Research On Wound Healing Under Mechanical Force By Macrophage Polarization Intervention

ObjectivesMechanical force and wound inflammation are two key factors that affect wound healing.Abnormal mechanical environment and excessive inflammation often lead to pathological scar,and even chronic wounds formation.However,whether the mechanical force and skin inflammation can interact,the interaction mechanism is not clear.The aim of this study was to investigate mechanical force to regulate the inflammatory response of cutaneous wounds,thus affecting the possible mechanism of wound repair and to find therapeutic targets.And then to explore a good way to promote the wound healing through small molecule drug intervention,.MethodsIn this study,the mouse monocyte/macrophages line(Raw264.7)were stimulated by the Flexcel-5000 cell mechanical loading system,and the M1/M2 macrophage polarization-related markers CCR7,i NOS and CD206,Arg1 were detected by real-time fluorescence quantitative PCR and immunofluorescence respectively.In vivo study,the number of macrophages and the polarization were detected by special staining and immunofluorescence staining.The expression of NF-κB signaling pathway was detected by Western blot.In the intervention study,the mouse hypertrophic scar model was induced by mechanical force,and the samples were collected by real-time fluorescence quantitative PCR,Western blot,histology and immunohistochemistry.ResultsIn vitro studies have shown that mechanical force promoted Raw264.7 cells differentiate to M1,and proinflammatory cytokines increased.Furthermore,through the mouse wound repair model,we found that mechanical stimulation led to increased number of macrophages in the wound tissue,M1 polarization enhanced,inflammation increased,wound healing process delayed.Mechanisms study have shown that mechanical force significantly activate macrophage NF-κB signaling pathways.The intervention study found that small molecule compounds naringenin can reduce the mechanical force induced skin inflammation and inhibit mouse skin hypertrophic scar formation.ConclusionsThis study demonstrates that mechanical force regulates macrophage polarization by activating NF-κB signaling pathways that affect skin repair processes.Naringenin can improve wound inflammation and inhibit hypertrophic scarring,which can be used as a potential drug or drug precursor for the treatment of hypertrophic scars.