An Extracellular Matrix-Mimicking Hydrogel for Full Thickness Wound Healing in Diabetic Mice

Abstract

An extracellular matrix-mimicking hydrogel is developed consisting of a hyaluronan-derived component with anti-inflammatory activity, and a gelatin-derived component offering adhesion sites for cell anchorage. The in situ-forming hyaluronan-gelatin (HA-GEL) hydrogel displays a sponge-like microporous morphology. Also, HA-GEL shows a rapid swelling pattern reaching maximum weight swelling ratio within 10 min, while at the equilibrium state, fully swollen hydrogels display an exceedingly high water content with ≈2000% of the dry gel weight. Under typical 2D cell culture conditions, murine 3T3 fibroblasts adhere to, and proliferate on top of the HA-GEL substrates, which demonstrate that HA-GEL provides a favorable microenvironment for cell survival, adhesion, and proliferation. In vivo healing study further demonstrates HA-GEL as a viable and effective treatment option to improve the healing outcome of full thickness wounds in diabetic mice by effectively depleting the inflammatory chemokine monocyte chemoattractant protein-1 in the wound bed.

Keywords: anti-inflammation; diabetic wound healing; extracellular matrix; hydrogel.