Surface Modification Of Polyurethane Implants And Their Mechanisms For Resisting Foreign Body Reactions

Polyurethane(PU)materials are widely used in artificial blood vessels,artificial heart valves and prosthetic materials.However,the hydrophobic nature of these polyurethane implants often causes blood cells adhesion and thrombosis during in vivo application.Moreover,polyurethane implants may cause foreign body reaction(FBR),resulting in massive collagen deposition and tissue fibrosis around the implant,and finally leads to implant failure.To address the problems of blood cells adhesion and FBR caused by the polyurethane implants,we immobilize bioactive molecules such as natural polysaccharides and proteins with anti-adhesive and immunomodulatory functions onto the surface of polyurethane implants,and investigate their underlying mechanisms of action.Natural polysaccharides are a class of biologically active macromolecules.Dextran is widely used for surface functionalization and modification of biomedical materials because of its good biocompatibility and surface anti-fouling and anti-coagulation functions.Since dextran lacks active functional groups,modification of dextran to introduce active functional groups is usually required.In Chapter 2,oxidized dextran(Dex-CHO)is immobilized modified on the surface of polyurethane film,and the anti-adhesive properties of the modified coating and its immunomodulatory function on macrophages are also investigated.The experimental results showed that the water contact angle on the surface of the polyurethane material decreases from 93.4° to 68.6° after the modification of oxidized dextran,and the adhesion of red blood cells and platelets on the surface of the material could be effectively reduced.However,compared with unmodified polyurethane,the presence of abundant aldehyde functional groups leads to an increase in the expression of tumor necrosis factor(TNF-α)from 1.0 ng/mL to 11.4ng/mL,showing an M1 phenotype polarization of macrophages and causes a pro-inflammatory microenvironment around the implant.This pro-inflammatory phenotype of macrophages is unfavorable for the in vivo application of polyurethane implants and may cause FBR after implantation.To address the problem of FBR triggered by polyurethane implants,in Chapter 3 of this thesis,the surface of polyurethane film was modified with carboxymethyl dextran(CMD)and a bioactive protein,human chorionic gonadotropin(hCG).The experimental results showed that the CMD and hCG-modified polyurethane(PU-hCG)film shows good biocompatibility and antifouling properties against red blood cells and platelets.In vitro cellular experiments showed that PU-hCG is able to reduce the expression of macrophage inflammatory factor TNF-α from1.0 ng/mL to 0.1 ng/mL.Meanwhile,it increased the expression of macrophage M2 phenotype cytokine IL-10 from 40.9 pg/mL to 127.5pg/mL,suggesting that PU-hCG is able to inhibit the M1 phenotype polarization of macrophages M1 and promote the M2 phenotype polarization.In vivo animal experiments showed that the thickness of the fibrous capsule around the PU-hCG implant was reduced by 61.9%compared with the unmodified polyurethane material,indicating that PUhCG is able to resist foreign body reaction.In this thesis,based on the surface functionalization of polyurethane materials with bioactive molecules such as natural polysaccharides and proteins,a coating with anti-fouling and immunomodulatory functions is successfully fabricated on the surface of polyurethane film,which effectively reduced the adhesion of blood cells and the foreign body reaction.This research reveals the mechanism of the bioactive coatings on the surface of implant materials with anti-blood cells adhesion and anti-foreign body reaction,which may find potential application in the field of producing new polyurethane-based medical implants.