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 (H(2)O(2)) and horseradish peroxidase (HRP). The bone cement set within 60s after H(2)O(2) 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 H(2)O(2) concentration. This rapid enzyme-mediated setting of our bone cement results in minimal heat release (DeltaH=-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 (sigma(y)), and compressive stiffness (E(c)) of our bone cement prepared with different apatite loadings and H(2)O(2) concentrations were measured, and optimized at G'=40 MPa, sigma(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 H(2)O(2). Our biocompatible bone cement also successfully healed small bone and joint defects in mice within 8 weeks.