乙基纖維素強化之聚己內酯神經導管內部固定Interlukin-12p80及混入磁性粒子用於周邊神經再生 導管之研究

Abstract

神經導管修復（Nerve guidance conduit repair ,NGC repair） 雖然並不是目前治療周圍神經損傷的最佳首選，但為了改善其他周圍神經修補的缺點，因此神經導管修補這個技術的開發是個很重要的研究方向，也作為本實驗用以治療周圍神經損傷的修復方法。在目前大多數的研究中，將神經成長因子固定於導管內壁，並且期望能夠提升神經再生的效果，但結果卻往往差強人意，原因是在周邊神經損傷的再生中扮演最重要的腳色的是許旺細胞這類型的支持細胞，這個細胞也是構成髓鞘之的原料。因此在大多的研究中往往只能讓軸突進行再生，但最重要的髓鞘卻常常難以再現。 在本實驗中選用乙基纖維素強化之聚己內酯（Poly(ε-caprolactone) blended with cellulose, PCLC）作為導管材料，除此之外，在導管內固定上Interlukin-12p80，期望能將病患體內的原生神經幹細胞誘導分化為許旺細胞類的支持細胞，藉此讓周圍神經的再生效果更佳。而在導管內部混上磁性粒子，並藉由變化磁場之作用讓導管產生熱能，藉此運用熱療來修復神經。在本實驗中運用熱療及Interlukin-12p80的共同作用來促使周圍神經之再生。 經由SEM影像顯示，經過本論文之製成後能夠有效的合成出來具有內層大孔洞外層小孔洞之目標導管結構。經WST-1檢驗，其結果符合ISO10993之規範，證明該材料具有良好生物相容性。在體驗試驗的結果中，我們證實了熱效應確實對於神經軸突之生長有促進之效果。動物實驗的部分，藉由實驗結果顯示，導管在經由磁場刺激作用之後依然能夠有良好的升溫效果。

Although Nerve guidance conduits repair is not the best choice for peripheral nerve repair, for improving the shortcomings of other peripheral nerve repair methods, this method is the most important technique in the peripheral nerve repair. Therefore, we use nerve guidance conduits repair to cure peripheral nerve injury. In most of the current research, the neural growth factor is fixed to the inner wall of the conduit, and expect to be able to enhance the nerve regeneration , but the results are often disappointing. The reason is that in the peripheral nerve injury regeneration, Schwann cell play an important role in peripheral nerve regeneration which is a type of supporting cell, this cell also constitute the myelin sheath. In our experiment, we use ethyl cellulose to reinforce polycaprolactone as nerve conduit. Otherwise, we will immobilize Interlukin-12p80 on the inner side of the nerve conduit and expect that Interlukin-12p80 can direct neuron stem cells, which are found near the regeneration site, to differentiate toward supporting cell such as Schwann cell. And in the conduit, we will blend with Fe3O4 for generating heat with the pulsed magnetic field. Owing to the cooperation of the heat treatment, pulsed magnetic field and Interlukin-12p80, we can expect that there will have good results in peripheral nerve regeneration. The SEM image show that we successfully fabricated porous PCLC conduits with big pore inside and small pore outside of the conduit. in the WST-1 test results, the experiment follow the specification of ISO-10993, PCLC shown to be biocompatible. Through the result of in vitro test, we know that heat treatment indeed can promote neurite outgrowth. In the part of animal study, result shows that conduit still have good warming ability after stimulated by magnetic field.