Macrophage phenotype polarization modulates vascular regeneration in small-diameter graft implantationOA

Background:Small-diameter vascular grafts(<6 mm)are needed but often fail due to postoperative stenosis.Macrophages critically influence graft outcomes by regulating neointima formation and endothelialization.Peritoneal macrophages exhibit high plasticity and can polarize into M1 or M2 types in response to microenvironmental signals.However,how specific macrophage phenotypes drive vascular regeneration under hemodynamic conditions remains unclear.Methods:Primary peritoneal macrophages were polarized into the M1 phenotype via LPS stimulation in vitro.These M0 and M1 macrophages were then seeded onto electrospun PCL grafts,and their roles in vascular regeneration were assessed using a rat abdominal aorta transplantation model.Results:M0 macrophages significantly promote rapid endothelialization and regeneration of functional smooth muscle cells on the graft surface,enhance the structural integrity of the neovascular wall,and significantly improve the long-term patency of the graft.In contrast,M1-type macrophages significantly inhibited the regenerative process and exacerbated neointimal hyperplasia and luminal narrowing.Conclusion:Compared with the unpolarized M0 phenotype,M1 macrophages trigger a more intense inflammatory response that hinders tissue regeneration.Therefore,regulating the polarization of macrophages to the M1 phenotype is a key potential strategy to improve the outcome of small-caliber vascular graft regeneration.Key words:Small-diameter vascular grafts,M0 macrophages,tissue engineering,immune regulation,macrophage polarization,classical activated macrophages(M1),angiogenesis.