Design of multi-functional hydrogel for cell therapies
Hydrogel;Cell Therapy;Methacrylic Alginate;Hydrophilic Pendant Chains;Decoupled Control;Stiffness;Permeability;Polyaspartamide Protein Linker;Biomineralization
Hydrogels are being actively investigated as encapsulation devices for cell transplantation therapies, as they provide structural stability and protection against harsh chemical and mechanical stimuli, and host immune system.In addition, chemical moieties, mechanical stiffness, and minerals presented in hydrogels act as insoluble signals to regulate a variety of cellular function.However, the conventional hydrogel design is plagued by complex dependencies between hydrogel properties; stiffness, permeability, density of cell adhesion molecules, and mineralization capacity.The objective of this research is to decouple or tune the intricate dependencies between these hydrogel properties, in order to better understand and regulate cellular activities in a 3D matrix.The hydrogel system is created by the assembly of three functional modules that contribute to the overall hydrogel properties: (1) The dependency between stiffness and permeability was tuned by incorporating pendant polymeric chains into a poly(ethylene glycol)-based hydrogel system; (2) Incorporation of alginate into a hydrogel system by co-polymerization allowed the control of hydrogel stiffness without affecting permeability; (3) The hydrogel was modified with cell adhesion proteins independent of other hydrogel properties using an amine-reactive polyaspartamide linker enabling single-step protein conjugation.Furthermore, mineralization capacity of the hydrogel was controlled independently by modulating hydrophobicity, charge density, and porosity.The efficacy of the hydrogel system developed in this research was evaluated by encapsulating two different cell types, fibroblasts and mesenchymal stem cells, and exploring the effects of hydrogel properties on the viability and growth factor expression of the encapsulated cells.
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Design of multi-functional hydrogel for cell therapies