Graduation Date

Fall 8-8-2023

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Programs

Medical Sciences Interdepartmental Area

First Advisor

Bin Duan

Second Advisor

Anna Dunaevsky

Third Advisor

Hanjun Wang

Fourth Advisor

Siwei Zhao

Abstract

Peripheral nerve injury (PNI) is a common problem worldwide, with trauma being a common cause. PNI can lead to loss of sensory and motor functions, chronic neuropathic pain, and mental health issues, significantly impacting patients' family life, work, and social situation. Recent studies revealed that beyond the topical injury site at peripheral nerves, PNIs can also induce dysfunctions in the central nervous system (CNS) by causing maladaptive plasticity, which will result in exaggeration and exacerbation of the pathological condition caused by primary injuries. The common therapy strategies for PNI treatment are using sutures, nerve autografts or conduits in cases requiring surgical intervention as well as applying physical-based rehabilitation to facilitate functional recovery. However, restoration of functions is generally unsatisfactory due to the insufficient regeneration and long-lasting neuroplasticity in the nervous system. Therefore, in the last two decades, various neurotrophic factors and neuroprotective agents have been extensively studied as an adjuvant therapy to enhance recovery efficiency after PNIs. Moreover, along with the prosperous development of biomaterial and bioengineering science, controllable drug delivery techniques have exhibited great potential in maintaining drugs’ bioactivity and thus prolonging the therapeutic functions. In this project, we first investigated neuroplastic changes in the nervous system, particularly in the spinal cord and supraspinal regions, during the treadmill rehabilitation after a long-gap nerve defect and autograft implantation. Moreover, we further developed a versatile hydrogel-based drug delivery system that can effectively treat both acute and chronic PNIs. Our study reveals that treadmill exercise could further modulate PNI-related neuroplasticity, potentially influencing an individual’s cognition and perception of the injury. In addition, the hydrogel was orthotopically injected to the injured nerves and sustainedly released encapsulated therapeutic cargos, thereby promoting nerve regeneration, relieving pain, and facilitating functional recovery. In summary, the thesis project provides deeper insights of PNIs and recovery by exercise rehabilitation in terms of central neuroplastic changes. In addition, the multifunction hydrogel can spatially and temporally control neuro-supportive and -protective agents, thus showing promising medical application to benefit patients suffering from PNIs.

Comments

2023 Copyright, the authors

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