Noncovalent Bonding of RGD and YIGSR to an Electrospun Poly(epsilon-Caprolactone) Conduit through Peptide Self-Assembly to Synergistically Promote Sciatic Nerve Regeneration in Rats
Noncovalent Bonding of RGD and YIGSR to an Electrospun Poly(epsilon-Caprolactone) Conduit through Peptide Self-Assembly to Synergistically Promote Sciatic Nerve Regeneration in Rats
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RGD 和 YIGSR 通过肽自组装非共价键合到静电纺聚（ε-己内酯）导管上，协同促进大鼠坐骨神经再生
DOI：
10.1002/adhm.201600860
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发表时间：
2017
影响因子：
10
通讯作者：
Luo Zhuojing
中科院分区：
文献类型：
--
作者：
Zhu Lei;Wang Kai;Ma Teng;Huang Liangliang;Xia Bing;Zhu Shu;Yang Yafeng;Liu Zhongyang;Quan Xin;Luo Kai;Kong Deling;Huang Jinghui;Luo Zhuojing
具有生物功能的神经导管可以调节神经突起的生长，以及雪旺细胞的迁移、增殖和髓鞘形成活性。在本研究中，聚己内酯（PCL）导管通过自组装涂覆有萘-苯丙氨酸-苯丙氨酸-甘氨酸-精氨酸-甘氨酸-天冬氨酸（Nap-FFGRGD）和萘-苯丙氨酸-苯丙氨酸-甘氨酸-半胱氨酸-天冬氨酸-脯氨酸-甘氨酸-酪氨酸-异亮氨酸-甘氨酸-丝氨酸-精氨酸（Nap-FFGCDPGYIGSR）。体外研究表明，精氨酸-甘氨酸-天冬氨酸（RGD）和酪氨酸-异亮氨酸-甘氨酸-丝氨酸-精氨酸（YIGSR）能够协同增强PCL支持雪旺细胞粘附和增殖的能力，以及增加背根神经节外植体的神经突生长。这种协同效应可能通过激活磷酸肌醇3-激酶/蛋白激酶B和丝裂原活化蛋白激酶/细胞外信号调节蛋白激酶途径而发生。RGD/YIGSR修饰在轴突再生和功能恢复中跨越15 mm坐骨神经间隙表现出有益效果。此外，在RGD/YIGSR-PCL组中观察到血管化增加，这可能有助于其对神经再生的有益作用。这些发现表明了RGD/YIGSR-PCL导管促进轴突再生和功能恢复的潜力，使RGD/YIGSR-PCL导管成为治疗关键神经缺损的有吸引力的候选者。
The nerve conduit with biofunctionalities can regulate neurite outgrowth, as well as the migration, proliferation, and myelination activity of Schwann cells. In the present study, polycaprolactone (PCL) conduits are coated with Naphthalene‐phenylalanine‐phenylalanine‐glycine‐arginine‐glycine‐aspartic (Nap‐FFGRGD) and Naphthalene‐phenylalanine‐phenylalanine‐glycine‐cysteine‐aspartic‐proline‐glycine‐tyrosine‐isoleucine‐glycine‐serine‐arginine (Nap‐FFGCDPGYIGSR) by self‐assembly. In vitro studies demonstrate that arginine‐glycine‐aspartic (RGD) and tyrosine‐isoleucine‐glycine‐serine‐arginine (YIGSR) are capable of synergistically enhancing the ability of PCL to support the adhesion and proliferation of Schwann cells, as well as increasing neurite outgrowth from dorsal root ganglions explants. This synergistic effect may occur via the activation of both the phosphoinositide 3‐kinase/protein kinase B and mitogen‐activated protein kinase/extracellular signal‐regulated protein kinase pathways. RGD/YIGSR modifications demonstrate beneficial effects across a 15 mm sciatic nerve gap in axonal regeneration and functional recovery. In addition, increased vascularization is observed in the RGD/YIGSR‐PCL group, which might contribute to their beneficial effects on nerve regeneration. These findings indicate the potential of the RGD/YIGSR‐PCL conduit to promote axonal regeneration and functional recovery, making the RGD/YIGSR‐PCL conduit an attractive candidate for the treatment of a critical nerve defect.