Novel Enabling Technologies for Regenerative Medicine and Tissue Engineering

冠状动脉闭塞等心血管疾病是加拿大的主要死亡原因之一。对于患有严重冠状动脉疾病的患者，有三种治疗选择：(i)冠状动脉旁路移植术，（ii）基于导管的干预，如冠状动脉成形术和支架置入术，以及（iii）治疗性血管生成。每一种选择都有其自身的缺点，阻碍了充分发挥临床潜力。外科旁路移植术的成功受到缺乏工程化生物组织替代物的限制，而冠状动脉成形术和支架植入术则受到平滑肌细胞不希望和不受控制的增殖的限制，平滑肌细胞最终会再次阻塞动脉。治疗性血管生成需要有控制地将生长因子输送到所需部位，因此目前尚不可能。在接下来的5年里，我的研究项目将专注于开发新的技术来解决上述局限性：1)增强氧输送以加速组织工程血管移植，2)Jagged1蛋白在支架模拟表面的功能固定，以及3)设计可生物降解的氨基酸衍生纤维基质用于输送血管生成因子。申请人及其合作者在化学工程、材料科学、细胞和分子生物学等领域的跨学科研究成果的基础上进行了拟议的研究。该研究计划的动机是获得开发用于未来血管疾病干预的下一代技术所需的理解，并获得该领域的基础专业知识。主要目标是通过综合跨学科综合研究培训计划培养具有良好技术，科学，领导和创业技能的全面发展的毕业生。总体而言，该计划将为3名博士，2名MESc和一些本科生提供培训，让他们接触前沿研究。预计这项研究将导致重大的技术发展，用于未来的人类健康和加拿大的经济利益。

Cardiovascular diseases such as coronary artery occlusion is one of the leading causes of death in Canada. For patients with severe coronary artery disease, there are three treatment options: (i) coronary artery bypass grafting, (ii) catheter based interventions such as coronary angioplasty and stenting, and (iii) therapeutic angiogenesis. Each of these options has its own drawback impeding the full clinical potential. The success of surgical bypass grafting is limited by the lack of an engineered biological tissue substitute whereas coronary angioplasty and stenting is limited by the undesired and uncontrolled proliferation of smooth muscle cells that eventually re-occlude the artery. Therapeutic angiogenesis requires controlled delivery of growth factors into the desired site and thus has not been possible as yet. Over the next 5 years, my research program will focus on developing novel enabling technologies to address the above-listed limitations by 1) enhancing oxygen delivery to accelerate tissue engineered vascular grafts, 2) functional immobilization of Jagged1 protein to stent-mimic surfaces, and 3) designing biodegradable amino acid derived fibrous matrix for delivery of angiogenic factors. The proposed research builds on the strengths of past interdisciplinary research efforts undertaken by the applicant and his collaborators bridging chemical engineering, materials science, and cellular and molecular biology. The motivation of the proposed research program is to obtain the understanding required to develop the next generation of technologies for applications in future vascular disease interventions and garner fundamental expertise in this area. The key objective is to train well-rounded graduates with sound technical, scientific, leadership, and entrepreneurial skills groomed by integrated interdisciplinary comprehensive research training program. Overall, the program will provide training for 3 PhD, 2 MESc and number of undergraduate students by exposing them to cutting-edge research. This research is expected to result in significant technology development for applications in future human health and economic benefit to Canada.