The development of a nanocrystalline apatite reinforced crosslinked hyaluronic acid-tyramine composite as an injectable bone cement

We have developed an injectable bone cement composed of nanocrystalline apatite and crosslinked hyaluronic acid-tyramine conjugates (HA-Tyr). This bone cement was formed via the oxidative coupling of tyramine moieties catalyzed by hydrogen peroxide (H₂O₂) and horseradish peroxidise (HRP). The bone cement set within 60 s after H₂O₂ and HRP were added to the apatite/HA-Tyr pastes. The mechanical strength of the apatite/HA-Tyr cement was tuned by varying the apatite loading and H₂O₂ concentration. This rapid enzyme-mediated setting of our bone cement results in minimal heat release (ΔH = -11.39 J/g) as compared to conventional bone cements. The crystalline phase and crystallite size (20 nm) of the apatitic phase in our bone cement matched that of trabecular bone. The storage modulus (G′), yield stress (σ_y), and compressive stiffness (E_c) of our bone cement prepared with different apatite loadings and H₂O₂ concentrations were measured, and optimized at G′ = 40 MPa, σ_y = 0.308 MPa and E_c = 2.270 MPa when the cement was formed with 0.4 g/ml of apatite, 0.61 units/ml of HRP and 6.8 mm of H₂O₂. Our biocompatible bone cement also successfully healed small bone and joint defects in mice within 8 weeks.