Severe injuries to peripheral nerves are challenging to repair. Standard-of-care treatment for nerve gaps >2 to 3 centimeters is autografting; however, autografting can result in neuroma formation, loss of sensory function at the donor site, and increased operative time. To address the need for a synthetic nerve conduit to treat large nerve gaps, we investigated a biodegradable poly(caprolactone) (PCL) conduit with embedded double-walled polymeric microspheres encapsulating glial cell line-derived neurotrophic factor (GDNF) capable of providing a sustained release of GDNF for >50 days in a 5-centimeter nerve defect in a rhesus macaque model. The GDNF-eluting conduit (PCL/GDNF) was compared to a median nerve autograft and a PCL conduit containing empty microspheres (PCL/Empty). Functional testing demonstrated similar functional recovery between the PCL/GDNF-treated group (75.64 ± 10.28%) and the autograft-treated group (77.49 ± 19.28%); both groups were statistically improved compared to PCL/Empty-treated group (44.95 ± 26.94%). Nerve conduction velocity 1 year after surgery was increased in the PCL/GDNF-treated macaques (31.41 ± 15.34 meters/second) compared to autograft (25.45 ± 3.96 meters/second) and PCL/Empty (12.60 ± 3.89 meters/second) treatment. Histological analyses included assessment of Schwann cell presence, myelination of axons, nerve fiber density, and g-ratio. PCL/GDNF group exhibited a statistically greater average area occupied by individual Schwann cells at the distal nerve (11.60 ± 33.01 μm2) compared to autograft (4.62 ± 3.99 μm2) and PCL/Empty (4.52 ± 5.16 μm2) treatment groups. This study demonstrates the efficacious bridging of a long peripheral nerve gap in a nonhuman primate model using an acellular, biodegradable nerve conduit.

中文翻译：

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通过持续释放非人类灵长类动物中的神经营养因子来修复周围神经。

周围神经严重受伤很难修复。自体移植是治疗神经间隙大于2至3厘米的标准护理。然而，自体移植可导致神经瘤形成，供体部位感觉功能丧失和手术时间增加。为了满足对合成神经导管治疗大神经间隙的需求，我们研究了一种可生物降解的聚己内酯（PCL）导管，该导管具有嵌入的双壁聚合物微球，该双微球包裹胶质细胞系衍生的神经营养因子（GDNF），能够提供持续的在恒河猴模型的5厘米神经缺损中，GDNF释放> 50天。将GDNF洗脱导管（PCL / GDNF）与中位神经自体移植和包含空微球的PCL导管（PCL / Empty）进行了比较。功能测试表明，PCL / GDNF治疗组（75.64±10.28％）和自体移植治疗组（77.49±19.28％）的功能恢复相似；与PCL / Empty治疗组相比，两组均在统计学上有所改善（44.95±26.94％）。与自体移植（25.45±3.96米/秒）和PCL /空（12.60±3.89米/秒）处理相比，PCL / GDNF处理的猕猴（31.41±15.34米/秒）术后1年神经传导速度增加。组织学分析包括评估雪旺氏细胞的存在，轴突的髓鞘形成，神经纤维密度和g-比率。与自体移植（4.62±3.99μm2）和PCL / Empty（4.52±5.16μm2）治疗组相比，PCL / GDNF组在远端神经处的单个Schwann细胞占据的统计学平均面积更大（11.60±33.01μm2）。