Andrew Jones
BME MS Thesis Defense Presentation
Date: 2026-05-08
Time: 11:00 AM EST
Location / Meeting Link: https://teams.microsoft.com/meet/222902791704104?p=pBonO7gv236uStPLFI

Committee Members:
Dr. Svenja Illien-Junger ; Dr. Johnna Temenoff ; Dr. Jay Patel ; Dr. Rudolph Gleason


Title: Evaluation of a Polyethylene Glycol-Based Hydrogel Drug Delivery System on Murine Intervertebral Degeneration

Abstract:
Low back pain is prevalent in most generations globally, and much of this pain can be attributed to intervertebral disc (IVD) degeneration. The IVD consists of two distinct structures, the nucleus pulposus (NP) and annulus fibrosus (AF), which lose mechanical integrity as a result of IVD degeneration. Hydrogels are a prominent approach for NP replacement and drug delivery in IVD tissue repair and beyond. We previously showed the inhibition of PH domain leucine-rich protein phosphatase (PHLPP) promoted IVD health. As such, this project proposed a polyethylene glycol (PEG)-based hydrogel that polymerized through copper-free click chemistry combined with a small molecule PHLPP inhibitor conjugated to a chitosan nanocarrier to act as both a physical stabilizer in the IVD space as well as a means of halting IVD degeneration. Testing was first performed ex vivo with murine caudal IVDs to compare the mechanical restoration of different hydrogel combinations following a needle puncture injury. Testing identified the 4% PEG hydrogel successfully restored tensile stiffness following implantation and was chosen for all following studies. 4% PEG hydrogels with and without inhibitor were then injected in vivo into murine caudal IVDs following a needle puncture injury. Mice were sacrificed after 28 days and IVDs were harvested for mechanical and histological evaluation. Mechanical testing revealed that the 4% PEG hydrogel was capable of restoring multiple mechanical properties including axial range of motion, torque range, and mimicked overall IVD behavior in compressive, tensile, and torsional loading. Histological analysis revealed the 4% PEG+inhibitor hydrogel stayed in the IVD space of all implanted samples, retained the native IVD morphology following implantation, and reduced apoptosis in both the NP and AF. The 4% PEG and 4% PEG+inhibitor hydrogels were also tested in vitro for NP cell viability and were found to be non-cytotoxic with the elution profile of the PHLPP inhibitor in the order of weeks. These findings indicate that a hydrogel capable of redistributing loading forces across the entire IVD while delivering an effective degeneration inhibitor is a potential solution to mitigate future IVD degeneration, thus minimizing low back pain caused by IVD degeneration.