Azo polymerization of citrate‐based biomaterial‐ceramic composites at physiological temperatures

Vertebral compression fractures due to osteoporosis are commonly treated with bone cements based on the non‐degradable, mechanically stiff poly(methyl methacrylate) (PMMA), which relies on peroxide‐initiated polymerization to quickly set the cement at the cost of high exothermic temperatures. Recently, there has been interest in developing degradable, bone mechanic‐matching alternatives that pursue physiologically induced polymerization to both augment the handling of the material before application and to reduce high localized temperatures that may lead to tissue damage. Herein, we report the development and material characterization of a thermoresponsive, degradable bone cement that utilizes the azo‐based radical initiator 2‐2ʹ‐azobis (4‐methoxy‐2,4‐dimethyl valeronitrile) (V70) and a liquid citrate‐based biomaterial‐ceramic composite of methacrylated poly(1,8 octamethylene citrate) (mPOC) and hydroxyapatite (HA) nanoparticles (mPOC‐HA) that has improved handling and tissue compatibility characteristics. Our results show that: (a) these composites remain liquid until they are exposed to body temperature, which initiates polymerization to form a solid, tough material with desirable, modular compressive strengths comparable to trabecular bone; (b) the addition of HA decreases temperature generation below the threshold that leads to tissue necrosis; and (c) composites remain biocompatible in vitro and in vivo. Development of a bone cement that incorporates the thermal azo‐initiator V70 into a methacrylated citrate‐based polymer‐hydroxyapatite (mPOC‐HA) composite is investigated herein through materials, in vitro, and in vivo testing. Thermal curing is initiated and achieved at body temperature, with the addition of HA augmenting the cellular and biological response.