Behun, Marissa N.
(2024)
Investigating the Effects of Porcine-Derived Peripheral Nerve Matrix Hydrogel on Neuromuscular Function Following Direct Muscle Neurotization.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Peripheral nerve injuries (PNI) impact over twenty million Americans and occur at an incidence rate of 600,000 new PNIs per year. While surgical and biomaterial options are available for clinical treatments of crush and gap nerve injuries, there is a lack of available treatments for nerve injuries that lack a pre-existing nerve-muscle pedicle. Reinnervation of a muscle in the absence of a viable nerve stump following a traumatic injury poses a difficult clinical challenge. Direct muscle neurotization (DMN) provides an approach to overcome this obstacle. Previous animal studies and case reports in humans have shown promise in reinnervation using DMN; however, this success is dependent upon the formation of neuromuscular junctions and endplates, which can be difficult to regenerate without appropriate axonal pathway cues. Previous studies have shown that implementation of an extracellular matrix derived biomaterial can help drive regeneration. Specifically, use of a peripheral nerve-derived extracellular matrix (PNM) product can promote functional recovery, axonal outgrowth and increase NMJ formation in multiple neuromuscular regeneration applications. This dissertation focuses on investigating the use of DMN coupled with PNM. Aim 1 shows an 132% increase in functional outcomes when DMN is coupled with PNM and an improvement of NMJ formation at earlier timepoints. To determine the feasibility of terminal sterilization of PNM (a requirement for eventual clinical translation), the PNM was treated E-beam irradiation. No differences were found in functional or histologic outcomes between the terminally sterilized and non-sterilized; however, there were differences in the number of muscle fibers present in animals treated with sterile PNM following DMN. This was corroborated with an improved electrophysiologic response in animals treated with sterile PNM versus non-sterile PNM. Aim 3 found that Schwann exposed to eluted PNM products show a de-differentiated phenotype, and that Schwann cells in direct contact with PNM exhibit a re-differentiated phenotype. These findings show that the way in which the native cells interact with the PNM could have a greater impact than the reconstitution solution properties on the regenerative outcomes.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
6 September 2024 |
| Date Type: |
Publication |
| Defense Date: |
8 July 2024 |
| Approval Date: |
6 September 2024 |
| Submission Date: |
25 July 2024 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
156 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Swanson School of Engineering > Bioengineering |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Peripheral nerve injury, direct muscle neurotization, hydrogel, extracellular matrix |
| Date Deposited: |
06 Sep 2024 20:05 |
| Last Modified: |
06 Sep 2024 20:05 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/46743 |
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