Date of Award
Winter 2025
Project Type
Dissertation
Program or Major
Chemical Engineering
Degree Name
Doctor of Philosophy
First Advisor
Linqing Li
Second Advisor
Nivedita Gupta
Third Advisor
Kyung Jae Jeong
Abstract
The compositional heterogeneity and structural diversity of native extracellular matrix are essential in regulating cell behavior and promoting tissue regeneration. Thermoresponsive polysaccharide-based materials with tunable phase transition temperatures and phase-separated microstructures offer substantial opportunities in tissue engineering, drug delivery, and wound healing applications. Here, we developed a new class of programmable dextran-based thermoresponsive polysaccharide condensates by chemically converting the hydrophilic homopolysaccharide dextran into hydrophobic derivatives. These materials exhibited reversible phase transitions and tunable lower critical solution temperatures that can be systematically modulated via variations in polysaccharides concentration, molecular weight, degree of methacrylation, ionic strengths and surfactants characteristics. Photo-initiated radical polymerization permits facile chemical crosslinking and kinetic capture of phase separation at different materials compositions, enabling the formation of hydrogels with tunable microstructures such as, core-shell structures, interconnected elongated micelles, vesicle-like structures, continuous phase, and dual emulsions. Different combinations of surfactant-polysaccharide matrices exhibited structurally coordinated adhesive and mechanical properties, with core-shell structures promoting reduced adhesion and elongated structures showing decreased modulus. The phase-separated heterogeneous dextran hydrogels also promoted enhanced interfacial-driven cell migration in 3D, with minimal cell migration in non-phase-separated homogeneous hydrogels. Hence, engineering macromolecular hydrophobicity with temperature-triggered phase separation of conventional hydrophilic, non-phase-separating polysaccharides to generate heterogeneous hydrogels with controlled microstructures will find potential applications in chronic wound healing, drug delivery, and enabling the design of biocomposite materials with tailored properties.
Recommended Citation
Bubli, Saniya Yesmin, "Leveraging Phase Separation to Engineer Biomaterial Microstructures and Regulate Cellular Behavior for Wound Healing Applications" (2025). Doctoral Dissertations. 2977.
https://scholars.unh.edu/dissertation/2977