Development and Characterization of Tunable Hydrogel Nanoparticle Assemblies
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Microgels are colloidally stable, hydrogel nanoparticles that have previously been used in biomaterial applications due to their tunable mechanical and chemical properties. In particular, this work focuses on developing enabling routes to fabricate 2D and 3D polymeric assemblies designed with the intent to either direct, inhibit, or promote cellular proliferation. First, the development of raspberry-like particles (RLPs) is explored using colloidal-phase mediated heteroaggregation. RLPs are composed of a microgel shell assembled atop a polystyrene (PS) core particle. RLPs were fabricated using microgel dispersions of varied φ with microgels composed of either poly(N-isopropylacrylamide) (pNIPAm) or poly(N-isopropylmethacrylamide) (pNIPMAm) and cross-linked with either 1 mol-% or 5 mol-% N,N’- methylenebis(acrylamide) (BIS). Microgel coverage was assessed via SEM imaging and qNano translocation. PNIPAm microgels are able to coat PS cores at all φ due to their loose network structure regardless of cross-linker content. In contrast, pNIPMAm microgel coating is highly dependent on percent cross-linker and φ. Comparison of SEM and qNano data indicates that the qNano can be used as a high-throughput method to analyze RLP surface coverage. The development of raspberry-like patchy particles (RLPPs), containing two microgel populations assembled atop a PS core, using the same method is also explored. Coatings composed of pNIPAm microgels containing either 1 mol-% or 5 mol-% BIS exhibit a higher degree of packing and order than coatings comprised of pNIPAm and pNIPMAm microgels containing 5 mol-% BIS. To increase microgel packing, a two-step fabrication method is explored revealing the ability to fabricate RLPPs with highly packed coatings. After fabrication scale-up, biocompatibility of RLPs within aggregates of embryonic stem cells is investigated. Loading and release studies, incorporation studies, and gene expression analysis were performed. RLPs incorporated within stem cell aggregates are able to direct cell fate through delivery of a biomacromolecule. The development of polyelectrolyte microgel films is explored using the established layer-by-layer method. Microgel films were constructed from anionic microgels and polycations such as poly(diallyldimethylammonium chloride) and polyethyleneimine (PEI). Microgels were composed of pNIPAm, the co-monomer acrylic acid (AAc) (30 mol-%), and the cross-linker BIS (4 mol-%) or poly(ethylene glycol) diacrylate. Using these microgel-based films, the mechanical properties of the film were modulated via chemical cross-linking. AFM nanoindentation was used to assess micro-scale mechanical properties. Upon cross-linking, films exhibit an order of magnitude increase in Young’s modulus. Fibroblasts adhere preferentially to stiffer microgel films. Additionally, cell number and cell spreading are not commensurate with protein adsorption values. Finally, the development of 2D and 3D polyelectrolyte constructs is explored to establish the versatility of an innovative fabrication technique. PNIPAm-co-AAc microgels with either 4 mol-% BIS or no cross-linker, PS beads, and RLPs were used as building blocks in conjunction with PEI. Microgel films, laterally patterned microgel films and PS films, perpendicularly patterned microgel films, RLP films, and bulk polyelectrolyte microgel gels were characterized via AFM, SEM, confocal microscopy, and brightfield microscopy. Microgel films exhibit non-linear film buildup. Microgel films fabricated at varied thicknesses exhibit Young’s moduli ranging from 5 kPa to 101 kPa. Laterally patterned constructs exhibit micron-scale features. Perpendicular patterning is established using microgels with varied chemical and/or mechanical properties. Bulk polyelectrolyte gels were also fabricated and characterized via oscillatory rheology; mechanical properties are similar and reminiscent to an elastic system on the region where experiments were performed. Cellular adhesion studies performed on laterally patterned microgel and PS films demonstrate that pattern features influence cellular behavior. Finally, microgel films are explored as a biomedical device designed to augment blood clotting. Clotting studies were performed in vitro and assessed via confocal microscopy. Microgel films soaked in solutions with varied pH and salt concentration augment blood clotting.