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，以加速心脏，肺，血液和睡眠障碍和疾病（R44）技术的商业化”。该RFA征求“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”的工作。包括糖尿病和肥胖的心血管并发症和外周血管疾病。“Humaycte开发了一种新型血管移植物，在大型动物模型中表现出出色的功能。移植物是通过在生物反应器中培养同种异体人平滑肌细胞来产生工程血管组织，然后仔细地脱细胞而制成的。直径为6 mm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原型，一次性血管移植生物反应器。 在这份IIB阶段的建议书中，我们将在第二阶段成功工作的基础上， 开发一个封闭的、符合FDA标准的生产系统，该系统可以生产100个移植物/单位的生产批次，使生产足以支持临床试验和最终的商业化。该IIB期申请还将支持I/II期临床试验，以检查用于血液透析通路的工程血管移植物的安全性和有效性。该系统的生产数据，结合我们I/II期试验的临床数据，将 提交给FDA。在本研究结束时，我们将提交一份特殊方案评估（SPA），以支持在美国进行的关于Humacyte血管移植物用于血液透析患者的III期试验。这些移植物有可能降低终末期肾病患者以及其他需要动脉旁路移植物的患者的移植物相关并发症的发病率。

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.