Flexible nerve guidance conduit for peripheral nerve regeneration

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 biomaterial, CUPE as the NGC substrate.