Date of Award

5-2024

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Bioengineering

Committee Chair/Advisor

Jeremy Mercuri, Ph.D.

Committee Member

Sanjitpal Gill, M.D.

Committee Member

Yongren Wu, Ph.D.

Committee Member

Dan Simionescu, Ph.D.

Abstract

Intervertebral disc degeneration (IVDD) is a prominent pathology in the modern world that causes debilitating pain for many patients. The onset of IVDD occurs in the nucleus pulposus (NP). NP biomaterials will play a vital role in mitigating the progression of IVDD. Within this work, we sought to synthesize a solubilized extracellular matrix (ECM)-based NP biomaterial. Utilizing pepsin or urea extraction, bovine NP ECM was successfully solubilized (SBNPs). SBNP formulations were characterized biochemically, evaluated for cytotoxicity, and down-selected for front-running formulations. Leading candidate SBNPs were incorporated into an alginate bead biomaterial model to determine the potential bioactivity with human adipose-derived mesenchymal stromal cells (hAD-MSCs). Results showed that SBNP synthesized with urea extraction resulted in significantly higher retention of glycosaminoglycans.

Translation of NP biomaterials requires animal model validation. Large animal models to conduct these pivotal studies can be burdensome. This is particularly due to the cost and availability of longitudinal, high-field magnetic resonance imaging. (hf-MRI) of IVDs which have become a standard outcome measure. Therefore, we sought to establish a caprine model of IVDD using a more accessible imaging modality, low-field MRI (lf-MRI), which, once validated, could be utilized for assessing the efficacy of NP biomaterials in development. Our research demonstrated that lf-MRI systems may be capable of longitudinally tracking the progression of IVDD in a caprine model.

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