The Efficacy of a Scaffold-free Bio 3D Conduit Developed from Autologous Dermal Fibroblasts on Peripheral Nerve Regeneration in a Canine Ulnar Nerve Injury Model: A Preclinical Proof-of-Concept Study
The Efficacy of a Scaffold-free Bio 3D Conduit Developed from Autologous Dermal Fibroblasts on Peripheral Nerve Regeneration in a Canine Ulnar Nerve Injury Model: A Preclinical Proof-of-Concept Study
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DOI：
10.1177/0963689719855346
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发表时间：
2019-09-01
影响因子：
3.3
通讯作者：
Matsuda, Shuichi
中科院分区：
文献类型：
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作者：
Mitsuzawa, Sadaki;Ikeguchi, Ryosuke;Matsuda, Shuichi
自体神经移植被广泛认为是治疗节段性神经缺损的金标准。为了克服原始方法不可避免的缺点，已经开发了替代方法，例如管状技术。几项研究调查了理想神经导管在支持细胞、支架、生长因子和血管分布方面的特征。此前，我们证实由人真皮成纤维细胞制造的生物无支架导管可促进大鼠坐骨神经损伤模型中的神经再生。本研究的目的是利用大型动物模型评估由自体真皮成纤维细胞组成的生物无支架导管的可行性。本研究使用了六只雄性比格犬。手术前八周，从腹股沟皮肤采集真皮成纤维细胞并在培养物中生长。 Bio 3D 导管是使用 Bio 3D 打印机从增殖的真皮成纤维细胞组装而成的。在全身麻醉下暴露每只狗前肢的尺神经，并锐利切割以形成 5 毫米的断端间隙，由准备好的 8 毫米 Bio 3D 导管桥接。手术后十周，研究了神经再生。电生理学研究检测了所有动物小鱼际肌肉的复合肌肉动作电位（CMAP）和运动神经传导速度（MNCV）。肉眼观察显示尺神经再生。证实有低度小鱼际肌萎缩。免疫组织化学、组织学和形态测量研究证实，通过 Bio 3D 导管存在许多有髓鞘轴突。没有报告严重不良事件。小鱼际肌肉通过 Bio 3D 导管由再生神经纤维重新支配。由自体真皮成纤维细胞制成的无支架 Bio 3D 导管可有效促进犬尺神经损伤模型的神经再生。该技术在临床前环境中作为周围神经损伤和节段神经缺陷的治疗是可行的。
Autologous nerve grafting is widely accepted as the gold standard treatment for segmental nerve defects. To overcome the inevitable disadvantages of the original method, alternative methods such as the tubulization technique have been developed. Several studies have investigated the characteristics of an ideal nerve conduit in terms of supportive cells, scaffolds, growth factors, and vascularity. Previously, we confirmed that biological scaffold-free conduits fabricated from human dermal fibroblasts promote nerve regeneration in a rat sciatic nerve injury model. The purpose of this study is to evaluate the feasibility of biological scaffold-free conduits composed of autologous dermal fibroblasts using a large-animal model. Six male beagle dogs were used in this study. Eight weeks before surgery, dermal fibroblasts were harvested from their groin skin and grown in culture. Bio 3D conduits were assembled from proliferating dermal fibroblasts using a Bio 3D printer. The ulnar nerve in each dog's forelimb was exposed under general anesthesia and sharply cut to create a 5 mm interstump gap, which was bridged by the prepared 8 mm Bio 3D conduit. Ten weeks after surgery, nerve regeneration was investigated. Electrophysiological studies detected compound muscle action potentials (CMAPs) of the hypothenar muscles and motor nerve conduction velocity (MNCV) in all animals. Macroscopic observation showed regenerated ulnar nerves. Low-level hypothenar muscle atrophy was confirmed. Immunohistochemical, histological, and morphometric studies confirmed the existence of many myelinated axons through the Bio 3D conduit. No severe adverse event was reported. Hypothenar muscles were re-innervated by regenerated nerve fibers through the Bio 3D conduit. The scaffold-free Bio 3D conduit fabricated from autologous dermal fibroblasts is effective for nerve regeneration in a canine ulnar nerve injury model. This technology was feasible as a treatment for peripheral nerve injury and segmental nerve defects in a preclinical setting.