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

该提案的主要目标是利用工程矿物纳米颗粒开发一类新型生物材料，利用生物打印技术获得由细胞和基质组成的三维（3D）复杂结构。从长远来看，我打算利用矿物基生物材料作为平台技术，制造具有用户定义结构的细胞指导支架，用于高级组织工程。然而，如果不了解不同的矿物质（如钙、镁、硅、锌、铜）如何调节细胞活动，就不可能开发出有效的矿物生物材料。对细胞-细胞、细胞-纳米颗粒、细胞-基质之间相互作用的系统研究将引导我们达到首要目标。在短期内（未来5年），我建议以下三个目标符合长期目标：

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.