Novel Manufacturing Processes for Tissue Engineered Vascular Grafts

组织工程血管移植物的新颖制造工艺

• 批准号: 8493166
• 负责人: Shannon L. M. Dahl
• 金额: $ 99.84万
• 依托单位: HUMACYTE, INC.
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-02-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8493166
• 关键词: Address; Agreement; Allogenic; Amendment; Animal Model; Antigens; Applied Research; Autologous; Basic Science; Bioreactors; Blood Vessels; Bypass; Caliber; Canis familiaris; Cardiovascular system; Cells; Clinical Data; Clinical Research; Clinical Trials; Complications of Diabetes Mellitus; Coronary Artery Bypass; Culture Media; Development; Dialysis procedure; Disease; Doctor of Philosophy; End stage renal failure; Engineering; Evaluation; Failure; Funding; Heart Diseases; Hematological Disease; Hemodialysis; Hospitals; Howard Temin Award; Human; Human Engineering; Human Resources; Hyperplasia; Implant; In Vitro; Information Systems; Investments; Kidney Failure; Life; Liquid substance; Lung diseases; Marketing; Mechanics; Mission; Modeling; Morbidity - disease rate; National Heart, Lung, and Blood Institute; Obesity; Operative Surgical Procedures; Papio; Patients; Peripheral; Peripheral Vascular Diseases; Pharmacologic Substance; Phase; Phase I/II Trial; Phase II Clinical Trials; Phase III Clinical Trials; Positioning Attribute; Primates; Production; Property; Protocols documentation; Regenerative Medicine; Regulation; Request for Applications; Resistance; Risk; Safety; Saphenous Vein; Secure; Services; Site; Sleep Disorders; Small Business Innovation Research Grant; Smooth Muscle Myocytes; System; Technology; Testing; Time; Tissue Engineering; Tissues; Trauma; Universities; Upper Extremity; Vascular Graft; Veins; Venous; Work; base; commercialization; cost; design; experience; follow-up; graft failure; human tissue; implantation; manufacturing process; meetings; member; nonhuman primate; novel; prototype; public health relevance; reconstruction; research and development; response; tissue regeneration; vascular tissue engineering

DESCRIPTION (provided by applicant): This Phase IIB SBIR application is responsive to NHLBI RFA HL-13-016, "NHLBI SBIR Phase IIB Bridge Awards to Accelerate the Commercialization of Technologies for Heart, Lung, Blood and Sleep Disorders and Diseases (R44)". This RFA solicits work on "basic, applied, and clinical research on all product and service development related to the mission of the NHLBI... including cardiovascular complications of diabetes and obesity, ... and peripheral vascular diseases." Humaycte has developed a novel vascular graft that has shown excellent function in large animal models. The graft is made by culturing allogeneic human smooth muscle cells in a bioreactor to produce an engineered vascular tissue, which is then carefully decellularized. Vascular dialysis grafts that are 6 mm in diameter function well in a baboon model of arterio-venous grafting. In our Phase II proposal, our aim was the construction and testing of a prototype, disposable vascular graft bioreactor. In this Phase IIB proposal, we will build on our successful Phase II work, and we will develop a closed, FDA-compliant manufacturing system that can produce manufacturing batches of 100 grafts/unit, enabling production sufficient to support clinical trials and eventual commercialization. This Phase IIB application will also support a Phase I/II clinical trial examining the safety and efficacy of the engineered vascular graft for hemodialysis access. Manufacturing data from this system, combined with clinical data from our Phase I/II trial, will be submitted to the FDA. At the conclusion of this study, we will file a Special Protocol Assessment (SPA) in support of a Phase III trial in the U.S. on Humacyte's vascular grafts in hemodialysis patients. These grafts have the potential to decrease morbidity from graft-related complications in patients with end-stage renal disease, as well as other patients requiring arterial bypass grafts.

描述（由申请人提供）：此阶段IIB SBIR应用对NHLBI RFA HL-13-016的反应，“ NHLBI SBIR SBIR阶段IIB桥奖，以加速心脏，肺，血液和睡眠障碍和睡眠障碍和疾病的技术商业化（R44）”。该RFA征求了“与NHLBI的使命相关的所有产品和服务开发的基础，应用和临床研究……包括糖尿病和肥胖症的心血管并发症，以及……以及外周血管疾病”。 Humaycte开发了一种新型的血管移植物，在大型动物模型中表现出了出色的功能。通过在生物反应器中培养同种异体平滑肌细胞以产生工程的血管组织来制作移植物，然后仔细脱细胞化。直径为6 mm的血管透析移植物在动脉染色的狒狒模型中很好地发挥了作用。在我们的第二阶段提案中，我们的目标是对原型，一次性血管移植生物反应器的构建和测试。 在此阶段IIB提案中，我们将以我们成功的II阶段工作为基础，我们将 开发一个封闭的，符合FDA的制造系统，该系统可以生产100个移植物/单位的制造批次，从而使生产足以支持临床试验和最终商业化。此阶段IIB应用还将支持I/II期临床试验，该试验检查工程血管移植物在血液透析中的安全性和功效。来自该系统的制造数据，结合我们I/II期试验的临床数据，将是 提交给FDA。在这项研究的结论中，我们将提交特殊的方案评估（SPA），以支持美国血液透析患者Humacyte的血管移植物的III期试验。这些移植物具有终末期肾脏疾病患者以及其他需要动脉旁路移植物的患者的移植相关并发症的发病率。