Body Heat-Activated Polymer-Mineral Composites for Vertebral Body FracturesPublic
Polymer and polymer/ceramic composites known as bone cements are commonly used in musculoskeletal reconstructive surgeries where bone tissue fixation, reinforcement, or void filling may be needed. Polymethylmethacrylate, PMMA, was the initial (and currently only) FDA-approved bone cement for bone-void filling applications yet faces many inherent material-based challenges that impacts its use and success as a viable material in biomedical applications. This work presents an alternate bone cement design for bone-void filling applications composed of citrate-based biomaterials (CBBs), ceramic, and a thermoresponsive initiator to address the shortcomings of clinically used bone cements. Vertebral compression fractures due to osteoporosis require materials that are easy to handle, quickly fill and set within a bone cavity, provide similar mechanics to the surrounding bone, and effectively integrate within the bone structure, though these materials are currently based on the non-degradagle, mechanically stiff 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. Thermoresponsive polymers such as CBBs have shown potential use in orthopedic applications as pre-molded biomaterials. However, their ability to mimic the quick-setting ability of bone cements has not been explored. The objective of this research was to investigate whether CBBs could be functionalized to mimic bone cement polymerization mechanics via methacrylation of poly(1,8-octanediol co-citrate) (mPOC) and introduction of an azo-based radical initiator. We show that the addition of a ceramic component (hydroxyapatite, HA) and a thermoresponsive component (2,2’-Azobis(4-methoxy-2,4-dimethylvaleronitrile, V70) produces a quick-setting, tunable polymer composite suitable for bone void filling applications. mPOC-60HA was the most viable composite in vitro and in vivo, producing results on par with clinically used PMMA. The HA provided a modular platform that tailors to specific bone mechanics. The results support the use of the thermoresponsive mPOC for bone cement applications over clinically used PMMA.
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