Date of Award

2019

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Mechanical Engineering

First Advisor

Yves Dubief

Abstract

Injectable hydrogels are important for use in tissue engineering due to their permeability and biocompatibility. Those that have shear thinning properties allow for minimally-invasive surgical procedures and a way to administer bioactive agents, and therapeutic cells by injection. Currently available injectable hydrogels have a single or dual input/stimulus for crosslinking which limits the range of mechanical properties and often utilize potentially toxic ultraviolet radiation that reduces viability of injected cells. To overcome these shortcomings, a tri-stimuli-responsive alginate-based injectable hydrogel was developed based on: 1) supramolecular complex formation between β-cyclodextrin (β-CD) conjugated alginate and thermo-responsive tri-block Pluronic® copolymers, 2) visible light crosslinking via acrylate conjugation, and 3) ionic crosslinking of the alginate backbone via exposure to calcium chloride.

The capabilities of the novel multi-stimuli injectable hydrogel were demonstrated with a custom microfluidic devices (MFDs) to create microspheres encapsulating human mesenchymal stem cell (MSCs). These experiments proved that the new hydrogel was capable of serving as a stimuli responsive material for MSC cell delivery in the therapeutic range of 10-1000 µm in diameter. In order to enhance the drug delivery capabilities of the hydrogel, heparin sodium was conjugated onto the alginate backbone. The affinity of the growth factor, vascular endothelial growth factor (VEGF), to the heparin helped to prevent denaturing of the protein and improved vascularization. This new tri-crosslinking hydrogel with conjugated heparin allows the end-user to control the final physicomechanical and biochemical properties of the hydrogel using different external stimuli. The tri-crosslinking hydrogel is a versatile material that has great promise for a variety of soft tissue repair applications.

Language

en

Number of Pages

151 p.

Available for download on Thursday, November 26, 2020

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