Zinc alginate hydrogels with embedded RL-QN15 peptide-loaded hollow polydopamine nanoparticles for diabetic wound healing therapy
Huiling Sun, Ying Yang, Yutong Wu, Zhe Fu, Yue Zhang, Yixiang Liu, Junxu Nie, Yinglei Wang, Yinglei Wang, Huichao Wang, Bingjie Mai, Nuo Fu, Chao Li, Naixin Liu, Yilin Li, Ziwei Deng, Li He, Ying Wang, Ying Wang, Xinwang Yang
Abstract
Chronic wound healing remains a considerable clinical challenge worldwide. We previously identified a pro-regenerative agent, i.e., hollow dopamine nanoparticles (HPDA) loaded with potent pro-healing peptide RL-QN15 (HPDAlR), with significant skin wound healing activity. In the current study, in consideration of clinical application, we successfully prepared a new zinc alginate hydrogel embedded with HPDAlR (HPDAlR&ZA) to treat diabetic wounds. HPDAlR&ZA exhibited no obvious toxicity against keratinocytes, human umbilical vein endothelial cells (HUVECs), human skin fibroblasts (HSFs), and mice. HPDAlR&ZA significantly promoted keratinocyte, HUVEC, and HSF proliferation, as well as HUVEC migration and angiogenesis. HPDAlR&ZA also modulated the expression of cytokines from macrophages. Diabetic mouse full-thickness skin wound and diabetic patient in vitro skin wound models showed that HPDAlR&ZA resisted the inflammatory response by rapidly polarizing M1 macrophages to M2 macrophages, thereby reconstructing blood supply, increasing collagen deposition, and accelerating diabetic wound repair and skin regeneration. In summary, HPDAlR&ZA is a biodegradable hydrogel wound dressing and an efficient treatment strategy for diabetic wound repair, with strong anti-oxidant, anti-inflammatory, and pro-angiogenic features.