Abstract
摘要:神經導管(Nerve conduits or nerve guidance channels)之功能在接合受損或斷裂的周
邊神經,使其於導管內再生;目前臨床上的瓶頸為中間隙(1 cm 以上)神經缺損的再生。
本研究計畫擬針對本團隊最近幾年來發展設計出的一系列可分解新穎神經導管,進行臨
床前開發與轉譯研究,以使此創新醫療器材產品能在未來進行臨床驗證,並順利上市而
實際應用於臨床神經的修復。本團隊之新穎神經導管依照不同的設計與加值而發展出第
一代(中間隙神經缺損)與含生長因子(大間隙神經缺損)的神經導管。第一代神經導管具
有特殊非對稱孔洞及微溝槽結構(擁有一個專利),含生長因子的神經導管為第一代導管
表面改質並含入生長因子FGF1 (擁有一個專利與兩個專利申請中)。第一年計畫已完成
導管製程改良,以符合未來量產之需求,並已開始小量試產GMP 製程之第一代導管。
動物實驗已完成第一階段大鼠第一代導管實驗及市售導管比對實驗,並建構大鼠電生理
測試平台;在兔25 mm 神經間隙修復模式方面,則已分別進行第一代導管及含生長因
子導管實驗。第二年計畫將持續進行導管GMP 製程生產及量產化製程改良,確認導管
之再現性,並以改良製程與GMP 生產及滅菌後的神經導管進行動物實驗,建構兔電生
理測試平台,並進行大型實驗動物李宋猪實驗。本團隊開發之神經導管製程簡單,且目
前基礎專利佈局已接近完成,期望經由本計畫研究成果獲得應用專利佈局策略,為未來
產品上市作更嚴謹保護。本計畫擬結合跨領域執行團隊,經由本計畫的推動,達到神經
導管臨床前開發與轉譯的目標。計畫中依據大鼠、兔及猪之動物實驗模式依序進行轉譯
工作,同時規劃以完整的動物實驗數據申請使用GMP 製程製作之導管進行臨床試驗,
最終使神經導管通過上市申請,並順利行銷,以達到醫療器材在地化、培育生技產業之
關鍵技術人力、扶植本土生技產業進行高附加價值醫療器材生產以及臨床神經修復等目
的。
Abstract: Nerve conduits (or nerve guidance channels) are used to bridge the injured or transected
nerve fibers. The current challenge is to repair the wider gap defect (> 1 cm). This project
is to fabricate novel biodegradable nerve conduits developed from our team and perform the
preclinical translational research to facilitate the implementation to the future clinical trials.
The novel nerve conduits include the product design of two generations. The first
generation conduits are microporous/microgrooved poly(D,L-lactide) conduits for
regeneration of medium nerve gap defects (granted one patent). The conduits with growth
factors are those grafted with FGF1 for repairing large nerve gap defects (one patent granted
and two patents pending). The developed conduits have the advantage of convenient
manufacturing processes. The layout of basic patents is almost finished. In the first year of
the project, the fabrication procedures have been modified to meet the needs of mass
production. The conduits have been manufactured by GMP processes. In animal
experiments, the first generation conduits have been compared with the commercial nerve
conduits in rats. The platform for electrophysiological testing in rats has also been
established. The first generation conduits and those grafted with FGF1 have been implanted
in rabbits. In the following year, conduits will be continued made by modified procedures
and GMP processes. The reproducibility of physico-chemical properties of GMP conduits
will be confirmed. The GMP/sterilized conduits will be used in all animal studies. The
performance of conduits will be further evaluated in Lee-Sung pigs. We expect that this
project can help the layout of more application-oriented patents that should provide full
protection of intellectual rights to our products. This project integrates active researchers
from different areas and is truly interdisciplinary. After translation from rats and rabbits to
pigs, we plan to apply clinical trials based on GMP manufactured conduits. Eventually,
these products can be accredited, approved by the regulating authorities and be successfully
marketed. This project can provide an opportunity for commercialization of a new medical
device from Taiwan, train the key technical manpower, and support the medical device
industry to produce high value-added medical devices for clinical use.
Keyword(s)
神
經導管
周邊神
經
醫療
器材
動物實驗
臨
床試驗
keyword:Nerve conduits
peripheral nerve
medical devices
animal study
clinical trial