The Application Of PLGA-PEG-PLGA Thermosensitive Hydrogels In The Prevention Of Postoperative Adhesion And The Treatment Of Osteomyelitis

Postoperative soft tissue adhesion and osteomyelitis have been a major problem for clinicians.In recent years,with the development of biomedical materials,a variety of biomedical materials continue to emerge,providing a solution to these problems.Two amphiphilic block copolymer hydrogels have been widely used in biomedical fields as a good drug controlled release carrier.The temperature-sensitive tri-block copolymer hydrogel has the properties of good biocompatibility and biodegradability,which can effectively prevent postoperative adhesion of soft tissue ? At the same time,the temperature-sensitive tri-block copolymer hydrogel witch is biodegradable is an ideal drug controlled release carrier,it can be used to deliver bactericide to the local infection by way of injection for the treatment of osteomyelitis,and do not need another operation to remove.Silver nanoparticles(AgNPs)witch with low toxicity and broad spectrum of antibacterial properties are widely used and researched as inorganic fungicides,especially for the treatment of drug-resistant bacterial infections.In this study,the temperature-sensitive poly(D,L-lactide-co-glycolide)– poly(ethylene glycol)-poly(D,L-lactide-co-glycolide)(PLGA-PEG-PLGA)tri-block copolymer hydrogels with different molecular weights were prepared and characterized,and the injectable and biodegradable properties were verified,after that hydrogels were applied to the rat model of abdominaladhesion.Furthermore,PLGA-PEG-PLGA tri-block copolymer hydrogel and AgNPs are physical mixed,for the first time,AgNPs/PLGAPEG-PLGA composite hydrogel was prepared and used to treat osteomyelitis caused by drug resistant bacteria,the therapeutic effects were proved to be effective.Specific contents are as follows:1.PLGA-PEG-PLGA tri-block copolymers with different molecular weights were prepared by ring opening polymerization.The copolymer aqueous solution showed a sol-gel phase transition with increasing temperature.The structure and composition of the products were determined by 1H NMR.The sol–gel phase transitions of the PLGA-PEG-PLGA solutions in PBS(PH 7.4)were studied by the vial tilting method.The phase-transition temperatures of polymer with different concentrations were from 27? to 32?,which confirmed by rheology analysis.In addition,the results of in vitro degradation test and cytotoxicity test showed that the hydrogel prepared by this method has a good degradation rate and good biocompatibility.The possibility of its used as a barrier to prevent postoperative adhesion of soft tissue was explored.2.Silver nanoparticles which prepared by reduction of silver nitrate were mixed with the prepared PLGA-PEG-PLGA three block copolymer hydrogel.A new type of AgNPs/PLGA-PEG-PLGA hydrogel was prepared.The properties of AgNPs/PLGA-PEG-PLGA composite hydrogels were characterized.The AgNPs/PLGA-PEG-PLGA composite hydrogel still has a temperature sensitive property,and the sol-gel phase transition occurs with the increase of temperature.Novel hydrogel can be sustained release of silver nanoparticles to play antibacterial properties.In vitro and in vivo biocompatibility experiments showed that the novel AgNPs/PLGA-PEG-PLGA hydrogel has good biocompatibility and nocytotoxicity.The effective of the novel hydrogel in the treatment of osteomyelitis was proved to be good.It is a new type of composite hydrogel with good application prospect.The results of this study show that PLGA-PEG-PLGA tri-block copolymer hydrogel with good biocompatibility is injectable and biodegradable,and it can be used to effectively prevent postoperative adhesion of soft tissue as a barrier.After that,AgNPs/PLGA-PEG-PLGA tri-block copolymer hydrogel was prepared for the first time.The good biocompatibility and antibacterial property of the novel hydrogel were confirmed,which lay a theoretical foundation for its further application in clinical treatment.