Spatially Controlled Delivery of Neurotrophic Factors in Silk Fibroin-Based Nerve Conduits for Peripheral Nerve Repair
Spatially Controlled Delivery of Neurotrophic Factors in Silk Fibroin-Based Nerve Conduits for Peripheral Nerve Repair
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DOI：
10.1097/sap.0b013e3182240346
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发表时间：
2011-08-01
影响因子：
1.5
通讯作者：
Marra, Kacey G.
中科院分区：
文献类型：
--
作者：
Lin, Yen-Chih;Ramadan, Mostafa;Marra, Kacey G.
长间隙周围神经损伤后的功能恢复仍然是临床的挑战。由于其生物相容性，令人印象深刻的机械性能，以及食品和药物管理局的批准，丝绸在许多组织工程应用中显示出临床前景。本研究的目的是评价含有胶质细胞系来源的神经营养因子（GDNF）的丝素基神经导片在大鼠长间隙（15 mm）坐骨神经缺损模型中的效果。制备了四组神经导管：(1)空丝微球丝导管；(2)载GDNF的丝微球丝导管均匀分布于管壁；(3)载GDNF的丝微球丝导管，远端GDNF浓度最高；(4)等接。6周后，神经移植物被移植，收获，并固定用于组织学分析。用S-100和神经内分泌标记物PGP 9.5抗体染色的神经组织显示，与空微球（对照组）相比，gdnf处理组的神经组织密度显著增加（P < 0.05）。GDNF处理动物远端GDNF浓度较高，其导管中部PGP 9.5蛋白密度显著高于GDNF均匀处理动物（P < 0.05）。丝基神经导管具有良好的机械性能和降解性能，在周围神经修复中具有潜在的应用价值。该研究表明，以可控方式注入GDNF的新型多孔丝素神经导管代表了周围神经再生中雪旺细胞迁移和增殖的潜在可行管道。
Restoration with sufficient functional recovery after long-gap peripheral nerve damage remains a clinical challenge. Silk has shown clinical promise for numerous tissue engineering applications due to its biocompatibility, impressive mechanical properties, and Food and Drug Administration approval. The aim of this study was to evaluate the efficacy of silk fibroin-based nerve guides containing glial cell line-derived neurotrophic factor (GDNF) in a long-gap sized (15 mm) rat sciatic nerve defect model. Four groups of nerve conduits were prepared: (1) silk conduits with empty silk microspheres, (2) silk conduits with GDNF-loaded silk microspheres uniformly distributed in the conduit wall, (3) silk conduits with GDNF-loaded silk microspheres in a controlled manner with the highest GDNF concentration at the distal end, and (4) isograft. After 6 weeks, the nerve grafts were explanted, harvested, and fixed for histologic analysis. Nerve tissue stained with the S-100, and neuroendocrine marker PGP 9.5 antibodies demonstrated a significantly increased density of nerve tissue in the GDNF-treated groups compared with the empty microsphere (control) group (P < 0.05). GDNF-treated animals with a higher concentration of GDNF in the distal portion possessed a significantly higher density of PGP 9.5 protein middle conduit part than comparison to GDNF uniform-treated animals (P < 0.05). Silk-based nerve conduits possess optimal mechanical and degradative properties, rendering them potentially useful in peripheral nerve repair. This study demonstrates that novel, porous silk fibroin-based nerve conduits, infused with GDNF in a controlled manner, represent a potentially viable conduit for Schwann cell migration and proliferation in the regeneration of peripheral nerves.