摘要
Diabetic chronic wound,characterized by prolonged inflammation and impaired angiogenesis,has become one of the most serious challenges in clinic and pose a significant healthcare burden worldwide.Although a great variety of wound dressings have been developed,few of encouraged achievements were obtained so far.In this study,the gene-activated strategy was applied to enhance sustained expression of vascular endothelial growth factor(VEGF)and achieve better healing outcomes by regulating inflammation and promoting angiogenesis.The gene-activated bilayer dermal equivalents(Ga-BDEs),which has good biocompatibility,were fabricated by loading the nano-sized complexes of Lipofectamine 2000/plasmid DNA-encoding VEGF into a collagen-chitosan scaffold/silicone membrane bilayer dermal equivalent.The DNA complexes were released in a sustained manner and showed the effective transfection capacities to up-regulate the expression of VEGF in vitro.To overcome cutaneous contraction of rodents and mimic the wound healing mechanisms of the human,a reformative rat model of full-thickness diabetic chronic wound was adopted.Under the treatment of Ga-BDEs,speeding wound healing was observed,which is accompanied by the accelerated infiltration and phenotype shift of macrophages and enhanced angiogenesis in early and late healing phases,respectively.These proved that Ga-BDEs possess the functions of immunomodulation and pro-angiogenesis simultaneously.Subsequently,the better regeneration outcomes,including deposition of oriented collagen and fast reepithelialization,were achieved.All these results indicated that,being different from traditional pro-angiogenic concept,the up-regulated expression of VEGF by Ga-BDEs in a sustained manner shows versatile potentials for promoting the healing of diabetic chronic wounds.
基金
financially supported by the National Natural Science Foundation of China(51873184,81671918)
National Key R&D Program of China(2016YFC1101000).
