A Polypropylene Mesh Coated With Interpenetrating Double Network Hydrogel For Local Drug Delivery In Temporary Closure Of Open Abdomen

Background Open abdomen（OA）is the most effective treatment for abdominal sepsis,abdominal compartment syndrome and abdominal wall defects caused by trauma or surgery.Prosthetic materials have been widely used for temporary abdominal closure after OA,but local adhesion,local adhesions,bowel rupture and fistula formation caused by current materials seriously affect the quality of life of patients.The hydrogel interior porous structure can mimic the extracellular matrix of native tissue.Hydrogels have been widely used in many biomedical fields such as drug delivery,cell culture,tissue engineering and wound healing due to their good biocompatibility.Objective To design an interpenetrating double-network hydrogel to provide wound protection for temporary abdominal closure in OA.Method An interpenetrating double-network hydrogel by photoinitiating glycidyl methacrylate-conjugated xanthan（XG）and 4-Arm polyethylene glycol thiol.Fourier transform infrared spectroscopy and scanning electron microscopy were used to detect the structure of the hydrogel.The material properties,mechanical properties,cytocompatibility,and drug controlled-release ability of the hydrogel were tested.Twenty four SD rats were randomly divided into control group（pp mesh group）,fibrin film group（fibrin gel/pp mesh group）,hydrogel group（XG/TPEG hydrogel/pp mesh group）,and drug-loaded hydrogel group（VEGF-loaded XG/TPEG hydrogel/pp mesh group）,with 6rats in each group.The rat model of OA was established,and the corresponding patch was sutured to the edge of the defect with 4/0 silk suture in each group.The pathomorphological changes of granulation tissue were observed.The expression of related inflammatory cytokines,CD31 andα-SMA was detected.Measurement data were expressed by Mean±SD deviation.Two independent samples t-test was used for comparison between two groups with equal variance.Rank sum test was used for unequal variance.P<0.05 was considered statistically significant.Results The absorption peak of XG₄TPEG₁₀hydrogel appeared at 665 cm^-1.The hydrogel has a three-dimensional connected porous double network structure,its swelling is 9.16,its maximum compressive yield stress is 0.11-0.28 m Pa,its water contact angle with the surface of polypropylene patch is 13.8°±1.6°,and it has good injectability and cytocompatibility.VEGF in XG/TPEG hydrogels can be slowly released up to 72–120hours.New granulation thickness in XG/TPEG group was 1.65 times higher than in polypropylene mesh group（P<0.05）;the thickness of granulation tissue in the drug-loaded hydrogel group was 1.98 times higher than that in the control group（P<0.01）.There was a significant difference in collagen volume fraction between the hydrogel group（22.1%vs 44.3%,P<0.001）and the drug-loaded hydrogel group（22.1%vs 57.8%,P<0.01）compared with the control group.The number of CD31 expression in neonatal granulation tissue was much higher in the hydrogel and drug-loaded hydrogel groups than in the control group（P<0.01）.The collagen volume fraction was significantly better in the hydrogel group（44.3%vs 22.1%,P<0.001）and drug-loaded hydrogel group（57.8%vs 22.1%,P<0.01）than in the control group.The number of CD31 expression in neonatal granulation tissue was much higher in the hydrogel and drug-loaded hydrogel groups than in the control group（P<0.01）.Compared with the control group,the expression of proinflammatory cytokines IL-6,TNF-αand IL-1 was decreased,and the expression of CD31,α-SMA protein and proinflammatory cytokines IL-4 and IL-10 was significantly increased in the hydrogel group.Conclusion XG/TPEG hydrogel combined stiffness and deformation ability as well as in situ forming propert,which could coat PP mesh to reduce frictions to wound tissues.Moreover,this double-network hydrogel exhibited a denser porous structure that controlled drug release without initial outburst.When testing the hydrogel-coated growth factor-loaded PP mesh on an rat model of OA,it was found that this composite material could reduce inflammation and promote granulation tissue growth.Therefore,it is a new strategy of wound protection of OA and shows potential clinical applications.