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、经济、现成且特性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（如脱矿骨基质（DBM））、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持续性能的产品等原因，都达不到临床预期。基于血浆的塑料有可能克服这些限制。在一期研究中，Carmell Therapeutics证明了血浆基塑料具有生物相容性、可生物降解性和生物活性，并能在小鼠颅骨缺损模型中形成骨。在第二阶段，Carmell寻求开发一种软性塑料，并获得安全性和有效性数据，用于向FDA提交上市前批准申请。为了实现这一目标，该腻子将被设计成具有与dbm腻子相似的物理特性，同时保持原始血浆基塑料的生物相容性和生物活性特性。还将开发配套的腻子输送装置。该产品的成骨诱导潜能将在大鼠肌袋异位骨模型中进行测试。该产品修复兔长骨桡骨缺损的能力也将在一个大型的统计研究中进行测试。最后，将进行一系列生物测试，以满足FDA规定的医疗器械生物评价ISO 10993标准。

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.