Department of Structural and Functional Biology Institute of Biology University of Campinas - UNICAMP Campinas Brazil.
Department of Materials Engineering Faculty of Mechanical Engineering University of Campinas - UNICAMP Campinas Brazil.
Brain Behav. 2017 Jun 30;7(8):e00755. doi: 10.1002/brb3.755. eCollection 2017 Aug.
Injuries to peripheral nerves generate disconnection between spinal neurons and the target organ. Due to retraction of the nerve stumps, end-to-end neurorrhaphy is usually unfeasible. In such cases, autologous grafts are widely used, nonetheless with some disadvantages, such as mismatching of donor nerve dimensions and formation of painful neuromas at the donor area. Tubulization, using bioresorbable polymers, can potentially replace nerve grafting, although improvements are still necessary. Among promising bioresorbable synthetic polymers, poly(l-lactic acid) (PLLA) and poly(ε-caprolactone) (PCL) are the most studied. Carbon nanotubes and graphene sheets have been proposed, however, as adjuvants to improve mechanical and regenerative properties of tubular prostheses. Thus, the present work evaluated nerve tubulization repair following association of PCL with nanoparticles of carbon (NPC) and graphene (NPG).
For that, adult Lewis rats were subjected to unilateral sciatic nerve tubulization and allowed to survive for up to 8 and 12 weeks postsurgery.
Nanocomposites mechanical/chemical evaluation showed that nanoparticles do not alter PCL crystallinity, yet providing reinforcement of polymer matrix. Thus, there was a decrease in the enthalpy of melting when the mixture of PCL + NPC + NPG was used. Nanocomposites displayed positive changes in molecular mobility in the amorphous phase of the polymer. Also, the loss modulus (E") and the glass transition exhibited highest values for PCL + NPC + NPG. Scanning electron microscopy analysis revealed that PCL + NPC + NPG prostheses showed improved cell adhesion as compared to PCL alone. Surgical procedures with PCL + NPC + NPG were facilitated due to improved flexibility of the prosthesis, resulting in better stump positioning accuracy. In turn, a twofold increased number of myelinated axons was found in such repaired nerves. Consistent with that, target muscle atrophy protection has been observed.
Overall, the present data show that nanocomposite PCL tubes facilitate nerve repair and result in a better regenerative outcome, what may, in turn, represent a new alternative to pure PCL or PLLA prostheses.
周围神经损伤会导致脊髓神经元与靶器官之间的连接中断。由于神经残端回缩，端端神经吻合术通常不可行。在这种情况下，自体移植物被广泛应用，但存在一些缺点，如供体神经尺寸不匹配和供体部位形成疼痛性神经瘤。使用生物可吸收聚合物的套管化可能会替代神经移植，但仍需要改进。在有前途的生物可吸收合成聚合物中，聚（L-乳酸）（PLLA）和聚（ε-己内酯）（PCL）是研究最多的。然而，碳纳米管和石墨烯片已被提议作为佐剂，以改善管状假体的机械和再生性能。因此，本研究评估了 PCL 与纳米颗粒碳（NPC）和石墨烯（NPG）结合后的神经套管修复。
为此，成年 Lewis 大鼠接受单侧坐骨神经套管化，并允许在手术后 8 至 12 周内存活。
纳米复合材料的机械/化学评估表明，纳米颗粒不会改变 PCL 的结晶度，但能增强聚合物基质。因此，当使用 PCL+NPC+NPG 混合物时，熔融焓降低。纳米复合材料在聚合物非晶相的分子迁移方面显示出积极的变化。此外，损耗模量（E"）和玻璃化转变温度也表现出 PCL+NPC+NPG 的最高值。扫描电子显微镜分析显示，与单独使用 PCL 相比，PCL+NPC+NPG 假体具有更好的细胞粘附性。由于假体的柔韧性提高，PCL+NPC+NPG 的手术操作更加方便，从而提高了残端定位的准确性。反过来，在这种修复的神经中发现有髓神经轴的数量增加了两倍。与之一致的是，观察到靶肌肉萎缩的保护。
总的来说，本研究数据表明，纳米复合 PCL 管促进神经修复，并产生更好的再生结果，这反过来可能成为纯 PCL 或 PLLA 假体的新替代方案。
