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第IIB期桥奖，以加快心、肺、血液和睡眠障碍和疾病(R44)技术的商业化”。该RFA征集关于“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……包括糖尿病和肥胖症的心血管并发症……和外周血管疾病”的工作。Humaycte已经开发出一种新的血管移植物，在大型动物模型中显示出出色的功能。这种移植物是通过在生物反应器中培养同种异体人类平滑肌细胞来产生工程化的血管组织，然后仔细地脱细胞制成的。直径为6 mm的血管透析移植物在动静脉动静脉移植物的狒狒模型中作用良好。在我们的第二阶段计划中，我们的目标是建造和测试一个原型，一次性血管移植生物反应器。在这个IIB阶段的提案中，我们将在成功的第二阶段工作的基础上再接再厉，我们将 开发一个封闭的、符合FDA标准的制造系统，该系统可以生产100个移植物/单位的制造批次，使生产足以支持临床试验和最终的商业化。这一IIB期应用还将支持一项I/II期临床试验，以检验用于血液透析通路的工程化血管移植物的安全性和有效性。该系统的制造数据，与我们I/II期试验的临床数据相结合，将是 提交给美国食品和药物管理局。在这项研究结束时，我们将提交一份特别方案评估(SPA)，以支持在美国进行的Humacyte血管移植在血液透析患者中的第三阶段试验。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的患者移植物相关并发症的发生率。

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.