Design and development of a bioresorbable bone graft

描述（由申请人提供）：本项目的长期目标是开发一种安全、经济、现成且表征良好的骨填充材料，该材料基于血液副产品中的塑料。美国每年进行超过80万例骨手术，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，包括自体移植物、同种异体移植物和工程生物材料，由于成本、疾病传播问题、骨捐赠问题和并发症以及缺乏良好表征和一致性能的产品等原因，都达不到临床预期。基于血液副产品的塑料有可能克服这些限制。第一阶段假设是，这些塑料可以被设计成具有所需的机械和降解性能，在体外证明生物相容性，并导致在体内临界尺寸的缺损模型中形成骨。为了检验这一假设，将检查各种塑料配方的杨氏模量。在细胞蛋白酶的存在下，这些塑料的体外降解，然后将进行光谱检查。然后，将使用标准商业试验研究具有理想机械和降解性能的塑料的体外生物相容性和对培养细胞的增殖作用。最后，将利用小鼠颅骨缺损模型在初步研究中研究体内骨形成能力。在第二阶段，将在两个标准化动物骨缺损模型中进行更大规模的研究，以进一步开发这些塑料，并为FDA提交提供初步数据。公共卫生相关性：人口老龄化加上活动增加，提高了对有效植骨材料的需求。由于结果不一致、供应不足和成本等原因，目前的临床材料达不到临床医生的许多期望。CarMell开发了一种由人类血液副产品制成的材料，该材料有可能成为一种安全，具有成本效益，现成且一致的骨移植疗法。

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.