Flexible Nerve Guidance Conduit for Peripheral Nerve Regeneration

This dissertation, "Flexible Nerve Guidance Conduit for Peripheral Nerve Regeneration" by Wai-man, Choy, 蔡維敏, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: The golden method of peripheral nerve system injury is the nerve autograft, but it is associated with drawbacks such as donor site morbidity, needs of second incisions and the shortage of nerve grafts. Comparatively, connecting the nerve defect directly is an alternative. Unfortunately, if the defects are long, the induced tension will deteriorate the nerve regeneration. These limitations led to the development of artificial nerve guidance conduit (NGC). The market available NGC have problems of unsatisfactory functional recovery and may collapse after the implantation. These are attributed to material and structural deficiencies. Therefore, there is essential to study a biomaterial, which has excellent biological and physical properties to fit the NGC application. In addition, some studies suggested that the poor functional recovery resulted from the NGC implantation were due to the lack of micro-guidance inside the conduit. Thus, it is necessary to investigate the structural influence on the functional recovery of peripheral nerve injury. Crosslinked urethane-doped polyester elastomer (CUPE) is newly invented for a blood vessel graft because it possesses similar mechanical properties of blood vessel which is similar to nerve as well. Therefore, CUPE was also considered to be the NGC. Its biocompatibility has been proved to be excellent in the previous study done by Dr. Andrew SL, Ip. Targeting on the long peripheral nerve regeneration, the aims of this study are (1) to investigate the biocompatibility of CUPE in in-vitro condition and (2) to study the influence of nerve-like structure on the peripheral nerve system injury in an animal model. The ultimate goal is to enhance the functional recovery of peripheral nerve system injury by implanting a flexible biomaterial, CUPE, which has a nerve-like microarchitecture. It is hypothesized that the nerve-like structure can promote the axonal regeneration. The surface energy and roughness of CUPE were investigated. It showed a relatively low surface energy compared to other conventional biopolymers such that the cell adhesion and also the proliferation were inhibited. Therefore, the CUPE was modified by the immersion into a high glucose DMEM. The change in the hydrophilicity, roughness and cell viability of medium treated CUPE were studied. The hydrophilicity of treated CUPE was increased but the roughness was remaining unchanged whereas the pH of the immersion solution did not cause any effect on the cell activity on the CUPE. In the pilot animal study, five channels along the CUPE-NGC had a similar myelinated fiber density and population compared to the nerve autograft. Also, the channels in the CUPE-NGC were fragmented. In summary, the medium treatment could enhance the hydrophilicity of CUPE and the cell activity on CUPE. Such modifications did not governed by the pH of the medium. The NGC-CUPE with five channels, which imitated a basic nerve structure was shown to have a similar tissue regeneration and the functional recovery as the nerve autograft did. The results proved the hypothesis that the nerve-like structure can promote the functional recovery of peripheral nerve system injury with the use of a new biomater