Promising biomaterials should be tested in appropriate large animal models that recapitulate human inflammatory and regenerative responses. Previous studies have shown tyrosine‐derived polycarbonates (TyrPC) are versatile biomaterials with a wide range of applications across multiple disciplines. The library of TyrPC has been well studied and consists of thousands of polymer compositions with tunable mechanical characteristics and degradation and resorption rates that are useful for nerve guidance tubes (NGTs). NGTs made of different TyrPCs have been used in segmental nerve defect models in small animals. The current study is an extension of this work and evaluates NGTs made using two different TyrPC compositions in a 1 cm porcine peripheral nerve repair model. We first evaluated a nondegradable TyrPC formulation, demonstrating proof‐of‐concept chronic regenerative efficacy up to 6 months with similar nerve/muscle electrophysiology and morphometry to the autograft repair control. Next, we characterized the acute regenerative response using a degradable TyrPC formulation. After 2 weeks in vivo, TyrPC NGT promoted greater deposition of pro‐regenerative extracellular matrix (ECM) constituents (in particular collagen I, collagen III, collagen IV, laminin, and fibronectin) compared to commercially available collagen‐based NGTs. This corresponded with dense Schwann cell infiltration and axon extension across the lumen. These findings confirmed results reported previously in a mouse model and reveal that TyrPC NGTs were well tolerated in swine and facilitated host axon regeneration and Schwann cell infiltration in the acute phase across segmental defects ‐ likely by eliciting a favorable neurotrophic ECM milieu. This regenerative response ultimately can contribute to functional recovery.

中文翻译：

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当用于桥接猪的节段性神经缺陷时，酪氨酸衍生的聚碳酸酯神经引导管会引起再生细胞外基质沉积

有前途的生物材料应在适当的大型动物模型中进行测试，以概括人类炎症和再生反应。先前的研究表明，酪氨酸衍生的聚碳酸酯 (TyrPC) 是一种多功能生物材料，在多个学科中具有广泛的应用。TyrPC 库已经过充分研究，由数千种具有可调机械特性和降解和再吸收率的聚合物组合物组成，可用于神经引导管 (NGT)。由不同 TyrPC 制成的 NGT 已用于小动物的节段性神经缺损模型。目前的研究是这项工作的延伸，并评估在 1 cm 猪周围神经修复模型中使用两种不同 TyrPC 组合物制成的 NGT。我们首先评估了一种不可降解的 TyrPC 配方，证明了长达 6 个月的概念验证慢性再生功效，具有与自体移植修复对照相似的神经/肌肉电生理学和形态测量学。接下来，我们使用可降解的 TyrPC 制剂表征了急性再生反应。在体内 2 周后，与市售的基于胶原蛋白的 NGT 相比，TyrPC NGT 促进了更多的促再生细胞外基质 (ECM) 成分（特别是胶原蛋白 I、胶原蛋白 III、胶原蛋白 IV、层粘连蛋白和纤连蛋白）的沉积。这对应于密集的雪旺细胞浸润和跨腔的轴突延伸。这些发现证实了之前在小鼠模型中报告的结果，并揭示了 TyrPC NGT 在猪中具有良好的耐受性，并在急性期通过节段性缺损促进宿主轴突再生和施万细胞浸润——可能是通过引发有利的神经营养 ECM 环境。这种再生反应最终有助于功能恢复。