ORCID ID
Graduation Date
Spring 5-7-2026
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Programs
Interdisciplinary Graduate Program in Biomedical Sciences
First Advisor
Dr. Bin Duan
Abstract
Peripheral nerve injury (PNI), particularly following trauma, predominantly affects the working-age population, translating to substantial socioeconomic as well as clinical consequences. Following nerve injury, target muscles become denervated and progressively undergo atrophy due to loss of neural signals, leading to functional decline and reduced quality of life. Although most therapeutic strategies for PNI focus primarily on promoting nerve regeneration, the accompanying muscle atrophy is often ignored, which limits overall functional recovery. These challenges are especially pronounced in long-gap PNI, which is commonly treated with nerve grafts. Autologous nerve grafting remains the gold standard for repairing long-gap defects. However, its use is limited by donor-site morbidity and graft availability. Alternative strategies, including decellularized nerve grafts (DNGs) and engineered nerve conduits, have shown some success in defects less than 15 mm but have been ineffective for longer defects. This might be because their microenvironments are suboptimal to support cellular infiltration, proliferation, vascularization, and axonal growth. In parallel, electrical stimulation (EStim) is used to maintain denervated muscle pending reinnervation. However, effective stimulation of denervated muscle requires high current intensities that can cause tissue injury when delivered through conventional electrodes. To address these dual challenges, this thesis developed two complementary therapeutic strategies. First, we engineered a porous decellularized nerve graft (PDNG) with an optimal microenvironment to support cellular infiltration, proliferation, and axonal growth. Second, we developed, validated, and applied a hydrogel ionic circuit (HIC) system capable of delivering high-intensity EStim without causing tissue damage. Our findings demonstrated that PDNG promoted Schwann cell proliferation for myelination and enhanced endothelial cell infiltration for graft vascularization. On the other hand, the HIC system safely delivered 32 mA stimulation without tissue injury, promoted myoblast differentiation into myotubes, increased growth factor production, and preserved denervated skeletal muscle. Overall, this thesis establishes PDNG as a promising regenerative scaffold for peripheral nerve repair and as a potential platform for future therapeutic and living-cell loading applications. It further demonstrates that the HIC EStim system is a promising strategy for preserving denervated muscle during the prolonged period required for nerve regeneration. Together, these approaches address both nerve repair and muscle preservation, which are two critical determinants of functional recovery following PNI.
Rights
The author holds the copyright to this work and any reuse or permissions must be obtained from the author directly.
Recommended Citation
Alimi, Olawale, "Engineering Approaches to Promote Peripheral Nerve Injury and Denervated Muscle Regeneration" (2026). Theses & Dissertations. 1060.
https://digitalcommons.unmc.edu/etd/1060
Included in
Bioelectrical and Neuroengineering Commons, Biomedical Devices and Instrumentation Commons, Molecular and Cellular Neuroscience Commons, Molecular, Cellular, and Tissue Engineering Commons, Musculoskeletal Diseases Commons, Musculoskeletal, Neural, and Ocular Physiology Commons, Musculoskeletal System Commons, Nervous System Commons, Neurosciences Commons, Translational Medical Research Commons