| Tissue engineering offers promising therapies for tissue injury or damage through the in vivo delivery and construction of cell-laden hydrogel-based scaffolds. A common platform of interest for the encapsulation and delivery of cells to the site of injury is hydrogels formed from polyethylene glycol (PEG). Advances in polymer chemistry have produced hydrogels with well-controlled mesh size, mild polymerization conditions, cell immunopassivity, and controlled material degradation that can be safely integrated within living tissue. The mesh size dictated by molecular weight, governs bulk properties of hydrogel tissue scaffold. It is therefore difficult to simultaneously achieve conditions accommodating to cells (high molecular diffusivity) and to functional tissue (mechanical strength). This challenge is exacerbated by the need for the tissue microstructure to evolve over time in response to cellular growth and extracellular matrix production as natural tissue is formed.;The goal of this project is to employ droplet microfluidics to create microparticle-based hydrogel scaffolds that can be assembled in a bottom-up fashion. Microgel particles have been assembled into contiguous structures within a secondary polymer phase that was subsequently polymerized to form a composite scaffold. The hypothesis of my dissertation is that, by creating composite hydrogels from hydrogel microparticles, the mechanical and diffusive properties of the produced tissue scaffold can be effectively decoupled. The diversity of percolating particle structures that may be formed is broad and therefore provides the ability to tune composite mechanical properties across a wide range. The therapeutic focus of this thesis is aimed at articular cartilage engineering because while cartilage resembles a poly ethylene glycol (PEG) hydrogel, the initial scaffold properties strongly regulate the development of the final tissue. |
