthroughs in 3D bioprinting, organ-on-a-chip platforms, and tissue repair, marking a paradigm shift from structural support to functional regulation. In clinical translation, dECM products have demonstrated promising therapeutic potential in hard-to-heal wound repair. Finally, this review discusses the major technical and translational challenges currently facing the dECM field, including insufficient standardization of preparation protocols, potential immunogenic risks, suboptimal mechanical matching, and incomplete regulatory frameworks. Future directions, including precision whole-organ decellularization, programmable immunomodulation, and intelligent manufacturing, are further discussed to inform the continued development and clinical translation of dECM-based biomaterials.