Graduation Semester and Year

2013

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Biomedical Engineering

Department

Bioengineering

First Advisor

Jonathan Cheng

Abstract

Peripheral nerve injuries that arise as a result of trauma, tumor excision or birth can adversely affect the quality of patient life, leading to lifelong disabilities in some cases. Autologous nerve grafts are the clinical "gold standard" for long gap nerve repair, and allogeneic nerve grafts are considered the next best treatment option. Despite having numerous benefits, autologous nerve grafts are associated with limited supply, longer operation time, risk of infection, painful neuroma formation and most importantly, loss of function at the donor site. Allogeneic nerve grafts require transient immunosuppression, which exposes the patients to risks of infection, toxicity and possible malignancy. To overcome the limitations of current treatment procedures, use of decellularized nerve grafts has been developed as an alternative treatment strategy. The aim of this research is to develop detergent-free decellularized nerve grafts for repair of long gap peripheral nerve defects. We first developed a detergent-free decellularization technique for producing nerve grafts with appropriate mechanical, structural and biological properties. These decellularized nerve grafts were tested for functional nerve regeneration at multiple time points with and without exogenous cells in the grafts across a 35 mm long gap defect. Finally, we compared the detergent-free decellularized nerve grafts with a well-established detergent processing method, and found that the detergent-free decellularized nerve grafts without any additional factors was sufficient to promote functional nerve regeneration. To understand the molecular differences between a regenerative and a non-regenerative nerve injury, we developed a growth vs. no-growth injury model. Difference in histological and molecular profile between the two injuries indicated a difference in response to injury and repair. Data from this work enabled us to select compounds which could potentially be used for improving nerve regeneration. Finally, we found that the compounds selected from molecular profiling promoted peripheral nerve regeneration. We optimized the detergent-free decellularization process and examined nerve regeneration with and without addition of exogenous compounds. The in vivo results suggest that the improved decellularized nerve grafts along with exogenous delivery of compound was significantly better than the initially developed decellularized grafts, and regeneration was comparable to unprocessed (fresh) nerve graft. There is a potential for clinical translation of these promising results to improve the lives of patients with nerve injuries.

Disciplines

Biomedical Engineering and Bioengineering | Engineering

Comments

Degree granted by The University of Texas at Arlington

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