Antibacterial Peptide-based PH-responsive Antibacterial Hydrogel Vascualr Grafts

Thrombosis and infection are the main reasons that restrict the clinical applications of permanent transplantation of small diameter vascular grafts.Many studies have continued to focus on improving the blood compatibility of vascular graft materials,including anticoagulation,antithrombotic properties,low hemolysis rate,and platelet resistance,but less attention has been paid to the antibacterial properties of vascular grafts.With the increase of clinical application of vascular arteriovenous graft,the problem of infection has become increasingly prominent.The ideal small-diameter vascular graft should have uniform and controllable diameter and structural stability,favorable mechanical properties matching natural blood vessels,satisfactory cell and blood compatibility.Moreover,anti-infection ability is a key point for applications as vascular access.This study is based on the performance of hydrogel vascular grafts,combined with surface modification technology,in order to obtain an antibacterial hydrogel vascular graft material with bacterial microenvironment response,and provide certain clinical aspects for small-diameter vascular grafts in hemodialysis and other clinical aspects.The main experimental results and conclusions of this study are as follows:（1）PVA/PAAm（5:8）hydrogel material was successfully prepared,and a small-diameter vascular graft material with an inner diameter of 3 mm was prepared by combining a polyester monofilament braided strut.The vascular graft material has a smooth surface,a uniform and stable pipe diameter structure,a uniform internal microporous structure,a volume swelling rate close to 100%,and shape changes are not easy to occur.The elastic modulus is 0.49±0.01 MPa,which falls into that of natural blood vessels.（2）The antibacterial modification of the hydrogel vascular graft material was carried out.First,a polymer brush structure is grafted on the surface and melittin MLT is fixed to give the material antibacterial ability.Then it covalently binds the shielding group 2,3dimethylmaleic anhydride DMMA with the antibacterial surface to achieve a pHresponsive antibacterial strategy and maintain good biocompatibility of the material.The chemical composition analysis proves the successful modifications of each step.The DMMA dissociation test confirmed the pH responsiveness of the modified antibacterial hydrogel material.（3）The antibacterial properties of the modified antibacterial hydrogel vascular graft materials were tested under different conditions.The results show that under normal physiological conditions,the surface of the modified antibacterial hydrogel with DMMA can shield the biological toxicity of MLT,and has no bactericidal ability.In the environment of bacterial metabolism,the surface of the modified hydrogel undergoes a charge reversal due to changes in pH,and the stimulus response removes the DMMA shielding ability and exposes the MLT bactericidal ability.（4）In vitro cytotoxicity and blood compatibility experiments were then conducted on the modified antibacterial hydrogel vascular graft materials.The results show that the modified hydrogel material is not cytotoxic.The hemolysis rate is 0.16%,which shows it is a non-hemolytic material.The coagulation index BIC<0.3,suggesting the material has good anticoagulation performance.There was no obvious platelet adhesion and red blood cell lysis on the surface of the material.The modified hydrogel material has favorable cell and blood compatibility,and is an ideal biomaterial for the preparation of vascular grafts.In summary,the pH-responsive antibacterial hydrogel vascular graft material prepared in this study has a stable structure,excellent mechanical properties,has the ability to respond to pH changes caused by changes in the microenvironment of bacterial metabolism,and can effectively kill bacteria.At the same time,it has good cell compatibility.The hydrogel vascular graft is not hemolytic,has excellent anticoagulant performance,and is not easy to adhere platelets and red blood cells.This study lays the foundation for the clinical application of antibacterial hydrogel vascular grafts.