Functionalized gelatin/strontium hydrogel bearing endothelial progenitor cells for accelerating angiogenesis in wound tissue regeneration

Abstract

While polymer hydrogels are frequently utilized as wound dressings, they lack the sufficient bioactivity necessary to promote re-epithelialization and angiogenesis. In this work, a therapeutic angiogenesis complex is developed using a mixture of dopamine-modified polyhedral oligomeric silsesquioxane (Dopa-POSS), strontium ions (Sr²⁺ ions) photocrosslinked gelatin methacryloyl (GelMA) hydrogel and endothelial progenitor cells (EPCs) for full-thickness burn wound healing. Dopa-POSS is used to reinforce the hydrogel, and Sr²⁺ ions stabilizer is densely incorporated inside the network of GelMA hydrogels by ultraviolet cross-linking, thus effectively enhancing the hydrogel mechanical strength. The multifunctional GelMA hydrogels comprised gelatin's arginine-glycine-aspartate (RGD) patterns and active Sr²⁺ ions that promote EPC biological activity and proliferation. Notably, the Sr²⁺ ions in the functional hydrogels substantially enhanced EPC proliferation in a three-dimensional environment, migration, and angiogenesis-related protein expression. After 14 days, the Gel/Sr²⁺@POSS/EPCs composite hydrogel substantially accelerates and enhances the new blood vessel development process, collagen deposition, and re-epithelialization with the almost closed wounds and newly created tissue. Thus, UV-crosslinked Gel/Sr²⁺@POSS hydrogels functionalized with EPCs can be a potentially beneficial therapeutic system for full-thickness burn wound healing.

Keywords: Burn wound healing; Endothelial progenitor cells; GelMA; Hydrogel; Strontium.