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

点击翻译按钮获取中文摘要

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.