Bioactivity And Antibacterial Activity Of PMMA Bone Cement

Objective:A perfect intergration between the interface of bone cement and bone was essential in designing new bone cement. This research investigated the bone collagen mineralized in vitro(mineralized collagen,MC), a bioactive biomimetic materials, adding to the polymethylmethacrylate (PMMA) bone cement to improve the mechanical properties, biological safety and bone tissue compatibility. This research investigated the compressive strength, elution kinetics, antimicrobial activity of Antibiotic-Impregnated Bone Cement (AIBC) that covered the current bacterial spectrum in Prosthetic-Joint Infections (PJI), and the influence of storage on the elution kinetics of AIBC under room temperature with light protection after gamma irradiation sterilization.Methods:The MC in different proportions (0%,5.0%,10.0%,15.0%,20.0%(wt/wt)) were added to the PMMA bone cement to detect the compressive strength and compression modulus. Select the choice proportion that presenting the best mechanical properties to investigate its coagulation properties.15.0%(wt) impregnated MC-PMMA was choose to detect the biosafety in accordance with ISO10993and GB/T16886method. The MC-PMMA embedded into the medial femoral condyle of New Zealand rabbits to exam bone tissue compatibility with Micro-CT and histological examination at4weeks,12weeks and24weeks respectively. The MG63cells co-cultured in vitro with MC-PMMA for7days and14days, to detect the gene expression of osteonectin (SPARC), collagen1(Coll A1), bone sialoprotein (IBSP) and osteocalcin (BGLAP). The antibacterial study was an in vitro experiment.06×12mm cylindrical samples were prepared with Palacos MV adding vancomycin (Vane), gentamicin (Gent), meropenem (Mero) to4different concentration(1.25%,2.50%,5.00%,10.00%(wt/wt) respectively), adding vancomycin+gentamicin (VaGe), vancomycin+meropenem (VaMe) to5.00%(wt/wt) respectively. The elution profiles were measured over28days. Mechanical tests and antibacterial activity were performed to determine whether any significant change occurred following addition of the antibiotics.5.00%of Vanc-, Gent-and Mero-AIBC were stored under room temperature with light protection after gamma irradiation sterilization. The elution profiles were measured after3and6months respectively.Results:15.0%(wt) impregnated MC-PMMA indicated compressive strength of89.30±5.26MPa and compression modulus of1.21±0.12GPa, while little affected compressive strength and solidification. In accordance with ISO10993and GB/T16886standard, MC-PMMA indicated no toxicity in cytotoxicity, blood compatibility test, acute systemic toxicity, chronic liver and kidney toxicity, and local reaction ater implantation experiments. The bone-cement interface crosslinking was significantly improved after implantation in rabbit medial femoral condyle for4,12and24weeks. The bone tissue ingrowth ratios in MC-PMMA group were7.24±4.46%,10.95±6.34%,14.42±9.72%respectively, which were higher than that of C-PMMA group (2.57±1.31%,2.88±1.20%,3.14±1.65%, respectively, p<0.05). The bone affinity indexes in MC-PMMA group were13.10±1.52%,25.63±1.38%,34.96±2.33%respectively, significantly higher than the corresponding C-PMMA group (8.94±1.47%,12.21±1.56%,12.62±1.42%, respectively, p<0.05). After co-cultured of MC-PMMA and MG63cells for7days and14days, the expression of SPARC, Coll A1, IBSP were increased in the MC-PMMA group(p<0.05). But the BGLAP expression levels was depressed in the7th and14th day(p<0.05). The mechanical properties were negatively affected by increasing adding of antibiotics. The compressive strength would drop around70MPa when the concentration of antibiotics reaches10.00%. The elution profiles ofdifferent AIBC with varialbe concentrations were in accordance with power fitting. Increasing antibiotic addition resulted in significantly greater cumulative elution over28days. The elution ratio of Vane-, Mero-, Gent-AIBC within28days was3.74-7.10%,2.23-5.22%,2.43-4.59%respectively. VaMe-AIBC eluted more Vanc and Mero than the control group (7.96%Vs5.25%(p<0.001),2.86%Vs2.70%(p=0.038) respectively), while VaGe-AIBC behaved a reduction in Vane eluting (4.09%Vs5.25%, p0.001) with little change in Gent eluting (4.09%Vs4.08%, p=0.957). No significant change occurred in antimicrobial activity of all the groups of AIBCs. VaGe-AIBC and VaMe-AIBC could cover all the bacterial spectrum in PJI. The elution profiles of5.00%Vanc-, Gent-and Mero-AIBC showed no significant change after storage for3or6months.Conclusion:15.0%(wt) impregnated MC-PMMA significantly lower compressive modulus, while little affected compressive strength and solidification. MC-PMMA bone cement was biologically safe in vitro and in vivo. The bone-cement interface crosslinking was significantly higher in MC-PMMA than C-PMMA after6months implantation in the distal femur of rabbit. Gene expression detected IBSP, SPARC, Coll A1increased in MC-PMMA. MC-PMMA might improve the bioactivity of osteogenesis. Antibiotic content should not exceed5%while using Vanc-, Gent-, Mero-AIBC for PJI. AIBC could release effective concentration of antibiotic within28days. The presence of meropenem broadened the antibacterial spectrum and enhanced the elution of vancomycin, while gentamicin depressed the elution of vancomycin. The storage, with gamma irradiation sterilization, room temperature and light protection, for6months had little effects on the elution kinetics of AIBC.