Novel cocktail therapy based on multifunctional supramolecular hydrogel targeting immune-angiogenesis-nerve network for enhanced diabetic wound healing

Diabetes-associated chronic skin wounds present a formidable challenge due to inadequate angiogenesis and nerve regeneration during the healing process. In the present study, we introduce a groundbreaking approach in the form of a novel cocktail therapy utilizing a multifunctional supramolecular hydrogel. Formulated through the photo-crosslinking of gelatinized aromatic residues and β-cyclodextrin (β-CD), this injectable hydrogel fosters weak host-guest interactions, offering a promising solution. The therapeutic efficacy of the hydrogel is realized through its integration with adipose-derived stem cells (ADSCs) and lipid nanoparticles encapsulating ginsenoside RG1 and Stromal cell-derived factor-1 (SDF-1). This strategic combination directs ADSCs to the injury site, guiding them toward neurogenic specialization while establishing an advantageous immunomodulatory environment through macrophage reprogramming. The synergistic effects of the newly differentiated nerve cells and the regenerative cytokines secreted by ADSCs contribute significantly to enhanced angiogenesis, ultimately expediting the diabetic wound healing process. To summarize, this innovative hydrogel-based therapeutic system represents a novel perspective for the management of diabetic wounds by concurrently targeting immune response, angiogenesis, and nerve regeneration—a pivotal advancement in the quest for effective solutions in diabetic wound care.