Structure-function relationships in biomaterials for tissue engineering applications

为了加强加拿大在生物医学技术方面的领导地位，我提出了一个研究计划，旨在通过开发生物材料驱动的解决方案来解决组织工程中的长期问题和当前挑战。特别是，我将研究在界面和3D基质中管理细胞行为的仍未探索的结构-功能关系，以产生基本的新知识，以指导设计更有效的生物材料，应用于骨、肠道和子宫组织工程。 具体地说，在接下来的五年里，我提出了一种新的实验方法，通过模拟骨骼微生理学的关键方面的体外细胞培养模型来研究界面现象，以解释控制细胞对具有不同几何形状和无序的纳米管的反应的机制。这项研究的结果将建立新的体外实践和预测模型，为生物医学植入物市场准确评估纳米钛表面的骨传导潜力。 此外，我还将根据水凝胶在体外促进肠神经相关功能的能力来开发和优化水凝胶，解决目前缺乏系统工作重点的有效方法，以支持肠神经前体分化和肠神经支配的恢复。这项研究将导致创造可注射的无细胞支架来直接恢复肠道的神经支配，并创造可调的基质来包裹和输送用于干细胞治疗的肠神经前体细胞。最后，我将根据水凝胶同时促进子宫内膜细胞定植和侵袭的能力来调查和筛选水凝胶。其目标是开发新的子宫贴片，能够诱导修复子宫疤痕和损伤，同时增加疤痕部位的可存活组织体积，为胎盘植入提供更有利的环境，最终有利于积极的妊娠结果。 最终，拟议的研究将在生物医学战略和技术的设计和应用方式上产生深刻的变革：成本效益高、生物材料驱动的替代方案将确保加拿大在生物医学研究和产业创新方面的领导地位继续增长。

To contribute to strengthen Canada's leadership in biomedical technologies, I propose a research program aimed at addressing both long-standing problems and current challenges in tissue engineering by developing biomaterials-driven solutions. In particular, I will investigate still unexplored structure-function relationships governing cell behaviour at interfaces and in 3D matrices to generate the fundamental new knowledge required to instruct the design of more effective biomaterials for applications in bone, gut and uterine tissue engineering. Specifically, over the course of the next five years, I propose a new experimental approach to study interfacial phenomena with an in vitro cell culture model that mimics key aspects of bone micro-physiology in order to explain the mechanisms that control how cells response to nanopatterns with variable geometry and disorder. Results from this research will establish new in vitro practices and predictive models for the accurate assessment of the osteonductive potential of nanopatterned titanium surfaces for the biomedical implants market. In addition, I will develop and optimize hydrogels based on their in vitro ability to promote relevant functions of enteric neurons, addressing the current lack of systematic work focus on effective methods to support enteric neuronal progenitor differentiation and restoration of gut innervation. This research will lead to the creation of both injectable cell-free scaffolds to directly restore innervation in the gut and of tunable matrices for the encapsulation and delivery of enteric neuron progenitors for stem-cell therapies. Lastly, I will investigate and screen hydrogels based on their ability to simultaneously promote endometrial cell colonization and invasion. The goal is the development of novel uterine patches capable of inducing repair of uterine scars and injuries while, at the same time, thickening the viable volume of tissue at the site of the scar to provide a more favorable environment for placentation, ultimately favouring a positive outcome of pregnancy. Ultimately, the proposed research is poised to create profound transformations in the ways biomedical strategies and technologies are designed and applied: cost-effective, biomaterials-driven alternatives will ensure continued growth of Canada's leadership in biomedical research and industrial innovation.