Preparation Of Bi-layer Degradable Nanofiber Membrane And Its Potential Application In Anti-adhesion Barrier

Abdominal adhesion is one of the most common complications after peritoneal trauma,which is manifested as pathological fibrous tissue adhesion between organs and abdominal wall after abdominal surgery,involving nearby normal organs,which has been an important problem in the field of surgery for a long time.According to statistics,the probability of postoperative abdominal adhesion can reach 90%,resulting in severe consequences such as intestinal obstruction,infertility,abdominal pain and pelvic pain,which not only threaten the postoperative health of patients but also cause a heavy economic burden.The most basic method to prevent adhesions is to improve surgical skills,but its effect is limited,can not completely avoid adhesions.In addition,the prevention of adhesions can be prevented by using drugs to reduce the inflammatory reaction of postoperative wounds and thus reduce the occurrence of adhesions.However,some drugs have problems such as affecting wound healing and unstable action time,weakening the anti-adhesions effect in later stage.The mechanism of physical barrier is to isolate the surgical wound and other human tissues at the stage of adhesion formation,so as to prevent the formation of abdominal adhesion.Represented by absorbable anti-adhesion film,physical barrier has become the most widely used anti-adhesion method at present.However,the existing commercial anti-adhesion film is mostly non-porous structure,unable to transport nutrients and exchange waste liquid generated at the wound,which will cause wound hysteresis healing while preventing adhesion.At the same time,many problems,such as high brittleness,poor operability,too long degradation time,degradation products will stimulate the body to induce harm,make there is no ideal antiadhesion material can completely prevent adhesion.The research and development of new antiadhesion film materials is still the focus of biomedical and medical textile research.In view of the deficiency of the existing anti-adhesion film,a double-layer nanofiber film is designed in this project,which is based on Polyglycolic acid(PGA)and Polylactic acid(PLA),and Phosphatidylcholine(PC)is added into it.PC as a functional reagent to inhibit the proliferation of fibroblast adhesion.Considering that the degradation products of PGA and PLA are acidic and easy to cause inflammation,a double layer fiber membrane was prepared by combining PGA/PLA/PC fiber membrane with a photocrosslinked Gelatin(GelMA)modified by anhydride of methacrylate.The double-layer anti-adhesion film material not only has the unique structural advantages of soft self-supporting,lightweight porous and good mechanical strength of nanofiber film,but also has the lubrication characteristics of hydrogel material.Finally,it can achieve multiple functions of anti-cell adhesion,lubrication and improving degradation environment.The main research contents and results are as follows:(1)Nanofiber membranes with different ratios of PGA/ PLA,PGA/ PLGA were prepared by electrostatic spinning method.The effects of composition on the morphology,mechanical properties and degradation properties of the fiber membranes were investigated.Finally,the fiber membranes with a mass ratio of PGA to PLA of 5:5 were selected as the substrate.(2)Based on the polymer mass ratio explored above,functional reagent PC with different mass concentrations was added into the spinning stock solution to prepare nano-fiber membranes with good morphology by electrostatic spinning method.The results showed that the higher the concentration of PC was added,the stronger the anti-fibroblast adhesion and proliferation ability of the fiber membrane was.Finally,the fiber membrane with 10% PC mass concentration was selected for subsequent experiments.(3)GelMA was prepared by the reaction of gelatin and methacrylate anhydride,and the spinning parameters of nano-fibers with good morphology were investigated by using electrostatic spinning technology.Finally,it was determined that smooth and uniform nanofibers without beads could be formed when 3.5 m L/h and 15 k V were used as spinning parameters.(4)Finally,PGA/PLA/PC and GelMA were prepared by interlayer co-spinning.The study showed that GelMA component could effectively alleviate the acidic environment caused by the degradation of PGA and PLA,and the preparation process had no effect on the anti-cell adhesion proliferation of PGA/PLA/PC layer.At the same time,the GelMA layer makes the two-layer fiber film have good lubrication.