The central idea of this project is that solid state magnetic resonance (SSMR) imaging and spectroscopy can provide unique solutions to problems related to the chemistry of biomineralization. In this continuation of the development of SSMR methodology for bone mineral characterization, in vivo and high resolution SSMR techniques are applied to study the remodeling of synthetic calcium phosphate biomaterials in vivo, and to elucidate the structural chemical properties of bone mineral crystals. The work focused on measurements that can be made in no other way with existing technology.
In Specific Aim 1, the conversion of a non-proprietary beta-tricalcium phosphate (TCP) implant into the host bone in a rabbit bone defect model is follow with in vivo and high resolution SSMR. Although much effort has been expended in the study of this and similar increasingly used calcium phosphate based materials, these materials have rarely been studied by solid state MR, and never in vivo by this method. Forty-five rabbits will be implanted, and the time course of the remodeling of the implant material will be characterized by in vivo SSMR imaging, and by high field high resolution cross polarization/magic angle spinning (CP/MAS) spectroscopy, chemical analysis and histomorphometry on harvested specimens. This study is expected to elucidate details of the chemistry of the remodeling process that have so far remained obscure.
In Specific Aim 2, specialized CP/MAS and other solid state MR techniques in conjunction with computer modeling are applied to characterize bone mineral crystals in order to develop detailed model of the structural chemistry of the crystal interior as well as the surface. Specimens of trabecular bone from normal and ovariectomized rats, treated and not treated with alendronate, a typical diphosphonate anti-resorptive pharmaceutical of rapidly increasing importance in the treatment of osteoporosis, will be analyzed. Because the action of diphosphonates includes physicochemical effects involving binding to bone mineral crystals, enhanced understanding of the structural chemistry of bone mineral crystals and their diphosphonate binding properties will be important in the design of improved anti- resorptive drugs.
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