CALCIUM PHOSPHATE BONE REPAIR MATERIALS

描述（由申请人提供）：第一批自硬化磷酸钙水泥（CPC）是在我们实验室目前和之前的N1 H资助下开发的。自1996年以来，一种这样的CPC材料已用于临床修复人类颅骨缺损。近年来，FDA已批准了几种其他CPC，但由于物理和体内性质的限制，其用途仍主要限于颅面和选定的非承重骨科应用。通过以下目标，本提案的目的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，以便CPC材料可用于更广泛的临床应用。 目标1。开发和研究CPC的特性，这些CPC形成的产品包含适用于不同临床应用的各种相组成和吸收速率。 目标2.开发和研究弹性CPC材料的性能，为组织内的微动提供顺应性并抵抗断裂。具有这些特性的材料应该可用于诸如牙周缺损修复、牙槽嵴增高和脊柱融合的应用。 目标3。开发和研究快速凝固的可模塑/可注射预混CPC的性能，这些CPC在包装中稳定，并在组织缺损部位硬化。这些CPC可以更容易地输送到缺损部位，并可能减少手术侵入。 目标4。在动物模型中评价前三个目标中开发的选定CPC材料的体内特性。将进行以下三项动物研究：（1）评价目标1中开发的新型CPC材料的体内再吸收率，这些材料显示出广泛的体外酸溶解率。本研究将采用犬模型，并将使用组织病理学测量和电子探针分析获得体内再吸收/骨替代率的定量数据。(2)目标2中开发的非刚性CPC的体内特性评价。该研究采用犬模型，将重点关注CPC-壳聚糖复合材料的生物相容性、再吸收和骨替代，其中CPC和壳聚糖组分具有密切匹配的体外酸溶解速率。(3)在犬模型中评价预混的可注射CPC，以确定这些材料的生物相容性和骨传导性，这些材料含有非磷酸钙成分，这些成分在先前的研究中尚未在体内进行评价。

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.