Document Type

Dissertation

Date of Award

5-31-2019

Degree Name

Doctor of Philosophy in Chemical Engineering - (Ph.D.)

Department

Chemical and Materials Engineering

First Advisor

Xiaoyang Xu

Second Advisor

Rajesh N. Dave

Third Advisor

Xianqin Wang

Fourth Advisor

Murat Guvendiren

Fifth Advisor

Peng Jiang

Abstract

Hydrogels were first discovered in the year 1960 by Wichterle and Lim [1], and in the following decades, they have been widely studied because of their unique characteristics including their hydrophilic nature, biocompatibility, and capacity to mimic the extracellular matrix (ECM). Hydrogels based on natural or synthetic polymers have continued to be of interest for tissue engineering and drug delivery due to their ability to encapsulate living cells and control the release rate of drugs or other bioactive molecules such as pharmaceutical proteins.

In the first part of this dissertation, dopant-free photoluminescent hydrogels formed in situ by crosslinking of biocompatible polymer precursors are developed. The results demonstrate that the newly developed hydrogels possess tunable degradation, intrinsic photoluminescence, mechanical properties, and exhibit sustained release of various molecular weight dextrans. In vivo studies show that the hydrogels formed in situ following subcutaneous injection exhibit excellent biocompatibility and emit strong fluorescence under visible light excitation without the need of using any traditional organic dyes. Their in vivo degradation profiles are then depicted by non-invasively monitoring fluorescence intensity of the injected hydrogel implants.

Next, Myeloid Derived Growth Factor (Mydgf) is incorporated with the hydrogel for cardiac recovery and its efficacy is investigated as a post-Myocardial infarction (MI) therapy. Intramyocardial injection of the Mydgf-loaded hydrogel is shown to significantly reduce scar formation and infarct size, increase wall thickness and neovascularization, and improve heart function and survival in a rat MI model. Furthermore, the controlled-release hydrogel attenuates cardiomyocyte apoptosis and increased microvessel density in the infarcted hearts, leading to sustained beneficial effects on cardiac functional and morphological recovery.

Finally, a one step, green chemistry, biocompatible Poly vinyl alcohol (PVA) based hydrogel formed in situ by Thiol-Acrylate Michael Addition is presented. Results demonstrate that the newly developed hydrogels not only possess tunable degradation, mechanical and release profiles but also 3D printable and exhibit superior-biocompatible properties for stem cell culture both in 2D and 3D. More importantly, in vivo studies show that the hydrogels formed in situ following subcutaneous injection exhibit excellent biocompatibility.

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