Dopamine-inspired Functionalized Polypropylene Materials For Prevention Of Intraperitoneal Adhesion

Polypropylene(PP)mesh is the most commonly used for tissue defect repair material in clinical practice.It has excellent mechanical property,non-immunogenicity,high bioinertia,and no biotoxicity.However,due to its strong foreign body reaction,it often causes serious adhesions between the mesh and the organs,which leads to a series of complications,such as chronic pain,small bowel obstruction,intestinal fistula,infertility,etc.Since the chemical nature of polypropylene is very inert,it is hoped that it can be effectively modified by physical and chemical means to achieve the purpose of preventing abdominal adhesion,and it has become a great challenge.In recent years,inspired by the adhesion of marine mussels,people have found a protein that confers super-adhesive properties on mussels,mussel adhesion protein,in which the derivative of dopamine has received more and more attention.In particular,dopamine has been widely used in the surface modification of different type of polymers.The dopamine-modified material is not only bio-toxic,but has a very high biocompatibility.Therefore,the application of dopamine-based material modification technology in the field of biomedicine is very broad.Although materials modified by dopamine are widely reported,there is no report on the use of dopamine-modified polypropylene mesh materials for the prevention of adhesions after abdominal wall reconstruction.In this paper,the adhesion characteristics of dopamine were fully utilized,different anti-adhesion polypropylene meshes were successfully constructed to optimize the effacicay of adhesion prevention and supply the needs of adhesion prevention under different conditions.We systematically studied the physical and chemical properties and the function of adhesion prevention of different anti-adhesion meshes:(1)By utilizing the self-polymerization characteristics of dopamine in a weak alkaline solution,a stable polydopamine layer was formed on the surface of polypropylene mesh,and then reacted with the side chain residues of–NH₂ of chitosan.The polydopamine/chitosan-coating was formed on PP mesh surface by Michael addition or Schiff's Base reaction between chitosan and polydopamine.The anti-adhesion polypropylene mesh based on dopamine/chitosan was obtained.The physicochemical properties of the meshes were then characterized by ATR-FTIR,FE-SEM,and XPS.The results indicate that polydopamine/chitosan ad-layer can effectively and stably grafted onto the surface of polypropylene.The results of in vitro experiments indicated that the mesh had good biocompatibility and anti-cell adhesion properties.Finally,the in vivo anti-adhesion test was carried out in the rat abdominal wall defect model.The results show that the anti-adhesion mesh has a good anti-adhesion properties and histocompatibility.(2)In order to overcome the shortcoming of chitosan in application,and obtain better adhesion efficacy,the dopamine methacrylamide and poly(ethylene glycol)methacrylic acid monomer directly reacted on the surface of polypropylene with free radical polymerization method.The polymer simulated the structure of the mussel adhesion protein and forms a stably PEG-containing comb-like anti-adhesion layer on the surface of the polypropylene.Physical and chemical characterization indicates that the coating distinguish from common physical coatings due to the presence of catechol groups,which are highly effective and stable on the surface of polypropylene.Cell experiments show that due to the presence of ethylene glycol units,the coating can greatly reduce cell adhesion and showing ultra-low biofouling properties.At the same time,the anti-adhesion experiment in vivo also was proved by the animal modal test.(3)We constructed dopamine-functionalized self-fixing,degradable hydrogel/polypropylene combination anti-adhesion mesh,in order to apply in the repair of abdominal wall defects at the complexity and diversity of surgical conditions for adhesion prevention.The precursors of the hydrogel are two aqueous solutions.As a result,the mesh and the organs can be isolated,thereby the adhesion formation was prevented.As a result,the mash and the organs is isolated,thereby preventing the adhesion forming.The"lap-shear"experiment showed that the gel has good tissue fixing properties to prevent the gel displaced after injection.Cell experiments show that the gel has good biocompatibility.At the same time,animal experiments showed that the gel was completely degraded within 14 days.Abdominal wall defect repair experiments also showed that the gel has excellent anti-adhesion properties and histocompatibility.(4)In order to evaluate the feasibility of adhesion prevention of anti-adhesion PP mesh in Laparoscopic technique and to minimize the interspecies difference,we chose the experimental Bama miniature pig as a model,which is closer to human affinity,as a model.Laparoscopic techniques were used to investigate the prevention adhesion property of anti-adhesion mesh after implantation into its intraperitoneum for a long time(10 months).The results indicate that after the anti-adhesion mesh was implanted for a long time,the mesh did not adhere with viscus,as well as integrated with the abdominal wall.Through using immunohistochemical analysis of the mesh implanted site,it was found that the anti-adhesion mesh has low immunostimulation effect on the surrounding tissue,and can effectively reduces the deposition of collagen on the mesh at the same time,thereby fundamentally preventing the abdominal adhesion.