The Study Of The Treament Of Puerarin-loaded Hydrogel Mesh For Pelvic Organ Prolapse

Objective:To investigate the effect of puerarin(Pue)loaded methacrylic anhydride gelatin(GelMA)mesh for female pelvic organ prolapse.Methods:Collect the human vaginal fibroblasts(HVFs)from the patients of pelvic organ prolapse(POP),and using Western Blot,RT-PCR,ELISA to test the expression levels of MMPs,oxidative stress factor ROS,and inflammatory factor in HVFs,respectively.Using UV-crosslinking method to prepare the covalently cross-linked hydrogel,Pue loaded GelMA(Pue@GelMA),and investigate the characterizations like drug-loading ability and biocompatibility.In vitro,to evaluate the effects of Pue@GelMA of HVFs,the proliferation activity,inflammatory factors and collagen expression were investigated.For in vivo study,we established animal model of rabbit abdominal wall defect,and repaired with Pue@GelMA mesh.The repair of the defect was observed by HE.The expression levels of inflammatory factors,collagen and MMPs were evaluated by RT-PCR and western blotting in vivo and in vitro.Results:1)The pelvic floor of POP is in an oxidative stress state and inflammatory microenvironment,the expression of MMPs is significantly increased,which leading the collagen degradation.2)GelMA showing great biocompatibility,which has the average pore size of 52.97 ± 2.23 μm,the swelling rate of up to 550%,sustained release of the drug to 2 months,and degradation more than 8 weeks.3)In vitro,Pue@GelMA significantly down-regulated the expression of IL-3,IL-6 and MMP 2/9(P<0.01)and increased the expression of COL-1(P<0.01).4)In vivo,Pue@GelMA can effectively inhibit the inflammatory response caused by mesh implantation,and promote the repair of rabbit abdominal wall defect.Conclusion:Puerarin-loaded methacrylic anhydride gelatin hydrogel mesh can not only promote the regeneration and repair of pelvic floor tissue,but also effectively avoid serious complications such as mesh erosion and chronic inflammation,which provides a new strategy of biological material treat pelvic organ prolapse.