Novel Manufacturing Processes for Tissue Engineered Vascular Grafts

描述（由申请人提供）：此IIB期SBIR申请响应NHLBI RFA HL-13-016，“NHLBI SBIR IIB期桥梁奖加速心脏、肺、血液和睡眠障碍和疾病技术的商业化（R44）”。该RFA征集“与NHLBI使命相关的所有产品和服务开发的基础、应用和临床研究……包括糖尿病和肥胖的心血管并发症……以及周围血管疾病。”Humaycte开发了一种新型血管移植物，在大型动物模型中显示出优异的功能。移植物是通过在生物反应器中培养异体人类平滑肌细胞来产生工程血管组织，然后仔细地去细胞化。直径为6mm的血管透析移植物在狒狒动静脉移植模型中功能良好。在我们的第二阶段提案中，我们的目标是构建和测试一个原型，一次性血管移植物生物反应器。在这个第三阶段的提案中，我们将以我们成功的第二阶段工作为基础，我们将

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.