Zinc alginate hydrogels with embedded RL-QN15 peptide-loaded hollow polydopamine nanoparticles for diabetic wound healing therapy. (October 2022)

• Record Type: Journal Article
• Authors: Sun, Huiling; Yang, Ying; Wu, Yutong; Fu, Zhe; Zhang, Yue; Liu, Yixiang; Nie, Junxu; Wang, Yinglei; Wang, Huichao; Mai, Bingjie; Fu, Nuo; Li, Chao; Liu, Naixin; Li, Yilin; Deng, Ziwei; He, Li; Wang, Ying; Yang, Xinwang
• Is Part Of: Materials & design. Volume 222(2022)
• Publication Date: 2022-10
• Subjects: Chronic wound healing -- Diabetic wounds -- Hydrogel wound dressing; Materials -- Periodicals; Engineering design -- Periodicals; Matériaux -- Périodiques; Conception technique -- Périodiques; Electronic journals; 620.11
• DOI: 10.1016/j.matdes.2022.111085
• Languages: English
• ISSNs: 0264-1275

Abstract

Graphical abstract: Highlights: HPDAlR&ZA (a new zinc alginate hydrogel embedded with hollow dopamine nanoparticles (HPDA) loaded with potent pro-healing peptide RL-QN15) promotes cells proliferation, as well as migration and angiogenesis and accelerates the healing rate of chronic skin wounds in diabetes mice. HPDAlR&ZA modulates the expression of cytokines from macrophages. HPDAlR&ZA resists 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. 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.