Osteoporosis and low bone mass affect more than 50 million people in the US, with vertebral compression fractures as the major source of morbidity and health care costs. For patients with mild or minimal pain, and initially even for patients with severe pain, conservative therapy is usually the first choice. Such treatment including opiates, braces and bedrest have their own risk profile. For patients with severe pain, minimally invasive fluoroscopy-guided procedures, vertebroplasty and kyphoplasty, that involve injection of cement bone into the vertebral body are typically considered to stabilize fractures and provide mobility. Cement leakage is the most common complication of vertebroplasty and kyphoplasty. The high heat of polymerization of the implant cement can cause thermal damage to surrounding tissue, nerves and spinal cord. Additionally, current cements with high modulus (stiffness) can also result in stress to adjacent vertebrae and spinal structure. No current cement formulation simultaneously addresses the issues of high temperature and modulus. In this proposal, we hypothesize that a phase change additive can decrease the peak polymerization temperature of acrylic bone cement to below the cell necrosis temperature while simultaneously decreasing its modulus of elasticity. This idea is based on the scientific premise that a suitable phase change additive, which undergoes endothermic melting during exothermic polymerization of the cement, will absorb sufficient heat to maintain a low peak temperature. As our pilot data shows, a fatty acid based acrylic polymeric additive was able to substantially decrease the peak polymerization temperature while simultaneously decreasing its modulus and provides a pathway to address both these problems.
The Specific Aims are: first, to test the hypothesis that a suitable phase change polymer can decrease the peak polymerization temperature of acrylic bone cement to a temperature below the cell necrosis temperature by formulating the polymer and measuring cement setting temperatures; second, to test the hypothesis that the phase change polymer will decrease the modulus of elasticity of acrylic bone cement by mechanically testing cements of various formulations containing the phase change polymer; third, to compare the cytotoxicity of a control acrylic cement with a cement containing the phase change polymer. Successful completion of this project will provide guidance to develop cement formulations that will not cause thermally induce tissue damage and thereby improve fixation of the cement not just for vertebral augmentation but easily translatable to improve anchoring for joint replacements, dental implants, and fixation in craniomaxillofacial and other trauma applications. It will also allow incorporation of heat sensitive biomolecules, such as bone morphogenetic proteins, growth factors, as well as heat sensitive antibiotics to be incorporated into the cement. Lastly, it will, in the future, allow formulations that could be used for rapid cast formation without burning skin. We therefore believe that this patent protected platform technology has far reaching value for a variety of applications, and serving several unmet clinical needs.
Bone cements meet a clinical need in fixation of fractured spinal cord vertebrae for patients with osteoporosis who have undergone vertebral compression fracture, occurring in 700,000 patients each year in the US. A drawback associated with implantation of bone cements by vertebroplasty or balloon kyphoplasty, is that they can leak into the spinal canal risking thermal damage due to the high heat of polymerization. This proposal aims to provide guidance to develop new bone cements with a significantly low temperature of polymerization to allay any concerns of thermal tissue damage occurring both within the vertebrae as well as in the surrounding tissue in cases of cement leakage.