New Functionally-Graded Biohybrid Vascular Graft

新型功能分级生物混合血管移植物

基本信息

批准号：
8907500
负责人：
Yogesh K. Vohra
金额：
$ 2.5万
依托单位：
VIVO BIOSCIENCES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-04-15 至 2015-04-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8907500
关键词：
Adhesions Affect Animals Arteries Biocompatible Materials Biomechanics Biomedical Engineering Bioreactors Blood Circulation Blood Pressure Blood Vessels Bypass Caliber Canis familiaris Cell Adhesion Cells Collagen Coronary Coronary Artery Bypass Coronary Vessels Development Devices Drug Formulations Elastin Endothelial Cells Endothelium Engineering Evaluation Exhibits Extracellular Matrix Failure Family suidae Future Generations Goals Growth Growth Factor Guidelines Human Hybrids Hyperplasia Implant In Vitro Joints Maintenance Marketing Mechanics Memory Methods Modeling Muscle Fibers Natural regeneration Oryctolagus cuniculus Outcome Patients Peripheral Phase Physiological Pilot Projects Polymers Polytetrafluoroethylene Principal Investigator Process Property Prosthesis Proteins Protocols documentation Quality Control Regenerative Medicine Resistance Saphenous Vein Shapes Side Small Business Technology Transfer Research Structure Surgical sutures System Technology Tensile Strength Testing Thrombosis Tissue Engineering Tissues Tubular formation Vascular Endothelial Cell Vascular Graft base biomaterial compatibility cell growth cell type commercial application dacron density design femoral artery immunogenic implantation improved in vivo in vivo Model novel phase 2 study physical property polycaprolactone preclinical evaluation public health relevance research and development response scaffold scale up technological innovation tissue regeneration validation studies vascular tissue engineering

项目摘要

DESCRIPTION (provided by applicant): In this Phase I STTR proposal, our R&D goal is the development and evaluation of a novel functionally-graded biohybrid vascular graft for small diameter (<6 mm) coronary bypass applications. Tissue engineered vascular constructs developed to date have mostly utilized synthetic and animal- derived biomaterials and require pre-seeding of host cells before implantation to overcome the complications of prosthetic vascular grafts. However, these graft systems exhibit many limitations including poor cellular adhesion, inadequate biomechanical and functional properties. The PI has recently demonstrated an in vitro regenerated human endothelium on functionally-layered polymeric scaffolds containing bioactive proteins. Moreover, VBI has developed a unique human biomatrix (HuBiogel) that allows viable tissue constructs by cultivating single or multiple cell types. HuBiogel milieu can also be controlled via enrichment with specific growth factors (VEGF). We now propose to combine our functionally-layered graft strategy with this physiological HuBiogel technology for fabricating an advanced 3D vascular construct demonstrating enhanced lumen endothelialization and biocompatibility and structural integrity. Phase I specific aims are: 1) Fabricate and optimize functionally layered HuBiogel-biohybrid scaffolds (4 mm ID) with promising biomechanical properties using our sequentially co-spun HuBiogel/polymer nanomatrix formulation protocol; and 2) Evaluate in vitro anti-thrombogenicity, biocompatibility and functionality of new HuBiogel-hybrid graft with human vascular endothelial and skeletal muscle cells using established bioreactor culture methods. In addition, a pilot animal study will be performed to demonstrate in vivo biomechanical integrity of new vascular graft by implanting in rabbit aorto-iliac model. We anticipate that new biohybrid device engineered with bioactive HuBiogel (functional endothelium) and polymeric gradient (robust biomechanics) will provide an improved ready-to-implant for small diameter grafting without requiring pre-seeding of primary cells. Thus, successful development of prototypic biohybrid vascular graft will form important basis for detailed quality control analyses and in vivo animal validation studies (dog or pig coronary bypass models) in future Phase II. For this STTR proposal, a dedicated team of bioengineers, cell biologist and cardiologists is gathered to develop and commercialize a novel small- diameter human vascular graft for coronary replacement. Potential for technological innovation and commercial application: No biohybrid vascular graft employing human biomatrix scaffold design is currently in market. We anticipate that a ready-to- implant or graft device will have worldwide market for the bypass treatments, estimated to be in millions of dollar.

描述（由申请人提供）：在第一阶段 STTR 提案中，我们的研发目标是开发和评估用于小直径（<6 毫米）冠状动脉搭桥应用的新型功能分级生物混合血管移植物。迄今为止开发的组织工程血管结构大多采用合成和动物源性生物材料，并且需要在植入前预先接种宿主细胞，以克服人工血管移植物的并发症。然而，这些移植系统表现出许多局限性，包括细胞粘附性差、生物力学和功能特性不足。 PI 最近在含有生物活性蛋白的功能层状聚合物支架上展示了体外再生的人内皮。此外，VBI 还开发了一种独特的人类生物基质 (HuBiogel)，可通过培养单一或多种细胞类型来构建可行的组织。 HuBiogel 环境也可以通过富集特定生长因子 (VEGF) 来控制。我们现在建议将我们的功能分层移植策略与这种生理 HuBiogel 技术相结合，以制造先进的 3D 血管构建体，展示增强的管腔内皮化、生物相容性和结构完整性。第一阶段的具体目标是：1) 使用我们的顺序共纺 HuBiogel/聚合物纳米基质配方方案，制造和优化功能分层的 HuBiogel-生物混合支架（内径 4 mm），具有良好的生物力学性能； 2) 使用已建立的生物反应器培养方法，评估新型 HuBiogel 混合移植物与人血管内皮细胞和骨骼肌细胞的体外抗血栓形成性、生物相容性和功能性。此外，还将进行一项试点动物研究，通过植入兔主动脉-髂骨模型来证明新血管移植物的体内生物力学完整性。我们预计，采用生物活性 HuBiogel（功能性内皮）和聚合物梯度（强大的生物力学）设计的新型生物混合装置将为小直径移植提供改进的即用型移植，无需预先接种原代细胞。因此，原型生物混合血管移植物的成功开发将为未来第二阶段的详细质量控制分析和体内动物验证研究（狗或猪冠状动脉搭桥模型）奠定重要基础。对于这个 STTR 提案，一个由生物工程师、细胞生物学家和心脏病学家组成的专门团队聚集在一起，开发一种用于冠状动脉置换的新型小直径人体血管移植物并将其商业化。技术创新和商业应用潜力：目前市场上还没有采用人体生物基质支架设计的生物混合血管移植物。我们预计，准备植入或移植的装置将拥有全球搭桥治疗市场，估计价值数百万美元。