Study On Bioactive Scaffolds For Chronic Wound Healing

Caused by multiple factors in the healing process of the wound,it is defined as a wound that does not sustain the wound healing process or does not heal.Common refractory wounds include diabetic ulcers,burns,hemorrhoids,and more.Due to the significant increase in the incidence of refractory wounds in recent years,the long-term high-cost medical care associated with it,the decline in the quality of life of patients and the waste of social resources have made ugly wounds a serious global public health challenge.The difficult healing of diabetic wounds is mainly due to hypoxia,fibroblast and epidermal cell dysfunction,impaired angiogenesis and neovascularization,cellular damage and neuropathy.Traditional wound dressings are expensive,have a low rate of new blood vessels,have a slow rate of wound repair,are prone to scar tissue,and lack the skin's accessory organs in new tissue.Therefore,it is still a major challenge to prepare a novel bioremediation material for rapid healing of diabetic wounds that can overcome these problems.Bioactive glass has shown successful applications in hard tissue and soft tissue repair due to its high biocompatibility and positive biological effects of ionic products.Recent studies have shown that bioactive glass can promote angiogenesis and wound healing in wound repair,but the mechanism of bioactive glass to promote wound repair is not clear,and pure bioactive glass is difficult to use as skin tissue engineering due to its brittle characteristics.Skin substitutes and stents.Electrospun nanofibers show great promise in the field of wound repair due to their biomimetic natural extracellular matrix nanofiber structure,high specific surface area and high porosity.However,due to the complex physiological microenvironment of diabetic wounds,traditional electrospun nanofibers do not achieve a good healing effect when used as a wound dressing.By functionally constructing electrospun nanofibers,compounding with bioactive glass or preparing wound dressings with drug sustained release effect,it is expected to develop a new type of wound dressing for difficult wound repair.In this dissertation,58 s bioactive glass with micro-nanostructure was sucessfully prepared,and the effect and mechanism of bioactive glass on the differentiation of myofibroblasts into adipocytes were systematically investigated.Type ? collagen/polycaprolactone/bioactive glass composite nanofibers were prepared by combining with conventional electrospinning technology.The effect of this composite scaffold on the repair of diabetic wounds was systematically evaluated,and its repair mechanism was further studied.In addition,in order to diagnose the hypoxic environment of diabetes in the study,the coaxial electrospinning nanofibers with DMOG were prepared,which solved the problem that the repair factor could not be expressed normally during the repair of diabetic wounds.The main research work and results are as follows:(1)Using dodecylamine as a template,a 58 s bioactive glass with good dispersibility was prepared.The effects of different concentrations of 58 s bioactive glass on the secretion of BMP-2 by macrophages and the differentiation of myofibroblasts into adipocytes were studied and verified by in vivo experiments.The results showed that bioactive glass can promote the secretion of BMP-2 by the cells in the situation,thus promoting the differentiation of myofibroblasts into adipocytes.Further studies on the molecular mechanism of BMP-2 promoting the differentiation of myofibroblasts into adipocytes showed that BMP-2 can promote the differentiation of myofibroblasts through SMAD1 and P38 signaling pathways,and inhibit these two signaling pathways to inhibit fat cells.form.At the same time,in vivo experiments further proved that the addition of bioactive glass can promote the differentiation of myofibroblasts into adipocytes during wound repair,thus effectively reducing scar tissue and promoting wound repair.(2)Ttype ? collagen,polycaprolactone and bioactive glass combined nanofiber scaffolds were fabricated using electrospinning technology.The effect of the composite scaffold on endothelial cells was investigated,and the effect of the scaffold on wound healing in diabetic rats was studied.The HIF-1?/VEGF signaling pathway was studied in the case of composite material promoting angiogenesis during wound repair.It was demonstrated that bioactive glass composite nanofiber materials can promote vascular regeneration in difficult wounds through HIF-1?/VEGF signaling pathway.(3)The composite nanofiber with inner layer loaded with DMOG was prepared by coaxial electrospinning technology.The effects of the composite nanofibers on fibroblasts in high glucose environment were studied,including the effects of HIF-1? and its downstream genes and wound repair related genes,and further in vivo experiments were conducted.The results showed that the composite nanofiber scaffold loaded with DMOG in the inner layer could effectively stabilize the expression of HIF-1? in high glucose environment in vitro and promote the up-regulation of related gene expression.Animal experiments have shown that the composite scaffold can also stabilize the expression of HIF-1? in vivo and promote angiogenesis and re-epithelialization of wounds.In summary,bioactive glass can promote the expression of BMP-2 and activate P38 and SMAD signaling pathways,thereby promoting the differentiation of myofibroblasts during wound repair and promoting wound healing.Further,a composite nanofiber scaffold was prepared by combining bioactive glass with polycaprolactone and type ? collagen,which proved that the scaffold can activate HIF-1?/VEGF signaling pathway,promote angiogenesis in diabetic wounds,and improve ischemia in diabetic wounds.Microenvironment.By preparing the composite nanofibers with coaxial loading DMOG,the expression of HIF-1? was stabilized in vitro and in vivo to ensure the homeostasis of HIF-1? in the repair process of diabetic wounds,and then promote the regeneration of wound vessels and epidermis.This paper clarifies the mechanism of bioactive glass to promote wound repair,and studies the mechanism of various nanofibers to promote the repair of refractory wounds,further optimizes the refractory wound dressing and better predicts the material in the wound microenvironment in the refractory wound.