Engineered Mineral Nanoparticles and Nanocomposites: A Versatile Multifunctional Platform for 3D Bioprinting and Tissue Engineering

工程矿物纳米颗粒和纳米复合材料：用于 3D 生物打印和组织工程的多功能平台

• 批准号: RGPIN-2020-06497
• 负责人: Paul, Arghya
• 金额: $ 2.77万
• 依托单位: University of Western Ontario
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=746698
• 关键词: Engineered; Mineral; Nanoparticles; Nanocomposites; Versatile

The primary goal of this proposal is to develop a new class of biomaterials using engineered mineral nanoparticles to obtain three-dimensional (3D) complex structures consisting of cells and matrices using bioprinting technology. In the long-term, I intend to utilize mineral-based biomaterials as a platform technology to fabricate cell-instructive scaffolds with user-defined structures for advanced tissue engineering. However, without understanding how different minerals (e.g. calcium, magnesium, silicon, zinc, copper) regulate cellular activities, it is impossible to develop effective mineral-based biomaterials. A systematic investigation of the interactions between cell-cell, cell-nanoparticles, cell-matrix will lead us to the overarching goal. In the short term (next 5 years), I propose following three objectives that fit into the long-term goal: 1) To design mineral-based nanoparticles and elucidate their individual and synergistic effects on cellular behavior via combinatorial screening. This will provide new insight in deciphering the mechanisms by which mineral nanoparticles interact with the cells (male and female origin). We will identify new bioactive nanoparticle formulations that can effectively control cell behavior, without using any other stimulants. To our knowledge no other investigation has tailored nanoparticle compositions to engineer cell fate. 2) To develop 3D printable hydrogels using mineral nanoparticles with tailored cell-instructive properties. This objective will reveal the type of interactions between mineral nanoparticles, polymeric hydrogels and human cells, and create mechanically resilient, 3D-printable, bioresponsive hydrogels. This objective will also promote the field's understanding on how to leverage non-covalent interactions to mechanically reinforce weak polymeric networks and form tough, injectable, self-healing hydrogels. 3) To determine the ability of the printable hydrogels to bioprint complex tissue structures and direct cellular behavior. Utility of conventional hydrogel bioinks to print functional tissues and control cell fate is severely constrained by their suboptimal mechanical properties and limited bioactivity. To overcome these challenges, mineral-based hydrogel bioinks with tunable biological and mechanical properties will be used to engineer tissue constructs with high structural stability and precise spatio-temporal control over cell fate. Upon completion, this research will have broad scientific, engineering and technological impacts on the end-users (e.g. biofabrication and biomanufacturing industries) with potential to transform bioactive materials development, 3D printing and tissue engineering. HQP supported by this grant will receive state-of-the-art experiential training in nanomaterials, polymer science, stem cell biology and bioprinting technologies. HQP trained in these interdisciplinary technologies are highly sought in academic and industrial R&D sectors across Canada.

该提案的主要目的是使用工程矿物纳米颗粒开发新的生物材料，以获得由使用生物打印技术组成的细胞和矩阵组成的三维（3D）复杂结构。从长远来看，我打算利用基于矿物质的生物材料作为一种平台技术来制造使用用户定义的高级组织工程结构来制造细胞结构脚手架。但是，在不了解不同的矿物（例如钙，镁，硅，锌，铜）如何调节细胞活性的情况下，不可能开发有效的基于矿物质的生物材料。对细胞细胞，细胞 - 纳米颗粒，细胞矩阵之间相互作用的系统研究将使我们达到总体目标。在短期（接下来的5年）中，我建议以下三个适合长期目标的目标：1）设计基于矿物质的纳米颗粒并通过组合筛选对细胞行为阐明其个体和协同作用。这将提供新的见解，以解释矿物纳米颗粒与细胞相互作用的机制（雄性和女性起源）。我们将确定新的生物活性纳米颗粒制剂，可以有效地控制细胞行为，而无需使用任何其他兴奋剂。据我们所知，没有其他调查为工程细胞命运定制纳米颗粒组成。 2）使用具有量身定制的细胞结构特性的矿物纳米颗粒开发3D可打印水凝胶。该目标将揭示矿物纳米颗粒，聚合物水凝胶和人类细胞之间的相互作用类型，并产生机械弹性的3D打印，生物辅助水凝胶。该目标还将促进该领域对如何利用非共价相互作用来机械增强弱聚合物网络并形成坚硬，可注射，自我修复水凝胶的理解。 3）确定可打印水凝胶对生物包含复合组织结构和直接细胞行为的能力。常规水凝胶生物互联物以打印功能组织和控制细胞命运的效用受到其次优的机械性能和有限的生物活性的限制。为了克服这些挑战，具有可调生物学和机械性能的基于矿物质的水凝胶生物学将用于设计具有较高结构稳定性和精确时空控制细胞命运的组织结构。 完成后，这项研究将对最终用户（例如生物制造和生物制造行业）产生广泛的科学，工程和技术影响，具有改变生物活性材料开发，3D打印和组织工程的潜力。该赠款支持的HQP将接受纳米材料，聚合物科学，干细胞生物学和生物构图技术的最先进的体验培训。在加拿大的学术和工业研发部门中，受过这些跨学科技术培训的HQP受过培训。