Uto Koichiro, Muroya Takanari, Okamoto Michio, Tanaka Hiroyuki, Murase Tsuyoshi, Ebara Mitsuhiro, Aoyagi Takao
Biomaterials Unit, International Center for Materials Nanoarchitectonics (WPI-MANA), National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki, 305-0044, Japan.
Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Osaka, 565-0871, Japan.
Sci Technol Adv Mater. 2012 Nov 23;13(6):064207. doi: 10.1088/1468-6996/13/6/064207. eCollection 2012 Dec.
We newly designed super-elastic biodegradable scaffolds with longitudinally oriented microchannels for repair and regeneration of peripheral nerve defects. Four-armed poly(-caprolactone--D,L-lactide)s (P(CL--DLLA)s) were synthesized by ring-opening copolymerization of CL and DLLA from terminal hydroxyl groups of pentaerythritol, and acryloyl chloride was then reacted with the ends of the chains. The end-functionalized P(CL--DLLA) was crosslinked in a cylindrical mold in the presence of longitudinally oriented silica fibers as the templates, which were later dissolved by hydrofluoric acid. The elastic moduli of the crosslinked P(CL--DLLA)s were controlled between 10 and 10 MPa at 37 °C, depending on the composition. The scaffolds could be elongated to 700% of their original size without fracture or damage ('super-elasticity'). Scanning electron microscopy images revealed that well-defined and highly aligned multiple channels consistent with the mold design were produced in the scaffolds. Owing to their elastic nature, the microchannels in the scaffolds did not collapse when they were bent to 90°. To evaluate the effect of the channel diameter on Schwann cell migration, microchannels were also fabricated in transparent poly(dimethylsiloxane), allowing observation of cell migration. The migration speed increased with channel size, but the Young's modulus of the scaffold decreased as the channel diameter increased. These findings may serve as the basis for designing tissue-engineering scaffolds for nerve regeneration and investigating the effects of the geometrical and dimensional properties on axonal outgrowth.
我们新设计了具有纵向排列微通道的超弹性可生物降解支架,用于周围神经缺损的修复和再生。通过季戊四醇的端羟基对己内酯(CL)和丙交酯(DLLA)进行开环共聚合成了四臂聚(己内酯-丙交酯)(P(CL-DLLA)),然后使丙烯酰氯与链端反应。末端功能化的P(CL-DLLA)在纵向排列的二氧化硅纤维作为模板的情况下于圆柱形模具中交联,随后通过氢氟酸将模板溶解。交联后的P(CL-DLLA)的弹性模量在37℃下根据组成控制在10至10兆帕之间。这些支架可以伸长至其原始尺寸的700%而不发生断裂或损坏(“超弹性”)。扫描电子显微镜图像显示,支架中产生了与模具设计一致的明确且高度排列的多个通道。由于其弹性性质,支架中的微通道在弯曲至90°时不会塌陷。为了评估通道直径对雪旺细胞迁移的影响,还在透明聚二甲基硅氧烷中制造了微通道,以便观察细胞迁移。迁移速度随通道尺寸增加而提高,但支架的杨氏模量随着通道直径的增加而降低。这些发现可为设计用于神经再生的组织工程支架以及研究几何和尺寸特性对轴突生长的影响奠定基础。