Novel Enabling Technologies for Regenerative Medicine and Tissue Engineering

心血管疾病，如冠状动脉闭塞，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植入，以及(Iii)治疗性血管生成。这些选择中的每一个都有自己的缺点，阻碍了充分的临床潜力。外科搭桥术的成功受限于缺乏工程化的生物组织替代品，而冠状动脉血管成形术和支架植入术则受限于不受欢迎的和不受控制的平滑肌细胞增殖，最终导致动脉重新闭塞。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，因此目前还不可能。在接下来的5年里，我的研究计划将专注于开发新的使能技术，通过1)增强氧气输送来加速组织工程化血管移植，2)将Jagged1蛋白功能性固定到支架模拟表面，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。拟议的研究建立在申请人及其合作者过去进行的跨学科研究努力的优势之上，这些研究努力架起了化学工程、材料科学以及细胞和分子生物学之间的桥梁。拟议研究计划的动机是获得所需的理解，以开发下一代技术，应用于未来的血管疾病干预，并获得该领域的基本专业知识。主要目标是通过综合跨学科综合研究培训计划培养具有健全的技术、科学、领导力和创业技能的全面发展的毕业生。总体而言，该计划将通过让本科生接触尖端研究来为3名博士、2名MESc和一些本科生提供培训。这项研究预计将导致重大的技术开发，应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.