Polyethylene Glycol Crosslinked Starch Compound Gel Loaded Rifampin Sustained Release Coating Experimental Study

Hip tuberculosis is one of the most difficult diseases in Department of orthopedics.One of the main reasons is that antituberculosis drugs are difficult to achieve effective bactericidal concentration and drug-resistant tuberculosis in the lesions.Late treatment of tuberculosis of the hip joint can cause loss of joint function and deformity.Arthroplasty has been widely used in the treatment of advanced hip tuberculosis.Arthroplasty for one-stage joint arthroplasty has been widely recognized this year,but there are still risks and concerns of postoperative recurrence.Therefore,improving the concentration of drug in the focus is a very good bottleneck to solve this problem.The sustained release drug coating on the surface of the prosthesis has become a hot spot in preventing the recurrence of prosthesis replacement.Titanium alloys are commonly used in medical prosthetic materials.In this study,Ti-PPCR coating was prepared on the surface of titanium alloy by polymer chemical reaction.1.Preparation of PPCR composite gel coating on the surface of titanium alloyProduction of crosslinked starch(crosslinked starches,CS);by polymerization in the artificial hip joint of titanium alloy(titanium alloy,Ti alloy)material is formed on the surface of polydopamine(poly dopamine,PDA)chemical film;Li Fuping(rifampicin,RFP)powder loaded into cross-linked starch and polyethylene glycol four(polyethylene glycol,arm PEG)in forming the water gel by Michael addition reaction of PAD and PEG-CS-RFP firmly with formation of PAD-PEG-CS-RFP coating.2.The microstructures of the experimental materials were observed under the scanning electron microscopeThe surface profiles of Ti,Ti-PDA and Ti-PPCR were observed under scanning electron microscope(SEM).Their microscopic characteristics were described,and the mechanism of drug release was deduced based on the results of drug release.Three kinds of materials were characterized by scanning electron microscopy.3,bacteriostasis experiment of Mycobacterium tuberculosis in vitroThey were coated with single side Ti-PPCR coating and Ti-PAD-PEG-CS,respectively,and placed in standard Roche medium of H37 Rv,and incubating in 37 temperature incubator for 20 days to observe the formation of antibacterial ring.In the same way,Ti,Ti-PAD-PEG-CS and Ti-PPCR were put into the same Roche medium to observe the bacteriostasis.4.The experiment of drug release in vitro and in vivoIn vitro: take the Ti-PPCR material into 20 ml simulated body fluid(SBF)and then put it in a 37 degree centigrade thermostat.The release rate and cumulative release rate of 12 h,1D,2D,3D,4D,5D,6D,7d,8D and 9D time points were measured by HPLC.In vivo: 20 New Zealand rabbits,2 sterilized Ti-PPCR(thickness 0.4mm,diameter 1.1 cm)into the right femoral condyle,animal model in vivo drug release,postoperative 5D,10 d,15d,20 d,RFP,drug concentration was detected by HPLC in venous blood,bone implant material around the 0.5cm group the fabric and muscle tissue.5.Evaluation of biocompatibility of tissues in vivo24 New Zealand rabbits were randomly divided into experimental group and control group with 12 rats in each group,the experimental group was implanted with Ti-PPCR(about 1.26 mm in thickness,diameter of 1.1 cm),the control group was implanted with sterilized blank titanium alloy slice(thickness 1mm,diameter 1.1cm),complete the animal model after operation in 1W,2W,3W,4W after 3,remove the complete femoral condyle,hard tissue slicing machine cut out with the thickness of 200 um titanium alloy by slicing,grinding machine grinding disc to 30 um,HE stain.The inflammatory response of the bone tissue around the material was observed under an optical microscope.The results show that the PPCR composite gel coating can be firmly combined with the titanium alloy experimental materials.Under scanning electron microscope,the surface of the coating is smooth,and the longitudinal section structure is void.Bacteriostasis rings around Ti-PPCR(experimental group)in neutral Roche medium.In the simulated body fluid,the release rate of RFP in the former 3D was faster,and the cumulative release amount of Ti-PPCR in the simulated body fluid accounted for 63.2% of the total dose.Then the release tended to be smooth,the total release rate was 79.2%,and the total release time was 9D.The concentration of drug in bone tissue and muscle tissue increased rapidly,reached the peak on the fifth day,then decreased gently,the total release period could reach 20 days and 10 days respectively,and all of them were above the minimum bactericidal concentration,and rifampicin was not detected in venous blood.Histological examination showed that there was a small amount of neutrophils and lymphocytes infiltration in the experimental group and the control group in the first 2 weeks of histology.The experimental group was less than that in the control group.The inflammatory cells in third weeks and fourth weeks were less than those in the first two weeks.The conclusions are as follows: 1.the Ti-PPCR anti tuberculosis and sustained release gel coating was successfully prepared on the surface of titanium alloy through the principle of polymer chemical reaction.The 2.Ti-PPCR anti tuberculosis and sustained release gel coating has good drug release kinetics and bacteriostasis.3.Ti-PPCR anti tuberculosis and sustained release gel coating has good histocompatibility.