Research On Preparation And Properties Of Oxidized Regenerated Cellulose Medical Sutures

In recent years,Oxidized Regenerated Cellulose(ORC)has become a research hotspot due to its excellent biocompatibility,long-acting antibacterial,immune stimulation,promotion of wound healing and virus resistance and other physiological functions.Its representative product is ORC hemostatic gauze.However,ORC hemostatic gauze has the rapid degradation and poor mechanical properties caused by its high carboxyl content,which limited its further application in the field of medical sutures.As a kind of medical suture with excellent properties,it should possess good mechanical properties and controllable degradation.In this thesis,quantum chemical calculation method and molecular dynamics were used to study the change of transition state energy in the selective oxidation cellulose of the different oxidation system,the change of transition state energy and solubility parameter performance in the degradation process of ORC-based materials.Meanwhile,we also discussed the degradation mechanism of ORC-based materials.Finally,the basic application of ORC as medical suture was further studied.The transition state energies of different oxidation systems at C2 and C6 positions of cellulose were analyzed by quantum chemical calculation method.The simulation results showed that TEMPO and HNO3 had good selective oxidation on C6 site of cellulose.However,the oxidation process of cellulose via the HNO3 are too violent and rapid to cause the obtained productsto be over-oxidized.Therefore,mild TEMPO oxidation system was selected as the oxidation system for subsequent experiments.In addition,ORC prepared by TEMPO oxidation system had controllable mechanical properties and carboxyl content.Meanwhile,N,Ocarboxymethyl chitosan(N,O-CMC)/oxychondroitin sulfate(OCS)composite hydrogel and GelMA/EPL electrospun nanofibers were used to modify the surface of ORC,and then the ORC/N,O-CMC/OCS and ORC/GelMA/EPL materials with excellent properties were obtained.In order to clarify the degradation performance of ORC and modified ORC materials in solution,the in vitro degradation rates of ORC,ORC/N,O-CMC/OCS and ORC/GelMA/EPL were tested.After 28 days of immersion in PBS solution,the in vitro degradation rates of ORC,ORC/N,O-CMC/OCS and ORC/GelMA/EPL was 22.2%、33%and 27.34%,respectively.The degradation mechanism of ORC is mainly attributed to the process of decarboxylation degradation.The degradation mechanism of ORC/N,O-CMC/OCS is mainly attributed to the formation of ORC-Na during the reaction between N,O-CMC/OCS hydrogels and ORC,which leads to the enhancement of ORC’s water solubility.Meanwhile,the swelling of N,O-CMC/OCS hydrogels also promotes the dissolution of ORC surface during in vitro degradation.The degradation mechanism of ORC/GelMA/EPL is mainly attributed to the fact that the nanofiber membrane can effectively cover ORC at the initial stage of degradation,avoiding the erosion of ORC by a large amount of liquid.With the hygroscopic swelling of the nanofiber membrane,the fiber porosity increases,promoting the contact between ORC material and external water.Then ORC begins to partially degrade.Meanwhile,the molecular dynamics simulation results showed that the solubility parameters of ORC,ORC/N,O-CMC/OCS and ORC/GelMA/EPL materials decreased gradually during the degradation process,which further illustrated the influence of different modification methods on the solubility of ORC materials in PBS solution.Compared to N,O-CMC/OCS hydrogel mateials,the GelMA nanofibers can effectively cover ORC materials,which can effectively maintain the mechanical stability of ORC in the degradation process.The medical suture formed by ORC,ORC/N,O-CMC/OC S and ORC/GelMA/EPL have stable diameter and excellent mechanical properties(good knot tensile),which can meet the suture requirements for epithelium,muscle and other general tissues.The toxicity of medical suture materials formed by ORC,ORC/N,O-CMC/OCS and ORC/GelMA/EPL is relatively lower,and the grade of intradermal stimulation reaction is extremely mild without obvious systemic toxicity.The hemolysis rate of ORC,ORC/N,O-CMC/OCS and ORC/GelMA/EPL is lower than 2%,and those suture materials do not cause obvious erythrocyte deposition and aggregation.It indicates that the material has good biosafety and blood compatibility,and meets the requirements of cytotoxicity and biological evaluation standards of biomedical materials.Compared with ORC and ORC/N,O-CMC/OCS sutures,ORC/GelMA/EPL sutures showed stronger antibacterial effect.In conclusion,this thesis uses molecular technology to simulate the change of transition state energy in the reaction process of ORC and ORC/N,O-CMC/OCS and ORC/GelMA/EPL materials,and conducts preliminary molecular simulation for the degradation mechanism of the three materials in vitro.The basic physical and chemical properties,biological safety and effectiveness of medical sutures prepared by the three materials were evaluated,which provided basic theoretical basis for clinical application of ORC based medical sutures in the future.