中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (7): 1247-1252.doi: 10.4103/1673-5374.235063

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

可控制释放他克莫司的微图案化聚乳酸乙醇酸膜：在外周神经修复中的应用潜力

  

  • 收稿日期:2018-05-06 出版日期:2018-07-15 发布日期:2018-07-15

Controlled release of FK506 from micropatterned PLGA films: potential for application in peripheral nerve repair

Brett Davis1, 2, Susan Wojtalewicz1, Pratima Labroo2, 3, Jill Shea2, Himanshu Sant3, Bruce Gale3, Jayant Agarwal2   

  1. 1 Department of Bioengineering, University of Utah, Salt Lake City, UT, USA;
    2 Department of Surgery, University of Utah, Salt Lake City, UT, USA;
    3 Department of Mechanical Engineering, University of Utah, Salt Lake City, UT, USA
  • Received:2018-05-06 Online:2018-07-15 Published:2018-07-15
  • Contact: Jayant Agarwal, M.D.,jay.agarwal@hsc.utah.edu

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摘要：

目前临床上可用的神经导管仅可引导再生轴突穿过神经缺损，并不能改善神经细胞功能。FK506（他克莫司）作为一种免疫抑制剂，已被证明能够增强周围神经的再生，但是在系统性输送时会带来严重的副作用。此次研究的目的在于开发和评估局部控制释放FK506的生物可吸收药物传递系统在引导轴突生长方面的拓扑引导特性。实验使用光刻法制造嵌有FK506的微图案化聚乳酸乙醇酸（PLGA）膜。制造并表征了未加图案的10/10 μm（脊/凹槽宽度）和负载有0, 1和3 μg/cm2 FK506的30/30μm图案薄膜。体外FK506释放速率测试表明，该膜能够延长（至少56d）、控制和定量FK506的释放。神经突延伸生物活性测定结果显示，从膜中释放的FK506可保持其神经生物活性，并促进神经突延伸。此次研究开发的多功能FK506嵌入式微图案化PLGA薄膜在用于周围神经修复方面具有潜力。

orcid:0000-0002-1209-6703(Jayant Agarwal)

关键词: FK506, 控制释放, 微图案, 拓扑线索, PLGA, 组织工程, 神经再生

Abstract:

After decades of research, peripheral nerve injury and repair still frequently results in paralysis, chronic pain and neuropathies leading to severe disability in patients. Current clinically available nerve conduits only provide crude guidance of regenerating axons across nerve gap without additional functionality.FK506 (Tacrolimus), an FDA approved immunosuppressant, has been shown to enhance peripheral nerve regeneration but carries harsh side-effects when delivered systemically. The objective of this study was to develop and evaluate a bioresorbable drug delivery system capable of local extended delivery of FK506 that also provides topological guidance cues to guide axon growth via microgrooves. Photolithography was used to create micropatterned poly(lactide-co-glycolic acid) (PLGA) films embedded with FK506. Non-patterned,10/10 μm (ridge/groove width), and 30/30 μm patterned films loaded with 0, 1, and 3 μg/cm2 FK506 were manufactured and characterized. In vitro FK506 rate of release testing indicated that the films are capable of an extended (at least 56 days), controlled, and scalable release of FK506. Neurite extension bioactivity assay indicated that FK506 released from the films (concentration of samples tested ranged between 8.46–19.7 ng/mL) maintained its neural bioactivity and promoted neurite extension similar to control FK506 dosages (10 ng/mL FK506). The multi-functional FK506 embedded, micropatterned poly(lactide-co-glycolic acid) films developed in this study have potential to be used in the construction of peripheral nerve repair devices.

Key words: nerve regeneration, FK506, controlled release, micropatterns, topological cues, PLGA