Novel Enabling Technologies for Regenerative Medicine and Tissue Engineering

心血管疾病，如冠状动脉阻塞是加拿大的主要死因之一。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，例如冠状动脉血管成形术和支架植入术，以及（iii）治疗性血管生成。这些选择中的每一个都有其自身的缺点，阻碍了充分的临床潜力。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，而冠状动脉血管成形术和支架植入术受到最终重新闭塞动脉的平滑肌细胞的不期望的和不受控制的增殖的限制。治疗性血管生成需要将生长因子受控地递送到所需部位，因此至今还不可能。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，以解决上述限制，通过1）增强氧气输送，以加速组织工程血管移植物，2）功能性固定Jagged1蛋白支架模拟表面，和3）设计可生物降解的氨基酸衍生纤维基质输送血管生成因子。拟议的研究建立在申请人及其合作者过去跨学科研究工作的基础上，这些研究工作将化学工程、材料科学以及细胞和分子生物学联系起来。拟议研究计划的动机是获得开发下一代技术所需的理解，以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。主要目标是培养全面发展的毕业生，他们具有良好的技术，科学，领导力和创业技能，这些技能由综合跨学科的综合研究培训计划培养。总的来说，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。这项研究预计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.