工程性基于丝素蛋白的神经导管与神经营养因子对周围神经损伤后的近端保护,Advanced Healthcare Materials

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工程性基于丝素蛋白的神经导管与神经营养因子对周围神经损伤后的近端保护
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2020-11-09 , DOI: 10.1002/adhm.202000753
Cristiana R. Carvalho ₁ , Wei Chang ₂ , Joana Silva‐Correia ₁ , Rui L. Reis ₁ , Joaquim M. Oliveira ₁ , Joachim Kohn ₂

Affiliation

能够充分释放神经营养因子的人工神经导管被广泛研究以弥合神经缺陷。然而，神经损伤后近端区域缺乏神经营养因子及其在轴突逆行运输中的可见作用是导致神经再生不完全的因素之一。在此，制造了由丝素蛋白制成的高级导管，其可以结合生长因子并促进受伤后的有效再生。为此，开发了基于酶交联的丝素蛋白的导管，以用作控制传递神经营养因子的平台。使用两种不同的方法将神经生长因子和神经胶质细胞系衍生的神经营养因子（GDNF）结合在一起：i）交联和ii）吸收法。释放曲线通过ELISA技术测量。通过使用初级背根神经节在体外评估神经营养因子的生物活性。当植入大鼠10毫米的坐骨神经缺损中时，与自体移植物和普通丝素蛋白导管相比，GDNF加载的丝素蛋白导管显示出逆行性神经保护作用。因此，新颖的设计提出了逆行运输，神经元的保护和运动神经的神经支配的实质性改进。

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Engineering Silk Fibroin‐Based Nerve Conduit with Neurotrophic Factors for Proximal Protection after Peripheral Nerve Injury

Artificial nerve conduits capable of adequately releasing neurotrophic factors are extensively studied to bridge nerve defects. However, the lack of neurotrophic factors in the proximal area and their visible effects in axonal retrograde transport following nerve injury is one of the factors causing an incomplete nerve regeneration. Herein, an advanced conduit made of silk fibroin is produced, which can incorporate growth factors and promote an effective regeneration after injury. For that, enzymatically crosslinked silk fibroin‐based conduits are developed to be used as a platform for the controlled delivery of neurotrophic factors. Nerve growth factor and glial‐cell line derived neurotrophic factor (GDNF) are incorporated using two different methodologies: i) crosslinking and ii) absorption method. The release profile is measured by ELISA technique. The bioactivity of the neurotrophic factors is evaluated in vitro by using primary dorsal root ganglia. When implanted in a 10 mm sciatic nerve defect in rats, GDNF‐loaded silk fibroin conduits reveal retrograde neuroprotection as compared to autografts and plain silk fibroin conduit. Therefore, the novel design presents a substantial improvement of retrograde trafficking, neurons’ protection, and motor nerve reinnervation.

更新日期：2020-11-09

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