Biological Activity And Biomechanical Determination Of Mineralized Collagen - Binding Strontium Composite Bone Cement

Background:In arthroplasty, through forming stable mechanical binding with the surrounding bone tissues, bone cements can achieve a relatively long-term stability. However, over time, the bone-bone cement interface can become loose. Therefore researching and developing bioactive bone cement has significant clinical implications. Our prior studies have found that adding 15 percent of mineralized collagen (Mineralized collagen, MC) in Porymethylmethacrylate can enhance the bioactivity of the bone cement.Objective:To further enhance the bioactivity,We created a kind of new bioactive bone cement (SR-MC-PMMA) through mixing SrHPO4 and mineralized collagen (MC) to Polymethylmethacrylate (PMMA), and investigated its biological mechanics and bone tissue compatibilityMethods:We added different ratios of SrHPO4(1%、2%、5%、10%)to PMMA which contained 15% MC, and investigated their biotogical mechanic functions, including setting time, compressive strength, flexural strength, following the national standard ISO 5833 about MMA bone cement. Under the ratios of SrHPO4, MC vs PMMA being 5%,15% respectively, we prepared the SR-MC-PMMA and chose the mouse L-929 fibroblast recommended by the GB/T 16886.5-2013/ISO 10993-5:1999 for testing. We determined the cytotoxicity in the eluents from SR-MC-PMMA(5%SrHPO4), MC-PMMA, and C-PMMA. Using the grading standard according to national standard GB/T 16886-2003/ISO 10993-5:1999, we investigated the in vitro cytotoxicity of the bioactive bone cement.Under aseptic condition, we embedded the SR-MC-PMMA into New Zealand rabbits’ femoral condyles and retrieved the femoral condyles at four weeks, eight weeks, and 12 weeks after the embedding operations. The specimens were examined using Micro-CT and pathological section after fixation by the fixative liquid. We analyzed the bone CT density and bone compatibility in relevant regions and measured area ratio of bone tissue/bone cement.Result:Our new PMMA, which contained 15% mineralized collagen and 5% SrHPO4,demonstrated a compressive strength of 73.77±6.33MPa and a compression modulus of 1.74±0.11GPa, which make it consistent with national standard (ISO 5833/ASTM F451) requirement on compressive strength of MMA being no less than 70MPa. The solidification characteristic showed performance of PMMA containing 5% SrHP04 did not change significantly over time and had excellent performance. Multiple tests including in vitro cytotoxicity, acute systemic toxicity, chronic liver/kidney toxicity showed that this bfoactive bone cement was safe according to GB/T 16886/ISO 10993.In the pathological tissue sections of rabbit femurs observed at weeks 4,8, and 12 after the embedding operations, the SR-MC-PMMA group exhibited good bone tissue ingrowth. At week 12, on area ratio of bone issue/bone cement (bone tissue ingrowth ratio), the SR-MC-PMMA group (15.99 ± 0.41%) was significantly higher than the MC-PMMA group (9.85 ± 0.72%). In the PMMA group, no significant difference in bone tissue ingrowth ratio was observed along weeks 4,8, and 12. Both in the MC-PMMA group and the SR-MC-PMMA group, new bone tissue ingrowth were statistically significantly different at weeks 8 and 12 comparing to their respective week 4 observations.Conclusion:Our new PMMA, which contains 15% mineralized collagen and 5% SrHPO4, demonstrated compressive strength, flexural strength, and solidification mechanics consistent with the national biological material standard (ISO 5833) and had shown excellent performance. The investigation of SR-MC-PMMA, which included in vitro cytotoxicity, acute systemic toxicity, chronic liver and kidney toxicity, showed its bioiogical safety. Compared to C-PMMA and MC-PMMA, SR-MC-PMMA had demonstrated greater bone ingrowth and excellent biological activity.