Construction Of Double-layer Anti-adhesion Nano-electrospun Membrane Based On Graphene Oxide And Its Application In Repair Of Abdominal Wall Defects

Objective: Abdominal wall defects caused by trauma,tumor resection,infection,and incisional hernia are common clinical problems.Traditional synthetic meshes are prone to complications such as bowel adherence,intestinal obstruction and chronic pain due to their non-degradability.The biologic meshes,although biocompatible,has poor mechanical properties and a high recurrence rate of hernia.Graphene oxide(GO)is one of the carbon nanomaterials with highest hardness.Mixing it with other materials can improve the mechanical properties.Chitosan(CS),a natural component in shells or other crustaceans,has the advantage of hemostasis,antibacterial and anti-adhesion.Therefore,we hope to prepare a patch based on the above two materials,which can prevent the formation of hernia and adhesion,for the repair of abdominal wall defects.At the same time,effective method which can promote the repair of tissue defects was explored in our study,so as to provide a reference for clinicians.Method: Polycaprolactone(PCL)was used as the basic component,outer scaffolds(GO-PCL)with different concentrations of GO(0.1,0.5,1.0%w/v)were first prepared by electrospinning technology,and a series of identifications were performed to screen out the optimal concentration for subsequent experiments.On this basis,the inner scaffold(CS-PCL)was prepared,and directly covered the surface of the GO-PCL scaffold.Finally,the carboxyl group in NAC was cross-linked with the amino group in CS to form an amide bond,thereby preparing a drug-loaded composite double-layer scaffold(GO-PCL/ NAC-CS-PCL).In this study,the morphology of the scaffold was observed using scanning electron microscopy.The feasibility of preparing and applying the scaffold in vivo was discussed through Raman spectroscopy,elastic modulus detection,drug release test,and cell compatibility test.Simple PCL,GO-PCL,and GO-PCL/CS-PCL scaffolds were used as controls,and the repair effect of abdominal wall defects of GO-PCL/NAC-CS-PCL scaffolds was studied.Result: The results showed that the 0.1%GO-PCL/NAC-CS-PCL composite double-layer scaffold was successfully constructed in our study.The scaffold had a nano-scale network structure.When deformed at 20% within the range,the elastic modulus of 0.1%GO-PCL/NAC-CS-PCL scaffold was about two times higher that of the simple PCL scaffold.On this scaffold,the cells adhered well and stretched in shape,showing good proliferation ability.When the scaffolds were applied to repair the abdominal wall defects in rats,no hernia formation was observed in the 0.1%GO-PCL/NAC-CS-PCL scaffold group,and adhesion formation was less,the adhesion score was 1.50 ± 0.50 points.Moreover,compared with the 0.1%GO-PCL/CS-PCL scaffold group,the 0.1%GO-PCL/ NAC-CS-PCL scaffold group had more neo-collagen deposition,and CD31 staining results showed that neovascularization was visible in the center area of the scaffold.Conclusion: This study demonstrated that the 0.1%GO-PCL/NAC-CS-PCL scaffold had provide a new choice for the repair of abdominal wall defects due to its good mechanical properties,in vitro biocompatibility,as well as the repair effect of abdominal wall defects in rats.