Synergistic strategies in tissue engineering: The role of exosomes and decellularized extracellular matrix hydrogels

Tissue engineering aims to mimic the natural microenvironment of biological structures by utilizing the distinctive characteristics of extracellular matrix (ECM) scaffolds. The combination of decellularized extracellular matrix hydrogels (dECMHs) with exosomes (EXs) represents an innovative therapeutic approach for tissue regeneration. These dECMHs, sourced from diverse tissues, provide biocompatible scaffolds that conform to irregular defect geometries, thereby addressing the limitations of conventional ECM scaffolds. EXs, which are nanovesicles secreted by virtually all cells, play crucial role in cell communication and tissue regeneration. However, their short half-life presents challenges for systemic administration. The incorporation of EXs into dECMHs enables localized and prolonged release, thereby enhancing their therapeutic merits. This review thoroughly explains the techniques for decellularization, the characteristics of dECM, as well as the preparation and applications of dECMHs in tissue engineering. It also explores the synergistic effects of EX-dECMH systems on cellular activities essential for tissue repair, including proliferation, differentiation, and neovascularization. The mechanisms of EX release from dECMHs and their applications in the regeneration of skin, intervertebral disc, cartilage, and nerve tissues are elucidated, highlighting the considerable potential of this integrated strategy to improve tissue engineering techniques. Furthermore, the synergistic effect of EX-dECMH systems in tissue healing is investigated. Finally, the limitations associated with the clinical application of EX, dECM, and dECMH as well as the future prospect are included.