Modulation Of Macrophages By A Paeoniflorin-loaded Hyaluronic Acid-based Hydrogel Promotes Diabetic Wound Healing

Under normal physiological state,skin wound will undergo hemostasis,inflammation,proliferation and remodeling for rapid and orderly healing.However,in the presence of diabetes and other chronic diseases,the inflammatory phase of wound healing is prolonged,and complications such as cellular dysfunction and angiogenesis disorders occur,resulting in chronic wounds,which complicate medical care and increase treatment costs.At present,the treatment of diabetic wound is limited,and the effect is not ideal.Therefore,new treatment methods and means are still needed.Macrophages play a key role in tissue repair and regeneration.It was found that macrophages in diabetic wounds maintain a continuous pro-inflammatory phenotype,leading to a prolonged inflammatory period during wound healing.This phenomenon provides a new idea for regulating macrophages to promote diabetic wound healing.In this study,Paeoniflorin（PF）,a Chinese herbal monomial compound with the potential to regulate macrophages,was screened and identified by ELISA,cell viability detection and other experimental means,which can reduce the production of pro-inflammatory factors without causing cytotoxicity to skin tissue cells.Secondly,the ability of PF to regulate macrophages was confirmed by in vitro experiments.This ability is mainly manifested in two aspects:on the one hand,PF can regulate the phenotype of macrophages and improve the ratio of M2-type macrophages to M1-type macrophages;On the other hand,PF can regulate the function of macrophages:it can down-regulate the expression of pro-inflammatory factors related to M1-type macrophages at the gene,molecular and protein levels,and up-regulate the expression of anti-inflammatory factors related to M2-type macrophages.Thirdly,the therapeutic effect of PF on diabetic wounds was further explored by establishing a full-layer skin injury model in diabetic mice Based on previous studies in the laboratory,this study constructed a PF-loaded hyaluronic acid hydrogel preparation（HA-PF）,which confirmed that the preparation could significantly promote the healing of diabetic wounds,and the promoting healing effect was closely related to the ability of PF to regulate macrophages in diabetic woundsFinally,through immunofluorescence staining,H＆E staining and Masson staining of skin tissue,this study further confirmed that HA-PF can achieve the effect of treating diabetic wounds by regulating macrophages in diabetic wounds.It provides a new therapeutic method for diabetic wound healing and has certain clinical transformation potential.