
Silviya Zustiak, Ph.D.
Secondary Professor
Department of Biomedical Engineering
Studies on hydrogel biomaterials and tissue engineering, and development of novel biomaterials.
Research Interests
Biomaterial-based models are crucial for bridging the gap between traditional tissue culture and animal models by providing a cell environment that closely mimics real tissue. Novel biomaterials can be used as cell scaffolds, for drug screening platforms, to elucidate matrix structure-property relationships, and to assess cell-matrix interactions.
Dr. Zustiak also develops bioresorbable and injectable hydrogel and nanocomposite formulations as sustained release drug delivery devices. Her research is highly multidisciplinary, merging the fields of engineering, materials science, and biology.
Recent Publications
Tunable Viscoelasticity of Alginate Hydrogels via Serial Autoclaving
Tunable Viscoelasticity of Alginate Hydrogels via Serial Autoclaving
Alginate hydrogels are widely used as biomaterials for cell culture and tissue engineering due to their biocompatibility and tunable mechanical properties. Reducing alginate molecular weight is an effective strategy for modulating hydrogel viscoelasticity and stress relaxation behavior, which can significantly impact cell spreading and fate. However, current methods like gamma irradiation to produce low molecular weight alginates suffer from high cost and limited accessibility. Here, a facile and cost-effective approach to reduce alginate molecular weight in a highly controlled manner using serial autoclaving is presented. Increasing the number of autoclave cycles results in proportional reductions in intrinsic viscosity, hydrodynamic radius, and molecular weight of the polymer while maintaining its chemical composition. Hydrogels fabricated from mixtures of the autoclaved alginates exhibit tunable mechanical properties, with inclusion of lower molecular weight alginate leading to softer gels with faster stress relaxation behaviors. The method is demonstrated by establishing how viscoelastic relaxation affects the spreading of encapsulated fibroblasts and glioblastoma cells. Results establish repetitive autoclaving as an easily accessible technique to generate alginates with a range of molecular weights and to control the viscoelastic properties of alginate hydrogels, and demonstrate utility across applications in mechanobiology, tissue engineering, and regenerative medicine.
Corrigendum to “Evaluation of gelatin bloom strength on gelatin methacryloyl hydrogel properties” [J. Mech. Behav. Biomed. Mater. 154 (2024) 106509]
Corrigendum to “Evaluation of gelatin bloom strength on gelatin methacryloyl hydrogel properties” [J. Mech. Behav. Biomed. Mater. 154 (2024) 106509]
Evaluation of gelatin bloom strength on gelatin methacryloyl hydrogel properties
Evaluation of gelatin bloom strength on gelatin methacryloyl hydrogel properties
Gelatin methacryloyl (GelMA) hydrogels are widely used for a variety of tissue engineering applications. The properties of gelatin can affect the mechanical properties of gelatin gels; however, the role of gelatin properties such as bloom strength on GelMA hydrogels has not yet been explored. Bloom strength is a food industry standard for describing the quality of gelatin, where higher bloom strength is associated with higher gelatin molecular weight. Here, we evaluate the role of bloom strength on GelMA hydrogel mechanical properties. We determined that both bloom strength of gelatin and weight percent of GelMA influenced both stiffness and viscoelastic ratio; however, only bloom strength affected diffusivity, permeability, and pore size. With this library of GelMA hydrogels of varying properties, we then encapsulated Swan71 trophoblast spheroids in these hydrogel variants to assess how bloom strength affects trophoblast spheroid morphology. Overall, we observed a decreasing trend of spheroid area and Feret diameter as bloom strength increased. In identifying clear relationships between bloom strength, hydrogel mechanical properties, and trophoblast spheroid morphology, we demonstrate that bloom strength should considered when designing tissue engineered constructs.
Tumor Spheroid Fabrication and Encapsulation in Polyethylene Glycol Hydrogels for Studying Spheroid-Matrix Interactions
Tumor Spheroid Fabrication and Encapsulation in Polyethylene Glycol Hydrogels for Studying Spheroid-Matrix Interactions
Three-dimensional (3D) encapsulation of spheroids is crucial to adequately replicate the tumor microenvironment for optimal cell growth. Here, we designed an in vitro 3D glioblastoma model for spheroid encapsulation to mimic the tumor extracellular microenvironment. First, we formed square pyramidal microwell molds using polydimethylsiloxane. These microwell molds were then used to fabricate tumor spheroids with tightly controlled sizes from 50-500 μm. Once spheroids were formed, they were harvested and encapsulated in polyethylene glycol (PEG)-based hydrogels. PEG hydrogels are a versatile platform for spheroid encapsulation, as hydrogel properties such as stiffness, degradability, and cell adhesiveness can be tuned independently. Here, we used a representative soft (~8 kPa) hydrogel to encapsulate glioblastoma spheroids. Finally, a method to stain and image spheroids was developed to obtain high-quality images via confocal microscopy. Due to the dense spheroid core and relatively sparse periphery, imaging can be difficult, but using a clearing solution and confocal optical sectioning helps alleviate these imaging difficulties. In summary, we show a method to fabricate uniform spheroids, encapsulate them in PEG hydrogels and perform confocal microscopy on the encapsulated spheroids to study spheroid growth and various cell-matrix interactions.
Feature Reviews in Pharmaceutical Technology
Feature Reviews in Pharmaceutical Technology
We are excited to present the Special Issue, “Feature Reviews in Pharmaceutical Technology”, aiming to highlight exciting developments in pharmaceutical technologies […].