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、具有成本效益、现成且表征良好的基于血浆塑料的骨填充材料。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（例如脱矿骨基质（DBM））、同种异体移植物和工程化生物材料，由于诸如成本、疾病传播问题、骨捐献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。基于血浆的塑料有可能克服这些限制。在第一阶段，Carmell Therapeutics证明了基于血浆的塑料具有生物相容性，生物可降解性，生物活性，并在小鼠颅骨缺损模型中形成骨。在第二阶段，Carmell寻求开发一种腻子形式的塑料，并获得安全性和有效性数据，用于向FDA提交的上市前批准申请。为了实现这一目标，腻子将被设计为具有与基于DBM的腻子相似的物理特性，同时保持原始基于血浆的塑料的生物相容性和生物活性。还将开发一个配套的油灰输送装置。将在大鼠肌袋异位骨模型中测试产品的骨诱导潜力。还将在一项大型统计研究中测试产品修复兔长骨桡骨缺损的能力。最后，将进行一系列生物学试验，以满足FDA强制的ISO 10993医疗器械生物学评价标准。 公共卫生相关性：人口老龄化加上一般人群活动的增加，提高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，目前的临床材料达不到临床医生的许多期望。Carmell Therapeutics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 plasma. 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 (e.g. demineralized bone matrix (DBM)), 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 plasma-based plastics have the potential to overcome these limitations. In Phase I Carmell Therapeutics demonstrated that blood plasma-based plastics are biocompatible, biodegradable, bioactive, and form bone in a mouse calvarial defect model. In Phase II Carmell seeks to develop a putty-form of its plastic and obtain safety and efficacy data for use in a premarket approval application to the FDA. To achieve this, the putty will be designed to have similar physical properties to those of DBM-based putties while maintaining the biocompatibility and bioactivity properties of the original blood plasma-based plastic. An accompanying putty delivery device will also be developed. The osteoinductive potential of the product will be tested in a rat muscle-pocket heterotopic bone model. The ability of the product to repair a rabbit long bone radial defect will also be tested in a large, statistical study. Finally, a battery of biological tests will be performed to satisfy FDA- mandated ISO 10993 standards for the biological evaluation of medical devices. PUBLIC HEALTH RELEVANCE: The aging population coupled with the general population's 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 Therapeutics 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.