Development And Characterization Of Functional Nanosheet For Chronic Wounds Healing

When the wound is affected by serious bacterial infection or endogenous diseases such as diabetes,it could not be healed through the patient’s own repair system,and would then turn into chronic wound.As a result of persistent abscess and ulcers,the wound usually appears to be uneven and with complex morphology.It is easy to cause local tissue necrosis without external intervention treatment,and severe cases will lead to large area of tissue resection,amputation even death.The existing chronic wound dressings such as gauze,foam dressing,hydrogel dressing,et al,cannot adhere firmly to complex wound morphology due to their poor flexibility and expose the wound when falling off.Therefore,it is a great clinical significance to develop a wound dressing that can adhere to complex chronic wound firmly.Nanosheet is a kind of thin film with a nanoscale thickness and aspect ratio more than 10~6.The large aspect ratio gives the nanosheet excellent flexibility,which can be"seamlessly"fitted to any surface shape and firmly adhered to the surface by physical forces.In this study,the nanosheets were fabricated by biomaterials with good biocompatibility and abundant reaction sites through spin-coating method.By optimizing preparation process,the ideal thickness of nanosheet was obtained,and its physical and chemical properties were characterized.The adhesion mechanism of nanosheet was briefly discussed,and the effects of thickness and surface morphology on the adhesion of nanosheet were revealed.The results showed that the prepared nanosheets have excellent adhesion property to wet tissue with complex morphology,and could maintain firm adhesion under wound stress.On this basis,two common chronic wounds,diabetic foot and bacterial infection wound surface,were taken as objects,and the nanosheets were functionalized with the ability to adapt repair requirements of different types of chronic wounds.Firstly,aiming at the problem of wound healing caused by diabetic vascular lesions,the vascularization promoting peptide was modified to the silk fibroin nanosheet with good mechanical properties to obtain vascularization promoting silk fibroin nanosheet(QSN).QSN has excellent biocompatibility with human umbilical vein endothelial cells(HUVEC),and could promote the expression of angiogenesis markers of HUVEC.In vivo experiments of diabetic mice model showed that QSN could firmly adhere to wound and promote wound re-epithelialization,angiogenesis and wound healing.Moreover,the skin realized regeneration after 21 days.QSN provides a convenient and effective strategy for complex morphology diabetic ulcer repair.Subsequently,for chronic wound caused by bacterial infection,antimicrobial peptide was grafted on nanosheet to fabricate antimicrobial collagen nanosheet(KCN)through click reaction.In vitro antibacterial experiments showed that the KCN could kill over 99%of common bacteria and presented broad spectrum of high antibacterial activity and good biocompatibility.KCN was further applied to the skin bacterial infected wound in SD rats.The results showed that KCN could adhere to the wound firmly,and had fast and lasting anti-infection ability in the wound.Wound healing was basically realized after 14 days.KCN could provide a reliable repair plan for the chronic wound caused by bacterial infection.In conclusion,this study developed a series of functional nanosheet dressings based on its excellent adaptability to the surface of complex wound morphology.The nanosheets could effectively achieve the repair of chronic wounds caused by diabetic ulcer and bacterial infection.This kind of convenient and effective wound dressing is expected to be used as an advanced auxiliary treatment method to provide a new solution for the clinical chronic wound healing,which has very important theoretical significance and broad application prospect.