Itoh Soichiro, Yamaguchi Isamu, Suzuki Masumi, Ichinose Shizuko, Takakuda Kazuo, Kobayashi Hisatoshi, Shinomiya Kenichi, Tanaka Junzo
Division of Molecular Tissue Engineering, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo, Tokyo 113-8519, Japan.
Brain Res. 2003 Dec 12;993(1-2):111-23. doi: 10.1016/j.brainres.2003.09.003.
On the inner surface of tendon chitosan tubes having a triangular shape and a hydroxyapatite coating (t-chitosan/HAp tube), laminin-1 and laminin peptides (YIGSR, IKVAV) have been adsorbed in order to develop nerve growth conduits. The mechanical property, biocompatibility and efficacy of these tubes for nerve regeneration were examined. Step-1: bridge grafting (15 mm) into the sciatic nerve of Sprague-Dawley (SD) rats was carried out using either t-chitosan or t-chitosan/HAp tubes having either a circular or triangular cross section (N=12 in each group). Specimens were taken after 2-, 4-, 6- and 8-week post-implantation (N=3 in each group) for histology determinations. Step-2: t-chitosan/HAp tubes having a triangular cross section with adsorbed laminin-1, CDPGYIGSR or CSRARKQAASIKVAVSAD, as well as control tubes without pre-adsorption were used for implantation (N=18 in each group). Isografting was also carried out (N=6). Histological evaluation was carried out similarly as in Step-1. Furthermore, evoked muscle and sensory nerve action potentials were recorded, and the percentage of myelinated axon area measured at 10 mm distance of the distal anastomosed site in the experimental, control and isograft groups after 12 weeks (N=6 in each group). The results of histological findings, as well as mechanical properties, suggest that a triangular tube shape with a HAp coating benefits nerve regeneration. The effect of laminin peptides (YIGSR, followed by IKVAV) to enhance the growth of regenerating axons has been found comparable with intact laminin-1. Although histological regeneration in both the YIGSR- and laminin-1-treated t-chitosan/HAp tubes matches the isografts, the functional recovery is however delayed.
为了开发神经生长导管,在具有三角形形状且带有羟基磷灰石涂层的肌腱壳聚糖管(t-壳聚糖/羟基磷灰石管)的内表面吸附了层粘连蛋白-1和层粘连蛋白肽(YIGSR、IKVAV)。对这些导管用于神经再生的力学性能、生物相容性和功效进行了研究。步骤1:使用具有圆形或三角形横截面的t-壳聚糖管或t-壳聚糖/羟基磷灰石管,对Sprague-Dawley(SD)大鼠的坐骨神经进行15毫米的桥接移植(每组N = 12)。在植入后2周、4周、6周和8周取样(每组N = 3)进行组织学测定。步骤2:使用具有三角形横截面且吸附了层粘连蛋白-1、CDPGYIGSR或CSRARKQAASIKVAVSAD的t-壳聚糖/羟基磷灰石管以及未进行预吸附的对照管进行植入(每组N = 18)。还进行了同基因移植(N = 6)。组织学评估与步骤1类似。此外,记录诱发的肌肉和感觉神经动作电位,并在12周后测量实验、对照和同基因移植组中距远端吻合部位10毫米处有髓轴突面积的百分比(每组N = 6)。组织学结果以及力学性能表明,带有羟基磷灰石涂层的三角形管形状有利于神经再生。已发现层粘连蛋白肽(先为YIGSR,后为IKVAV)促进再生轴突生长的效果与完整的层粘连蛋白-1相当。尽管在YIGSR处理的和层粘连蛋白-1处理的t-壳聚糖/羟基磷灰石管中的组织学再生与同基因移植匹配,但功能恢复却延迟了。