Organic/Inorganic Composite Electrospun Fibrous Membrane For Skin Wound Repair

Acute or chronic skin damage caused by injury or disease poses a serious threat to human survival and health.Therefore,there is a great demand for the clinical skin repair materials.Unfortunately,the existing skin repair materials are poor in biological activity,complex in production processes and high in costs,so there is an urgent need to explore new skin repair materials.The ideal skin repair material should have two functions:skin structure simulation and skin tissue regeneration.It was found that the organic/inorganic composite electrospun fibrous membrane prepared by electrospinning can not only simulate the fibrous structure in the natural extracellular matrix(ECM)of the human body but release beneficial active ions,which not only help to regulate the traumatic microenvironment,but also promote wound repair.The extant research,which usually used traditional random electrospun fiber or one-way electrospun fiber,cannot simulate the multi-level structure of the human skin to a high degree.As a result,the effect of wound healing is not ideal.In addition,even though silica-based bioactive ceramics have a wide range of research in hard tissue repair,there are few studies on inorganic bioactive ceramics used in soft tissue repair.The use in soft tissue repair is likewise limited.Thus it is significant to conduct more such research.In this paper,the nanofibrous membrane with controllable pattern,multi-stage pore structure and surface silicon-based bioactive glass were prepared to examine their effect on the repair of acute wounds in the skin.At the same time,the micro-composite fibrous with silica-based bioactive ceramics was prepared to study its impact on chronic diabetic wound healing,and to explore its mechanism of action.This study provides a new method for the preparation of organic/inorganic composite electrospun fibrous membrane and lends theoretical support for the application of silicon-based inorganic bioactive materials in the field of skin repair.The main contents of this thesis include the following two parts:(1)First,the function of organic/inorganic composite electrospun fibrous membranes PT-NBG to promote acute wound healing was studied.Poly(e-caprolactone)PCL,D,L-poly(lactic acid)(PDLLA)and inorganic silicate biologically active ceramics(Akermanite,Ca2MgSi2O7)were used as raw materials.PT-NBG with controlled structure,multi-stage pore structure and surface silicon-based bioactive glass was prepared by combining electrospinning and pulsed laser deposition(PLD).The results showed that the nanometer bioactive glass(NBG)containing Ca,Mg and Si elements was deposited on the surface of nanofibrous membranes after laser ablation,and the hydrophobicity and cell adhesion of the organic polymer fibrous membranes were improved,which was more conducive to human umbilical vein endothelial cells(HUVECs),spread and proliferation.Mouse skin acute wound experiments found that PT-NBG could promote acute skin wound healing,specifically to promote wound angiogenesis,epidermal migration and collagen deposition.The above results showed that bioactive glass and multi-stage micro-pattern fibrous structure could help to promote wound healing.(2)Second,the function and mechanism of organic/inorganic composite fibrous membrane NAG-PL in promoting wound healing in chronic diabetes mellitus was studiedNAG-PL was prepared by using silicate biologically active ceramics(Nagelschmidtite,NAGEL,Ca7Si2P2O16)and polymer PCL and gelatin for the first time.The composite fibrous membranes(NAG-PL)was prepared by using electrospinning technology.The results showed that when the content of NAGEL was 10%(10 NAG-PL),the effect of cell proliferation,migration and adhesion was the best,and it could promote the wound healing of diabetic mice.The vascular network and vascular CD31 staining at the wound site showed that 10 NAG-PL favored the increase in the number of blood vessels and the improvement of the vascular network structure.At the same time,10 NAG-PL had the role of promoting re-epithelialization and collagen deposition.Subsequent studies had shown that NAGEL could play a role in activating epithelial-mesenchymal transition(EMT)and endothelial-to-mesenchymal transition(EndMT)signaling pathway.The above experimental results showed that silicate bioactive ceramics had a good effect of promoting chronic wound healing,and thus had potential clinical application value in the field of diabetic wound repair.In summary,two organic/inorganic composite electrospun fibrous membranes were prepared and their role in skin wound repair were studied.In the preparation of composite materials,micro-pattern electrospinning and pulsed laser deposition method were used,integrating the material structure and bioactive glasses so as to promote the wound repair.New method was developed for the design of a new type of specific composition and orderly structure of biological materials.According to the experimental results,it could be concluded that both the silicate bioactive glass and the silicate bioceramics had shown excellent efficiency for the healing of acute or chronic wound.It laid the foundation for the use of silicon-based biomaterials in the regeneration of tissues.