Precise Design of Alginate Hydrogels Crosslinked with Microgels for Diabetic Wound Healing.

Alginate hydrogel has received great attention in diabetic wound healing. However, the limited tunability of the ionic crosslinking method prevents the delicate management of physical properties in response to diverse wound conditions. We addressed this issue by using a microgel particle (fabricated by zinc ions and coordinated through the complex of carboxymethyl chitosan and aldehyde hyaluronic acid) as a novel crosslinker. Then the cation was introduced as a second crosslinker to create a double crosslinked network. The method leads to the precise regulation of the hydrogel characters, including the biodegradation rate and the controlled release rate of the drug. As a result, the optimized hydrogels facilitated the live-cell infiltration in vitro and boosted the tissue regeneration of diabetic wounds in vivo. The results indicated that the addition of the microgel as a new crosslinker created flexibility during the construction of the alginate hydrogel, adapting for diverse applications during diabetic-induced wound therapy.