Apatite-forming ability of polyglutamic acid hydrogels in a body-simulating environment

Artificial joints such as hip joint and knee joint have been popularly used for replacement ofdamaged joints. To achieve a successful outcome offixation of the joints, surrounding bone tissues should have sufficient bone density. However bone density of elderly patients is generally lower than that ofhealthy people due to diseases such as osteoporosis. This also makes it difficult to tightly fix the artificial joints to the bone. Therefore recovery of the bone density is the important factor that governs success on the implantation ofthe artificial joints. As a treatment to increase bone density ofthe patients, injectable bioactive filler with bone-bonding ability, Le. osteconductivity, can be an attractive candidate, since the osteoporosis can be recovered with minimal invasion. Such a filler material should have not only osteoconductive property but also bioresorbability after implantation in the bone tissue. It is known that osteoconduction on bioactive _ materials is achieved by formation of biologically active hydroxyapatite (so-called bone-like apatite) layer on their surfaces through chemical reaction with surrounding body fluid. Heterogeneous nucleation of the hydroxyapatite is triggered by a catalytic effect of specific functional groups on the material surfaces. In addition, release of Ca2+ ions into the surrounding body fluids allows to enhance the apatite nucleation by increasing degree of supersaturation with respect to the apatite. In this study, we attempted to develop injectable bioactive filler started from polyglutamic acid (pGA) through chemical cross-linkage, since PGA is abundant in carboxyl group that is effective for inducing the apatite nucleation in body environments. The cross-linkage lead PGA hydrogel, whereas PGA without cross-linkage easily dissolved in aqueous media. The potential of the bone-like apatite formation was examined on the PGA gels due to exposure to a simulated body fluid (SBF) proposed by Kokubo and his colleagues. After soaking in SBF for 7 days, trace amounts of particles were formed on the PGA gel, but were not identified to bone-like apatite with X-ray diffraction. Formation of bone-like apatite layer could be detected with X-ray diffraction on the PGAgels treated with CaCh aqueous solution of 0.01 mol"dm-3 or more, followed by soaking in SBF for 7 days. The rate ofapatite formation increases with increasing concentration ofthe CaCh in the prior treatment. These results indicate that chemically cross-linked PGA gel has a potential to induce the heterogeneous nucleation ofhydroxyapatite in body environment, and that the potential would be remarkably enhanced by prior treatment ofthe gel with CaCh aqueous solution