Modulation of macrophages by a paeoniflorin-loaded hyaluronic acid-based hydrogel promotes diabetic wound healing

• Published in: Materials today bio Vol. 12; p. 100139
• Main Authors: Yang, Hao, Song, Liu, Sun, Bingxue, Chu, Di, Yang, Leilei, Li, Meng, Li, Huan, Dai, Yun, Yu, Zhuo, Guo, Jianfeng
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.2021; Elsevier
• Subjects: Angiogenesis; Anti-inflammation; Full Length; Hydrogel; Macrophage polarization; Regenerative medicine; α-smooth muscle actin; interferon-γ; Regenerative medicine; N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride; phosphate-buffered saline; integrated optical density; interleukin-10; paeoniflorin; signal transducer and activator of transcription; Anti-inflammation; hyaluronic acid; inducible nitric oxide synthase; interleukin-1β; Angiogenesis; dimethyl sulfoxide; bone marrow-derived macrophages; penicillin-streptomycin; scanning electron microscopy; polyvinylidene difluoride; Macrophage polarization; fetal bovine serum; streptozocin; transforming growth factor-β; tumor necrosis factor-α; human umbilical vein endothelial cells; swelling ratio; Hydrogel; lipopolysaccharide; macrophage colony-stimulating factor; Adipic acid dihydrazide; arginase 1; fetal bovine serum, FBS; interleukin-10, IL-10; tumor necrosis factor-α, TNF-α; interferon-γ, IFN-γ; polyvinylidene difluoride, PVDF; lipopolysaccharide, LPS; signal transducer and activator of transcription, STAT; α-smooth muscle actin, α-SMA; paeoniflorin, PF; streptozocin, STZ; swelling ratio, SR; phosphate-buffered saline, PBS; Adipic acid dihydrazide, ADH; N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride, EDC.HCl; hyaluronic acid, HA; transforming growth factor-β, TGF-β; arginase 1, Arg-1; bone marrow-derived macrophages, BMDMs; penicillin-streptomycin, P/S; integrated optical density, IOD; scanning electron microscopy, SEM; interleukin-1β, IL-1β; macrophage colony-stimulating factor, M-CSF; dimethyl sulfoxide, DMSO; human umbilical vein endothelial cells, HUVECs; inducible nitric oxide synthase, iNOS
• ISSN: 2590-0064; 2590-0064
• DOI: 10.1016/j.mtbio.2021.100139

The impaired wound healing in diabetes is a central concern of healthcare worldwide. However, current treatments often fail due to the complexity of diabetic wounds, and thus, emerging therapeutic approaches are needed. Macrophages, a prominent immune cell in the wound, play key roles in tissue repair and regeneration. Recent evidence has demonstrated that macrophages in diabetic wounds maintain a persistent proinflammatory phenotype that causes the failure of healing. Therefore, modulation of macrophages provides great promise for wound healing in diabetic patients. In this study, the potential of paeoniflorin (PF, a chemical compound derived from the herb Paeonia lactiflora) for the transition of macrophages from M1 (proinflammatory phenotype) to M2 (anti-inflammatory/prohealing phenotype) was confirmed using ex vivo and in vivo experimental approaches. A hydrogel based on high molecular weight hyaluronic acid (HA) was developed for local administration of PF in experimental diabetic mice with a full-thickness wound. The resultant formulation (HA-PF) was able to significantly promote cutaneous healing as compared to INTRASITE Gel (a commercial hydrogel wound dressing). This outcome was accompanied by the amelioration of inflammation, the improvement of angiogenesis, and re-epithelialization, and the deposition of collagen. Our study indicates the significant potential of HA-PF for clinical translation in diabetic wound healing. [Display omitted] •PF modulates the phenotype and function of macrophages from M1 to M2.•The PF-loaded HA-based hydrogel significantly promotes diabetic wound healing.•The healing efficacy results from the capacity of fulfilling the inflammation, proliferation, and maturation stages.