Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 330-714, Republic of Korea.
Department of Biotechnology, Yonsei University, Seoul, 120-749, Republic of Korea.
Macromol Biosci. 2018 Dec;18(12):e1800290. doi: 10.1002/mabi.201800290. Epub 2018 Nov 8.
An innovative technique combining capillary force lithography and phase separation method in one step is applied to fabricate artificial nerve guidance conduit (NGC) for peripheral nerve regeneration. Biodegradable porous, patterned NGC (PP-NGC) using poly(lactic-co-glycolic acid) is fabricated. It has micro-grooves and microporosity on the inner surface to promote axonal outgrowth and to enhance permeability for nutrient exchange. In this study, it is confirmed that the inner surface of micro-grooves can modulate neurite orientation and length of mouse neural stem cell compared to porous flat NGC (PF-NGC) in vitro. Coating with 3,4-dihydroxy-l-phenylalanine (DOPA) facilitates the hydrophilic inner surface of PF- and PP-NGCs via bioinspired catechol chemistry. For in vivo study, PF-NGC and PP-NGC coated with or without DOPA are implanted in the 10 mm sciatic nerve defect margins between proximal and distal nerves in rats. Especially, PP-NGC coated with DOPA shows higher sciatic function index score, onset-to-peak amplitude, and muscle fiber diameter compared to other groups. The proposed hybrid-structured NGC not only can serve as a design for functional NGC without growth factor but also can be used in clinical application for peripheral nerve regeneration.
一种结合了毛细作用力光刻和相分离方法的创新技术被应用于制造用于周围神经再生的人工神经引导导管(NGC)。使用聚(乳酸-共-乙醇酸)制造了可生物降解的多孔、图案化 NGC(PP-NGC)。它在内表面上具有微槽和微孔,以促进轴突生长并增强营养物质交换的渗透性。在这项研究中,与多孔平 NGC(PF-NGC)相比,确认了微槽的内表面可以在体外调节鼠神经干细胞的突起取向和长度。通过生物启发的儿茶酚化学,用 3,4-二羟基-l-苯丙氨酸(DOPA)涂覆可以使 PF-NGC 和 PP-NGC 的亲水内表面变得容易。在体内研究中,将涂覆有或不涂覆 DOPA 的 PF-NGC 和 PP-NGC 植入大鼠近端和远端神经之间的 10mm 坐骨神经缺损边缘。特别是,涂覆有 DOPA 的 PP-NGC 与其他组相比,具有更高的坐骨功能指数评分、潜伏期至峰值幅度和肌纤维直径。所提出的混合结构 NGC 不仅可以作为无生长因子的功能性 NGC 的设计,还可以用于周围神经再生的临床应用。