Design and development of a bioresorbable bone graft

描述(由申请人提供)：该项目的长期目标是开发一种安全、成本效益高、现成、性能良好的骨填充材料，其基础是从血液副产品中提取的塑料。美国每年进行的骨科手术超过80万例，随着美国人口老龄化，这一数字只会继续增长。然而，目前的材料，包括自体移植、同种异体移植和工程生物材料，都没有达到临床预期，原因包括成本、疾病传播问题、骨捐赠问题和并发症，以及缺乏具有良好特性和一致性能的产品。血液副产品塑料有可能克服这些限制。第一阶段的假设是，这些塑料可以被设计成具有所需的机械和降解性能，在体外表现出生物相容性，并在体内临界大小的缺损区模型中导致骨形成。为了验证这一假设，我们将检验各种塑料配方的杨氏模数。这些塑料的体外降解，在细胞蛋白酶存在的情况下，然后将进行光谱分析。然后，将使用标准的商业测试来研究具有良好机械和降解性能的塑料在体外的生物兼容性和对培养细胞的增殖作用。最后，在一项利用小鼠颅骨缺损模型进行的先导性研究中，将研究体内骨形成能力。在第二阶段，将使用两个标准化的动物骨缺损模型进行更大规模的调查，以进一步开发这些塑料，并为FDA提交的初步数据提供。公共卫生相关性：人口老龄化加上他们活动的增加，增加了对有效骨移植材料的需求。由于结果不一致、供应不足和成本等原因，目前的临床材料没有达到临床医生的许多期望。Carmell已经开发出一种由人类血液副产品制成的材料，这种材料有可能成为一种安全、经济、现成和一致的骨移植疗法。

DESCRIPTION (provided by applicant): The long-term goal of this project is to develop a safe, cost-effective, off-the-shelf, and well characterized bone filler material based on plastics derived from blood byproducts. Over 800,000 bone procedures are performed in the US per year, and with the aging US population, this number will only continue to grow. However, current materials, including autografts, allografts, and engineered biomaterials, all fall short of clinical expectations for reasons such as cost, disease transmission concerns, bone donation issues and complications, and lack of well characterized and consistently performing products. Blood byproduct-based plastics have the potential to overcome these limitations. The Phase I hypothesis is that these plastics can be engineered to have desired mechanical and degradation properties, demonstrate biocompatibility in vitro, and lead to bone formation in an in vivo critical-sized defect model. To test this hypothesis, the Young's Modulus of various plastic formulations will be examined. In vitro degradation of these plastics, in the presence of cellular proteases, will then be examined spectroscopically. Plastics with desirable mechanical and degradation properties will then be studied for their in vitro biocompatibility and proliferative effect on cultured cells using standard commercial assays. Finally, in vivo bone formation capacity will be investigated in a pilot study utilizing a mouse calvarial defect model. In Phase II, larger scale investigations in two standardized animal bone defect models will be used to further develop these plastics and provide preliminary data for FDA submission. PUBLIC HEALTH RELEVANCE: The aging population coupled with their increased activity has raised demand for effective bone graft materials. Current clinical materials fall short of many of the expectations of clinicians for reasons such as inconsistent outcomes, inadequate supply, and cost. CarMell has developed a material made from human blood byproducts that has the potential to be a safe, cost-effective, off-the-shelf, and consistent bone graft therapy.