Manoukian Ohan S, Rudraiah Swetha, Arul Michael R, Bartley Jenna M, Baker Jiana T, Yu Xiaojun, Kumbar Sangamesh G
Department of Biomedical Engineering, University of Connecticut, Storrs, CT, USA.
Department of Orthopedic Surgery, University of Connecticut Health, Farmington, CT, USA.
Bioact Mater. 2021 Feb 22;6(9):2881-2893. doi: 10.1016/j.bioactmat.2021.02.016. eCollection 2021 Sep.
Peripheral nerve injuries account for roughly 3% of all trauma patients with over 900,000 repair procedures annually in the US. Of all extremity peripheral nerve injuries, 51% require nerve repair with a transected gap. The current gold-standard treatment for peripheral nerve injuries, autograft repair, has several shortcomings. Engineered constructs are currently only suitable for short gaps or small diameter nerves. Here, we investigate novel nerve guidance conduits with aligned microchannel porosity that deliver sustained-release of neurogenic 4-aminopyridine (4-AP) for peripheral nerve regeneration in a critical-size (15 mm) rat sciatic nerve transection model. The results of functional walking track analysis, morphometric evaluations of myelin development, and histological assessments of various markers confirmed the equivalency of our drug-conduit with autograft controls. Repaired nerves showed formation of thick myelin, presence of S100 and neurofilament markers, and promising functional recovery. The conduit's aligned microchannel architecture may play a vital role in physically guiding axons for distal target reinnervation, while the sustained release of 4-AP may increase nerve conduction, and in turn synaptic neurotransmitter release and upregulation of critical Schwann cell neurotrophic factors. Overall, our nerve construct design facilitates efficient and efficacious peripheral nerve regeneration via a drug delivery system that is feasible for clinical applications.
在美国，周围神经损伤约占所有创伤患者的3%，每年有超过90万例修复手术。在所有肢体周围神经损伤中，51%需要对横断间隙进行神经修复。目前治疗周围神经损伤的金标准——自体移植修复，存在几个缺点。工程构建物目前仅适用于短间隙或小直径神经。在此，我们研究了具有排列微通道孔隙率的新型神经引导导管，其能在临界尺寸（15毫米）大鼠坐骨神经横断模型中实现神经源性4-氨基吡啶（4-AP）的持续释放，以促进周围神经再生。功能行走轨迹分析、髓鞘发育的形态计量学评估以及各种标志物的组织学评估结果证实了我们的药物导管与自体移植对照等效。修复后的神经显示出厚髓鞘的形成、S100和神经丝标志物的存在以及良好的功能恢复。导管排列的微通道结构可能在物理引导轴突进行远端靶标再支配方面发挥至关重要的作用，而4-AP的持续释放可能增加神经传导，进而增加突触神经递质释放以及关键雪旺细胞神经营养因子的上调。总体而言，我们的神经构建物设计通过一种对临床应用可行的药物递送系统促进了高效且有效的周围神经再生。
