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Preclinical study of peripheral nerve regeneration using nerve guidance conduits based on polyhydroxyalkanaotes
Bioengineering & Translational Medicine ( IF 6.1 ) Pub Date : 2021-05-04 , DOI: 10.1002/btm2.10223 Lorena R Lizarraga-Valderrama 1, 2 , Giulia Ronchi 3, 4 , Rinat Nigmatullin 1, 5 , Federica Fregnan 3, 4 , Pooja Basnett 1 , Alexandra Paxinou 1 , Stefano Geuna 3, 4 , Ipsita Roy 6
Bioengineering & Translational Medicine ( IF 6.1 ) Pub Date : 2021-05-04 , DOI: 10.1002/btm2.10223 Lorena R Lizarraga-Valderrama 1, 2 , Giulia Ronchi 3, 4 , Rinat Nigmatullin 1, 5 , Federica Fregnan 3, 4 , Pooja Basnett 1 , Alexandra Paxinou 1 , Stefano Geuna 3, 4 , Ipsita Roy 6
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Nerve guidance conduits (NGCs) are used as an alternative to the “gold standard” nerve autografting, preventing the need for surgical intervention required to harvest autologous nerves. However, the regeneration outcomes achieved with the current NGCs are only comparable with autografting when the gap is short (less than 10 mm). In the present study, we have developed NGCs made from a blend of polyhydroxyalkanoates, a family of natural resorbable polymers. Hollow NGCs made from a 75:25 poly(3-hydroxyoctanoate)/poly(3-hydroxybutyrate) blend (PHA-NGCs) were manufactured using dip-molding. These PHA-NGCs showed appropriate flexibility for peripheral nerve regeneration. In vitro cell studies performed using RT4-D6P2T rat Schwann cell line confirmed that the material is capable of sustaining cell proliferation and adhesion. PHA-NGCs were then implanted in vivo to repair 10 mm gaps of the median nerve of female Wistar rats for 12 weeks. Functional evaluation of the regenerated nerve using the grasping test showed that PHA-NGCs displayed similar motor recovery as the autograft, starting from week 7. Additionally, nerve cross-sectional area, density and number of myelinated cells, as well as axon diameter, fiber diameter, myelin thickness and g-ratio obtained using the PHA-NGCs were found comparable to an autograft. This preclinical data confirmed that the PHA-NGCs are indeed highly promising candidates for peripheral nerve regeneration.
中文翻译：
基于聚羟基脂肪酸酯的神经导管再生周围神经的临床前研究
神经引导导管（NGC）被用作“金标准”自体神经移植的替代品，从而无需进行手术干预来获取自体神经。然而，当前 NGC 实现的再生效果仅在间隙较短（小于 10 毫米）时才能与自体移植相媲美。在本研究中，我们开发了由聚羟基脂肪酸酯（一种天然可吸收聚合物）混合物制成的 NGC。采用浸塑法制造由 75:25 聚（3-羟基辛酸酯）/聚（3-羟基丁酸酯）共混物（PHA-NGC）制成的中空 NGC。这些 PHA-NGC 对周围神经再生表现出适当的灵活性。使用 RT4-D6P2T 大鼠雪旺细胞系进行的体外细胞研究证实，该材料能够维持细胞增殖和粘附。然后将 PHA-NGC 植入体内，修复雌性 Wistar 大鼠正中神经 10 毫米的间隙，持续 12 周。使用抓握测试对再生神经进行功能评估表明，从第 7 周开始，PHA-NGC 表现出与自体移植物相似的运动恢复。此外，神经横截面积、有髓鞘细胞密度和数量，以及轴突直径、纤维使用 PHA-NGC 获得的直径、髓磷脂厚度和 g 比与自体移植物相当。该临床前数据证实，PHA-NGC 确实是周围神经再生非常有前途的候选者。
更新日期：2021-05-04
中文翻译：
基于聚羟基脂肪酸酯的神经导管再生周围神经的临床前研究
神经引导导管（NGC）被用作“金标准”自体神经移植的替代品，从而无需进行手术干预来获取自体神经。然而，当前 NGC 实现的再生效果仅在间隙较短（小于 10 毫米）时才能与自体移植相媲美。在本研究中，我们开发了由聚羟基脂肪酸酯（一种天然可吸收聚合物）混合物制成的 NGC。采用浸塑法制造由 75:25 聚（3-羟基辛酸酯）/聚（3-羟基丁酸酯）共混物（PHA-NGC）制成的中空 NGC。这些 PHA-NGC 对周围神经再生表现出适当的灵活性。使用 RT4-D6P2T 大鼠雪旺细胞系进行的体外细胞研究证实，该材料能够维持细胞增殖和粘附。然后将 PHA-NGC 植入体内，修复雌性 Wistar 大鼠正中神经 10 毫米的间隙，持续 12 周。使用抓握测试对再生神经进行功能评估表明，从第 7 周开始，PHA-NGC 表现出与自体移植物相似的运动恢复。此外，神经横截面积、有髓鞘细胞密度和数量，以及轴突直径、纤维使用 PHA-NGC 获得的直径、髓磷脂厚度和 g 比与自体移植物相当。该临床前数据证实，PHA-NGC 确实是周围神经再生非常有前途的候选者。
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