CALCIUM PHOSPHATE BONE REPAIR MATERIALS

描述（改编自研究者摘要）：磷酸钙 在该研究项目下开发的水泥（CPC）已于年获得FDA批准。 1996年用于人类颅骨缺陷修复应用，从而成为第一个 这类材料可用于临床。虽然CPC被证明 在许多牙科和医疗应用中是非常有用的 材料不能很好地工作，体内研究结果表明，为了 为了达到最佳效果，CPC应具有处理和体内特性， 最适合于特定的临床应用。的目标 建议的研究是阐明水泥凝固反应的机理， 了解影响水泥处理的物理化学因素， 体内特性。提出了四个具体目标。目标1建议， 了解控制四钙水解反应的因素 磷酸盐（TTCP）、α-磷酸三钙（α-TCP）、磷酸二钙 二水合物（DCPD）、无水磷酸二钙（DCPA）和氢氧化钙。 这些磷酸钙盐是不同CPC的主要成分。 形成羟基磷灰石（HA）的一种或多种盐的水解是 负责水泥的硬化。更好地理解 这些盐中每一种的水解反应将提供重要的见解， 影响一些重要水泥性能的因素，包括 转化为HA，形成Ca缺乏或化学计量的HA， 有缺陷的或非化学计量的HA被认为是 更容易被生物吸收目的2提出研究骨水泥的溶解速率 在具有模拟离子组成的脱矿质溶液中的产物， 破骨细胞产生的酸性环境。一个对偶常数合成 在本报告所述期间开发了滴定系统， 磷酸钙生物材料在模拟酸化条件下的溶出速率 生理解决方案主要研究者建议使用此 技术作为预测CPC再吸收率的体外模型， 了解控制溶解速率的因素。目标3：研究 非刚性和可吸收磷酸钙骨水泥的性能。实验 研究了CPC和生物相容性聚合物壳聚糖的复合材料 以形成自硬化、生物可吸收和非刚性的骨移植材料。 这些材料在许多应用中应该是有用的，其中， 植入物可以保持稳定并牢固地附着到骨缺损表面 尽管有缺陷壁的微运动。目标4将研究 可注射预混磷酸钙骨水泥糊剂。预混CPC浆料具有 它们在包装中是稳定的， 输送到缺陷部位，在那里非水液体被水代替 从周围组织中分离出来虽然预混CPC更容易使用， 并且是可注射的，其性质与常规的 CPC。研究了预混复合材料的硬化时间、抗冲刷性和HA转化率， 由CPC粉末和非水液体如甘油组成的糊剂将 被研究。主要研究者还建议确定机械 硬化CPC浆料的性能。

DESCRIPTION (Adapted from the Investigator's Abstract): A calcium phosphate cement (CPC), developed under this research project, was approved by the FDA in 1996 for cranial defects repair applications in humans, thus becoming the first material of its kind to be available for clinical use. While CPCs were shown to be very useful in a number of dental and medical applications for which other materials do not work well, in vivo study results suggest that in order to achieve the best results, CPC should have handling and in vivo properties that are best suited for the particular clinical application. The objectives of the proposed research are to elucidate mechanisms of cement setting reactions and to understand the physicochemical factors that influence cements= handling and in vivo properties. Four specific aims are proposed. Aim 1 proposes to understand factors that control the hydrolysis reactions of tetracalcium phosphate (TTCP), alpha-tricalcium phosphate (alpha-TCP), dicalcium phosphate dihydrate (DCPD), dicalcium phosphate anhydrous (DCPA) and calcium hydroxide. These calcium phosphate salts are the major components of different CPCs. Hydrolysis of one or more of the salts that form hydroxyapatite (HA) is responsible for the hardening of the cement. A better understanding of the hydrolysis reaction of each of these salts will provide important insights into factors that influence some important cement properties, including the rate of conversion to HA, formation of Ca-deficient or stoichiometric HA, the crystallinity HA, etc. Defective or non-stoichiometric HAs are believed to be more bioresorbable. Aim 2 proposes to study the dissolution rate of cement products in demineralizing solutions having ionic compositions mimicking the acidic environment produced by osteoclasts. A dual constant-composition titration system was developed during the report period for measuring dissolution rates of calcium phosphate biomaterials under simulated acidified physiological solutions. The Principal Investigator proposes to use this technique as an in vitro model for predicting resorption rates of CPC and to understand factors that control the dissolution rate. Aim 3 proposes to study properties of non-rigid and resorbable calcium phosphate cements. Experiments are described to study composites of CPC and chitosan, a biocompatible polymer to form self-hardening, bioresorbable, and non-rigid bone graft materials. These materials should be useful in a number of applications in which the implant can remain stable and firmly attached to the bone defect surface despite micro-movements of the defect walls. Aim 4 will study properties of injectable premixed calcium phosphate cement pastes. Premixed CPC pastes have the advantages that they are stable in the package and harden only after delivery to the defect site where the non-aqueous liquid is replaced by water from the surrounding tissue. While premixed CPC is considerably easier to use and is injectable, its properties are quite different from the conventional CPCs. The hardening time, resistance to washout, and HA conversion of premixed pastes consisting of CPC powder and non-aqueous liquids, such as glycerin, will be studied. The Principal Investigator also proposes to determine mechanical properties of the hardened CPC pastes.