Curcumin-loaded Electrospun Composite Nanofiber Mesh For Abdominal Wall Defect Repair

Background: Abdominal wall hernia repair surgery is a common surgical procedure,which has been increasing year by year,and more than one million hernia meshes are required to implant worldwide each year.With the development of abdominal wall surgery and minimally invasive techniques,intraperitoneal onlay mesh(IPOM)technique,since introduced,has become one of the most commonly used surgical methods for modern abdominal wall hernia surgery.However,of note,with the use of IPOM technique,the mesh would inevitably come into direct contact with the abdominal viscera and result in peritoneal adhesion,which,if not treated,may lead to serious postoperative complications such as infection,chronic pain,mesh erosion,intestinal obstruction and intestinal perforation.Objective: Curcumin-loaded composite meshes were prepared by the electrospinning technique,the anti-adhesion effect and inflammatory response of this novel composite mesh were observed and studied in rats.Methods: First,curcumin-loaded gelatin nanofiber membranes were prepared by electrospinning technology,which were bonded to the surface of polypropylene meshes.Then,the physical properties of composite mesh were characterized by scanning electron microscopy and mechanical property determination etc.Apart from that,in vitro release test was performed to detect the release of curcumin from composite meshes.In addition,the CCK-8 kit was used to test the in vitro cytotoxicity of meshes and live cell staining was performed to determine fibroblast proliferation on composite mesh.Relevant inflammatory factors were also detected.Finally,the rat abdominal wall defect model was constructed and 18 male rats were randomly divided into three groups: polypropylene group,polypropylene + clodronate liposome macrophage-depleted treatment group,and curcumin-loaded composite mesh group.The peritoneum and abdominal muscle tissue layers of rats were removed,and the skin and subcutaneous tissue layers preserved,to create full-thickness abdominal wall defects.Then the defects were repaired with polypropylene meshes or curcumin-loaded composite meshes using an IPOM technique.All rats were sacrificed at 4 weeks after surgery and the tissue specimens were harvested.Differences of the infiltration level of macrophages and other inflammatory cells and the level of inflammation among groups were compared by hematoxylin and eosin(H&E)staining and immunohistochemical staining.Results: Scanning electron microscopy micrographs showed that curcumin-coated composite meshes were successfully constructed by attaching curcumin-loaded gelatin electrospinning nanofibrous membranes,with randomly interwoven network structure,to the surface of the polypropylene meshes.The electrospinning fiber morphology was uniform and smooth,and no obvious scattered beads was present.The diameter of electrospinning fibers ranged from 171 nm to 993 nm,and the average diameter was 339.11 nm ± 15.77 nm,which meet the nanofiber standard.Curcumin-coated composite meshes possessed similar mechanical properties with polypropylene meshes and were non-toxic to fibroblasts in vitro.Fibroblasts could proliferate and grow on the curcumin-coated composite meshes.The expression level of inflammatory factors MCP-1 and p-STAT3 were down-regulated.In vitro release curve of curcumin demonstrated that the dissolution rate of curcumin from curcumin-coated composite meshes significantly improved compared with free curcumin powder.A sustained release of curcumin from curcumin-coated composite meshes was observed over time.Experiments on abdominal wall defects repair in rats presented that,compared with polypropylene group,curcumin-loaded composite mesh group could effectively inhibit the infiltration of macrophages and alleviate inflammation responses,thus reducing the deposition of fibrin and preventing adhesions formation between mesh and abdominal tissues.Experimental results of the polypropylene + clodronate liposome macrophage-depleted treatment group further confirm this.Conclusion: Curcumin-loaded composite meshes possessed excellent physical properties and good biocompatibility,the novel mesh could significantly inhibit the infiltration of macrophages,alleviate inflammation responses and present good anti-adhesion effect,which could meet the requirements of abdominal wall defect repair.