CALCIUM PHOSPHATE BONE REPAIR MATERIALS

描述(申请人提供)：第一个自硬性磷酸钙骨水泥(CPC)是在我们实验室根据目前和以前的N1H资助开发的。自1996年以来，一种这样的CPC材料一直在临床上用于修复人类的颅骨缺陷。近年来，FDA已经批准了几种额外的CPC，但由于物理和体内特性的限制，它们的用途主要局限于颅面和选定的非承重骨科应用。通过以下目标，本提案的目标是确定如何将对不同应用至关重要的那些属性构建到CPC材料中，从而使CPC材料能够用于更广泛的临床应用。 目的1.开发和研究CPC的性质，所形成的产品具有广泛的相组成和吸收率，适合不同的临床应用。 目的2.开发和研究弹性体CPC材料的性能，为组织内的微运动提供顺应性，并防止骨折。具有这些特性的材料应该在牙周修复、牙槽骨隆起和脊柱融合等方面有应用价值。 目的3.开发和研究在包装内稳定、在组织缺损处硬化的快速固化的可模塑/可注射预混复合体的性能。这些CPC可以更容易地输送到缺损处，并可能减少手术侵袭。 目的4.在动物模型中评价前三个目标中筛选出的磷酸钙骨水泥材料的体内性质。将进行以下三项动物研究：(1)评估在目标1中开发的新型CPC材料的体内吸收率，这些材料具有广泛的体外酸溶解速率。这项研究将采用狗模型，并将使用组织病理学测量和电子探针分析来获得体内吸收/骨替代率的定量数据。(2)对AIM开发的非刚性壳聚糖的体内特性进行评价2.本研究采用犬模型，重点研究了CPC和壳聚糖组分在体外酸溶解速率相近的CPC-壳聚糖复合材料的生物相容性、骨吸收和骨替代。(3)在狗模型中评价预混可注射CPC，以确定这些材料的生物相容性和骨传导性，这些材料含有先前研究中未在体内评估的非钙磷酸盐成分。

DESCRIPTION (provided by applicant): The first self-hardening calcium phosphate cements (CPCs) were developed in our laboratory under the present and a previous N1H grant. One such CPC material has been in clinical use since 1996 for repairing cranial defects in humans. In recent years, several additional CPCs have been approved by the FDA, but due to limitations in both physical and in vivo properties, their uses remain largely confined to craniofacial and selected non-load bearing orthopedic applications. Through the following Aims, the objective of the present proposal is to determine how to build into CPC materials those attributes that are of critical importance for different applications so that CPC materials can be useful for a wider range of clinical applications. Aim 1. To develop and study the properties of CPCs that form products comprising a wide range of phase compositions and resorption rates suitable for different clinical applications. Aim 2. To develop and study the properties of elastomeric CPC materials that would provide compliance for micro-motions within the tissues and resist fracturing. Materials with these properties should be useful for applications such as periodontal defect repair, ridge augmentation, and spinal fusion. Aim 3. To develop and study the properties of rapid setting moldable/injectable premixed CPCs that are stable in the package and harden at tissue defect site. These CPCs can be more easily delivered to the defect site and possibly with reduced surgical invasions. Aim 4. To evaluate in vivo properties of selected CPC materials developed in the first three Aims in animal models. The following three animal studies will be conducted: (1) Evaluation of in vivo resorption rates of new CPC materials developed in Aim 1 that exhibit a wide range of in vitro acid dissolution rates. The study will employ a dog model, and histopathological measurements and electron microprobe analyses will be used to obtain quantitative data on in vivo resorption/bone replacement rates. (2) Evaluation of in vivo characteristics of non-rigid CPCs developed in Aim 2. The study, employing a dog model, will focus on the biocompatibility and resorption and bone replacement of CPC-chitosan composites in which the CPC and chitosan components have closely matched in vitro acid dissolution rates. (3) Evaluation of premixed, injectable CPC in a dog model to determine biocompatibility and osteoconductivity of these materials, which contain non-calcium phosphate components that have not been evaluated in vivo in previous studies.