Rapid repair of large skin wounds is one of the current clinical challenges,and the development of materials with good properties to promote skin wound repair is a hot research topic in the biomedical field.Marine origin collagen has become a popular material in biomedical field in recent years due to its good physicochemical properties and biocompatibility.Tilapia skin is rich in collagen andω-3 polyunsaturated fatty acids(ω-3PUFA),which are mostly by-products of aquatic processing and are inexpensive,and is a biological raw material with great potential for application.In this study,tilapia acellular dermal matrix(TADM)with good physicochemical properties and biocompatibility was prepared,and the effect of TADM in promoting wound repair was verified by SD rat acute skin injury model,and finally the potential acute skin wound repair mechanism of TADM was explored and analyzed by a systems biology approach.(1)Preparation and property characterization of TADM.In this part of the study,TADM was prepared by sodium hydroxide(Na OH)degreasing,hydrogen peroxide(H2O2)bleaching,sodium chloride(Na Cl)and Na OH decellularization using tilapia skin as raw material.1)The physicochemical properties of TADM were determined by H&E staining,scanning electron microscopy,fourier infrared spectroscopy,universal test machine,hydroxyproline content and porosity determination,etc.2)The biocompatibility and biosafety of TADM were determined by in vivo degradation,cytotoxicity,pyrogen,hemolysis and skin sensitization tests.The results showed that the TADM obtained by alkali degreasing and decellularization was mainly composed of type I collagen,with porous lamellar structure(dense and sparse layers),good mechanical properties(average maximum tensile strength of 21.76±3.84 MPa,average elongation at break of 39.89±9.00%),high porosity(82.51±7.12%)and swelling rate(1549±121.37%),and no intradermal irritation reaction,cytotoxic reaction,pyrogenic reaction,hemolysis,and sensitization reaction in rats.(2)The effect of TADM on the repair of acute skin wounds in SD rats.This part of the study was conducted based on the construction of a prepared SD rat acute skin allograft model,which was evaluated pathologically by observing its wound healing effect,H&E staining of tissue samples,Masson staining and immunohistochemical staining.The results showed that TADM could cause rapid granulation and epithelialization of skin wounds and significantly increased the expression of EGF,FGF,CD31 and NGF factors while promoting the production and deposition of new skin collagen.TADM had a significant effect on the healing of acute skin wounds.(3)Potential mechanisms of TADM for repairing acute skin wounds.Numerous studies have shown thatω-3PUFA has good maintenance and disease repair effects on skin.This part of the study initially explored the potential mechanism of action ofω-3PUFA components(ALA,DHA,EPA)enriched in TADM in promoting skin wound repair through network pharmacology,bioinformatics and molecular docking.The molecular docking results showed thatω-3PUFA has strong binding energy(<-5kcal/mol)to several core targets such as VEGFA,CDC42,HIF1A,CXCR4 and RAC1,and theω-3PUFA in TADM may have at least the role of promoting angiogenesis and innervation,and its action process may be related to cell migration,angiogenesis and innervation,etc.A variety of relevant signaling pathways are involved.Therefore,the results of this system demonstrate that TADM has good physicochemical properties,biocompatibility and ability to promote acute skin wound repair,and has the potential to be able to solve the repair challenges currently faced in the clinic. |