Exo-hydrogel therapy: a revolutionary approach to managing diabetic complications

This review systematically examines the transformative potential of Exosome-hydrogel (Exo-gel) composite systems in combating diabetic complications, with a particular emphasis on their macromolecular interactions and therapeutic implications. By synergistically integrating the bioactive cargo of Exos with the structural tunability of polysaccharide-based hydrogels, this advanced biomaterial platform addresses critical limitations in conventional therapies through the spatiotemporally controlled delivery of regenerative factors. We highlight how the dynamic interplay between natural biopolymers and exosomal surface proteins enhances extracellular matrix (ECM) remodeling while maintaining bioactive stability, a crucial advancement for chronic diabetic conditions. A comprehensive analysis reveals that Exo-gel systems demonstrate therapeutic efficacy in three key pathological contexts: (1) neural regeneration via Schwann cell modulation, (2) angiogenesis restoration through VEGF/VEGFR signaling pathways, and (3) chronic wound healing mediated by macrophage polarization. Our critical appraisal of preclinical evidence positions Exo-gel technology as a paradigm-shifting approach in diabetes care, offering solutions to current challenges in sustained drug delivery and targeted tissue regeneration, while outlining future translational pathways for bioengineered therapeutic systems.