Improving bioactivity and the anti-bacterial properties of two-solution bone cement containing cross-linked polymethylmethacrylate (PMMA) nanospheres (eta-TSBC)

The high viscosity standard two-solution bone cements (STSBC) developed in our laboratory exhibits several advantages over other commercial powder-liquid cement formulations. However, the high monomer concentration, viscosity, and exothermal temperature are considered a major limitation to the use of this material. Modified two-solution cements containing cross-linked polymethylmethacrylate (PMMA) nanospheres (η-TSBC), as part of the polymer phase, were fabricated as the first step for optimization of cement viscosity for application of the material in the treatment of vertebral compression fractures using vertebroplasty (VP) and kyphoplasty (KP). The η-TSBC exhibited reduced viscosity, lower polymerization exotherm, and residual monomer in comparison to STSBC. Nevertheless, the ηTSBC lacks bioactivity and has no biologic potential to remodel or integrate into the surrounding bone. Also, addition of radiopacifiers such as barium sulfate and zirconium dioxide is required for fluoroscopy guided procedures and is known to be detrimental to the cement mechanical and bioactive properties. In this sense, η-TSBCs containing strontium-substituted hydroxyapatite (SrHA) microspheres have been developed in this study as a step towards improving bioactivity of these cement formulations. Hydroxyapatite (HA) is a natural bone mineral component and strontium is known to stimulate bone formation and acts as a good contrast agent. In addition to this, recent studies (1-4) have shown that the antibacterial property of hydroxyapatite nanoparticles improved after partial or complete substitution of calcium with strontium ions. The goal of addition of SrHA microspheres into the η-TSBC formulation is to improve bioactivity by allowing apatite formation on the cement surface that would in turn help making chemical bonds with the HA in the surrounding bone, and also to impart radiopacity and antibacterial properties without the need to incorporate any additional radio contrast or antibiotic filler material. The addition of SrHA microspheres at different concentrations resulted in improving the apatite forming ability of η-TSBCs. The antibacterial properties of η-TSBC containing SrHA microspheres were investigated in vitro by culturing Escherichia coli (E.coli) K12/pRSH103 biofilm which resulted in reduced biofilm growth on the cement surfaces with increasing SrHA concentration, indicating capability of bacterial inhibition. The addition of SrHA microspheres resulted in a reduction of mechanical properties in comparison to η-TSBC, bringing these values closer to the human cancellous bone. However, the mechanical properties were similar to the ηTSBC containing 20% wt/vol ZrO2 as a radiopacifier, indicating no further detrimental effect of the SrHA addition on the η-TSBC properties while replacing ZrO2 in order to impart radiopacity and improve bioactivity. These cements were observed to require further optimization to improve interfacial bonding of the SrHA microspheres to the cement matrix for enhancement of mechanical properties of the material. In summary, η-TSBCs containing SrHA microspheres were developed exhibiting a combination of attractive properties and potential for additional modification that will prolong the life and performance of arthroplasties and vertebral