Zhukauskas Rasa, Fischer Debbie Neubauer, Deister Curt, Faleris Jennifer, Marquez-Vilendrer Stefanie B, Mercer Deana
Axogen Corporation, Alachua, FL.
University of New Mexico, Albuquerque, NM.
J Hand Surg Glob Online. 2023 Aug 30;5(6):810-817. doi: 10.1016/j.jhsg.2023.07.014. eCollection 2023 Nov.
After nerve injury, macrophages and Schwann cells remove axon and myelin debris. We hypothesized that nerves repaired with different conduit materials will result in varying levels of these cell populations, which impacts Wallerian degeneration and axonal regeneration.
We performed a unilateral sciatic nerve transection in 18 rats. The nerves were repaired with small intestine submucosa (SIS, n = 9) or isolated type-I collagen (CLC, n = 9) conduits. Rats were monitored for 4 weeks. Histology samples were obtained from the proximal nerve, mid-implant, and distal nerve regions. Samples were stained for total macrophages, M2 macrophages, foamy phagocytes, Schwann cells, vascular components, axon components, and collagen density.
Distal nerve analyses showed higher populations of total macrophages and M2 macrophages in SIS-repaired nerves and higher density of foamy phagocytes in CLC-repaired nerves. Proximal nerve, mid-implant, and distal nerve analyses showed higher Schwann cell and vascular component densities in SIS-repaired nerves. Axon density was higher in the mid-implant region of SIS-repaired nerves. Collagen staining in the mid-implant was scant, but less collagen density was observed in SIS-repaired versus CLC-repaired nerves.
In the distal nerve, the following were observed: (1) lower total macrophages in CLC-repaired nerves, suggesting lower overall inflammation versus SIS-repaired nerves; (2) higher M2 macrophages in SIS-repaired versus CLC-repaired nerves, a driving factor for higher total macrophages and indicative of an inflammation resolution response in SIS-repaired nerves; and (3) a lower foamy phagocyte density in SIS-repaired nerves, suggesting earlier resolution of Wallerian degeneration versus CLC-repaired nerves. In the proximal nerve, mid-implant, and distal nerve, higher Schwann cell and vascular component densities were noted in SIS-repaired nerves. In the mid-implant, a higher axon component density and a lower collagen density of the SIS-repaired nerves versus CLC-repaired nerves were noted. These results indicate more robust nerve regeneration with less collagen deposition.
This in vivo study evaluated two common conduit materials that are used in peripheral nerve repair. Clinical outcomes of nerves repaired with conduits may be impacted by the response to different conduit materials. These nerve repair responses include Wallerian degeneration, nerve regeneration, and nerve scarring. This study evaluated Wallerian degeneration using total macrophages, M2 macrophages, and foamy phagocytes. Nerve regeneration was evaluated using Schwann cells and axons. Nerve scarring was evaluated using vascular and collagen density.
神经损伤后，巨噬细胞和施万细胞会清除轴突和髓磷脂碎片。我们推测，使用不同导管材料修复神经会导致这些细胞群的水平不同，进而影响沃勒变性和轴突再生。
我们对18只大鼠进行了单侧坐骨神经横断术。使用小肠黏膜下层（SIS，n = 9）或分离的I型胶原（CLC，n = 9）导管修复神经。对大鼠进行4周的监测。从近端神经、植入物中部和远端神经区域获取组织学样本。样本进行总巨噬细胞、M2巨噬细胞、泡沫吞噬细胞、施万细胞、血管成分、轴突成分和胶原密度染色。
远端神经分析显示，SIS修复的神经中总巨噬细胞和M2巨噬细胞数量较多，而CLC修复的神经中泡沫吞噬细胞密度较高。近端神经、植入物中部和远端神经分析显示，SIS修复的神经中施万细胞和血管成分密度较高。SIS修复的神经植入物中部区域的轴突密度较高。植入物中部的胶原染色较少，但与CLC修复的神经相比，SIS修复的神经中胶原密度较低。
在远端神经中，观察到以下情况：（1）CLC修复的神经中总巨噬细胞较少，表明与SIS修复的神经相比，整体炎症较低；（2）SIS修复的神经中M2巨噬细胞高于CLC修复的神经，这是总巨噬细胞较高的驱动因素，表明SIS修复的神经中有炎症消退反应；（3）SIS修复的神经中泡沫吞噬细胞密度较低，表明与CLC修复的神经相比，沃勒变性的消退更早。在近端神经、植入物中部和远端神经中，SIS修复的神经中施万细胞和血管成分密度较高。在植入物中部，与CLC修复的神经相比，SIS修复的神经中轴突成分密度较高，胶原密度较低。这些结果表明神经再生更强，胶原沉积更少。
这项体内研究评估了两种用于周围神经修复的常见导管材料。使用导管修复神经的临床结果可能会受到对不同导管材料反应的影响。这些神经修复反应包括沃勒变性、神经再生和神经瘢痕形成。本研究使用总巨噬细胞、M2巨噬细胞和泡沫吞噬细胞评估沃勒变性。使用施万细胞和轴突评估神经再生。使用血管和胶原密度评估神经瘢痕形成。
