Synthesis and characterization of self-curing hydrophilic bone cements for protein delivery.

Abstract

New formulations of acrylic bone cements for bone defect reparation, based on self-hardening methyl methacrylate (MMA)/methacrylic acid (MAA), with a high capacity for protein delivery, have been developed. The self-curing formulations were prepared by partial substitution of solid phase PMMA microparticles by newly obtained PMAA microspheres. The PMAA microspheres were prepared by inverse suspension polymerization of their monomer and were cross-linked with N,N'-methylene-bis-acrylamide (MBA) (10-15 wt %) to produce stable systems in contact with aqueous media. PMAA microspheres were loaded with hydrolyzed collagen (HC) as a model protein to simulate bone morphogenetic protein delivery useful for hard tissue reconstruction. Solid phase PMMA microparticles in the formulation were partially substituted by new PMAA-HC microspheres and were characterized to determine viability as an acrylic bone cement in minimally invasive surgery. The incorporation of PMAA-HC microspheres decreased peak temperature by 20°C, which minimized thermal necrotic risk after implantation. Mechanical compression tests revealed a behavior, under dry conditions, close to ISO 5833 standard requirements. However, a drastic drop in mechanical strength, ∼64%, was obtained after 15 days of immersion in simulated physiological conditions (37°C and pH 7.4) and was attributed to water absorption and a subsequent plasticizing effect. The increase in water uptake and retention enhanced the capability for controlled protein delivery. Finally, the biocompatibility of the cements was determined; some toxicity of the material during the first hours of culture incubation was observed. Later, toxicity was observed to decrease due to nonreacted monomer leaching, which ensured the low toxicity of the already polymerized phase.