Structure-function relationships in biomaterials for tissue engineering applications

组织工程应用生物材料的结构-功能关系

• 批准号: RGPIN-2020-05945
• 负责人: Variola, Fabio
• 金额: $ 2.84万
• 依托单位: University of Ottawa
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=740932
• 关键词: Structure; function; relationships; biomaterials; tissue

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.

为了加强加拿大在生物医学技术方面的领导地位，我提出了一项研究计划，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长期存在的问题和当前的挑战。特别是，我将研究尚未探索的结构-功能关系，在界面和3D矩阵中控制细胞行为，以产生指导设计更有效的生物材料用于骨，肠道和子宫组织工程所需的基本新知识。具体来说，在接下来的五年中，我提出了一种新的实验方法来研究界面现象与体外细胞培养模型，模仿骨微生理学的关键方面，以解释控制细胞如何响应纳米粒子的机制与可变的几何形状和无序。这项研究的结果将建立新的体外实践和预测模型，用于准确评估生物医学植入物市场纳米图案化钛表面的骨诱导潜力。 此外，我将开发和优化水凝胶的基础上，他们在体外促进肠神经元的相关功能的能力，解决目前缺乏系统的工作重点有效的方法来支持肠神经元祖细胞分化和恢复肠道神经支配。这项研究将导致创建可注射的无细胞支架，以直接恢复肠道中的神经支配，以及用于封装和递送肠神经元祖细胞用于干细胞治疗的可调基质。最后，我将研究和筛选水凝胶的基础上，他们的能力，同时促进子宫内膜细胞定植和入侵。目标是开发新型子宫补片，其能够诱导子宫瘢痕和损伤的修复，同时增厚瘢痕部位的组织存活体积，为胎盘形成提供更有利的环境，最终有利于妊娠的积极结局。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面产生深刻的变革：具有成本效益的生物材料驱动的替代品将确保加拿大在生物医学研究和工业创新方面的领导地位持续增长。