Development of a Decellularized Hydrogel Composite and its Application in a Novel Model of Disc-associated Low Back Pain in Female Sprague Dawley Rats

Authors

David Lillyman, University of Nebraska-LincolnFollow

First Advisor

Rebecca A. Wachs

Date of this Version

Summer 7-29-2022

Document Type

Article

Citation

Lillyman, D.J. (2022). Development of a Decellularized Hydrogel Composite and its Application in a Novel Model of Disc-associated Low Back Pain in Female Sprague Dawley Rats. University of Nebraska - Lincoln.

Comments

A DISSERTATION Presented to the Faculty of The Graduate College at the University of Nebraska In Partial Fulfillment of Requirements For the Degree of Doctor of Philosophy, Major: Biomedical Engineering, Under the Supervision of Professor Rebecca Wachs. Lincoln, Nebraska: July, 2022

Copyright © 2022 David Lillyman

Abstract

Chronic low back pain is a global socioeconomic crisis compounded by an absence of reliable, curative treatments. The predominant pathology associated with chronic low back pain is degeneration of intervertebral discs in the lumbar spine. During degeneration, nerves can sprout into the intervertebral disc tissue and be chronically subjected to inflammatory and mechanical stimuli, resulting in pain. Pain arising from the intervertebral disc, or disc-associated pain, is a complex, multi-faceted disorder which necessitates valid animal models to screen therapeutics and study pathomechanisms of pain.

While many research teams have created animal models of disc degeneration, the translation of these platforms to disc-associated pain models has been limited by an absence of chronic pain-like behavior. Further, the few models which measure disc-associated pain-like phenotypes have been established in mice, which are not amenable to surgical treatment procedures due to their small size. This deficiency drives the need for a new model of disc-associated pain where pain-like behavior is measurable and intervertebral discs are large enough for surgical procedures. These criteria promote rats as the optimal platform for a disc-associated model of chronic low back pain.

Herein, a rat model of disc-associated pain is described that displays chronic pain-like behavior, overt disc degeneration, and nerve sprouting in the intervertebral disc. In addition to the model, a novel method for measuring disc degeneration real-time, non-invasively, is delineated which exhibits remarkable precision and accuracy. Finally, a next generation treatment, derived from decellularized, porcine nucleus pulposus tissue is described which is injectable, thermally fibrillogenic, and cytocompatible. In the rat model of disc-associated pain, this biomaterial restores degenerated disc volume and dramatically decreases pain-like behavior.

In summary, this dissertation describes the development of a method for quantifying degeneration real-time, establishes a rat model of disc-associated pain, and successfully treats disc-associated pain in this model with a next-generation biomaterial.

Advisor: Rebecca Wachs