A bioengineered peripheral nerve construct using aligned peptide amphiphile nanofibers.
A bioengineered peripheral nerve construct using aligned peptide amphiphile nanofibers.
复制标题
DOI：
10.1016/j.biomaterials.2014.06.049
复制
发表时间：
2014-10
期刊：
影响因子：
14
通讯作者：
Jarrahy, Reza
中科院分区：
文献类型：
--
作者：
Li, Andrew;Hokugo, Akishige;Yalom, Anisa;Berns, Eric J.;Stephanopoulos, Nicholas;McClendon, Mark T.;Segovia, Luis A.;Spigelman, Igor;Stupp, Samuel I.;Jarrahy, Reza
周围神经损伤可导致终身残疾。当横断神经末端之间的间隙较短时，初次接合是首选治疗方法。在更复杂的损伤中出现的长神经间隙通常需要自体神经移植或神经导管进行修复。然而，神经移植会导致供体部位发病和功能丧失，而供体部位的数量有限。反过来，神经导管缺乏支持和引导轴突再生的内部支架，导致神经间隙长度较长时功效降低。相比之下，肽两亲物（PA）是可以自组装成纳米纤维的分子，纳米纤维可以排列成模仿周围神经的天然结构。因此，它们代表了用于生物工程神经移植替代品的潜在基质。为了检查这一点，我们用生物活性 PA（RGDS-PA、IKVAV-PA）培养雪旺细胞，以确定它们附着在生物材料上并在生物材料内增殖的能力。接下来，我们设计了一种用于周围神经临界尺寸缺陷模型的 PA 结构。大鼠坐骨神经缺损是用自体神经、填充有各种形式的对齐 PA 的 PLGA 导管创建和重建的，或者不修复。确定并比较各组之间的运动和感觉恢复情况。我们的结果表明，雪旺细胞能够在对齐的 PA 凝胶上粘附并增殖，与单独的主链 PA 相比，在生物活性 PA 中具有更高的功效。体内测试表明，用导管/PA 结构治疗的动物运动和感觉功能的恢复与用自体神经移植物治疗的动物相当。导管/PA 和自体移植组的功能恢复明显快于用空 PLGA 导管治疗的动物。组织学检查还表明，在用导管/PA 构建体治疗的动物中，重建神经间隙内的轴突和雪旺细胞再生增加。这些结果表明 PA 纳米纤维可能是一种有前途的生物材料，可用于生物工程周围神经修复。
Peripheral nerve injuries can result in lifelong disability. Primary coaptation is the treatment of choice when the gap between transected nerve ends is short. Long nerve gaps seen in more complex injuries often require autologous nerve grafts or nerve conduits implemented into the repair. Nerve grafts, however, cause morbidity and functional loss at donor sites, which are limited in number. Nerve conduits, in turn, lack an internal scaffold to support and guide axonal regeneration, resulting in decreased efficacy over longer nerve gap lengths. By comparison, peptide amphiphiles (PAs) are molecules that can self-assemble into nanofibers, which can be aligned to mimic the native architecture of peripheral nerve. As such, they represent a potential substrate for use in a bioengineered nerve graft substitute. To examine this, we cultured Schwann cells with bioactive PAs (RGDS-PA, IKVAV-PA) to determine their ability to attach to and proliferate within the biomaterial. Next, we devised a PA construct for use in a peripheral nerve critical sized defect model. Rat sciatic nerve defects were created and reconstructed with autologous nerve, PLGA conduits filled with various forms of aligned PAs, or left unrepaired. Motor and sensory recovery were determined and compared among groups. Our results demonstrate that Schwann cells are able to adhere to and proliferate in aligned PA gels, with greater efficacy in bioactive PAs compared to the backbone-PA alone. In vivo testing revealed recovery of motor and sensory function in animals treated with conduit/PA constructs comparable to animals treated with autologous nerve grafts. Functional recovery in conduit/PA and autologous graft groups was significantly faster than in animals treated with empty PLGA conduits. Histological examinations also demonstrated increased axonal and Schwann cell regeneration within the reconstructed nerve gap in animals treated with conduit/PA constructs. These results indicate that PA nanofibers may represent a promising biomaterial for use in bioengineered peripheral nerve repair.
登录
查看更多内容
影响因子：
1.9
作者：
Bushnell, Brandon D.;McWilliams, Andrew D.;Messer, Terry M.
通讯作者：
Messer, Terry M.
影响因子：
--
作者：
Armstrong, Stephanie J.;Wiberg, Mikael;Kingham, Paul J.
通讯作者：
Kingham, Paul J.
影响因子：
3.3
作者：
Matsuka, Yoshizo;Ono, Takeshi;Spigelman, Igor
通讯作者：
Spigelman, Igor
影响因子：
4.9
作者：
Gunn, JW;Turner, SD;Mann, BK
通讯作者：
Mann, BK
影响因子：
3.4
作者：
Castañeda, F;Kinne, RKH
通讯作者：
Kinne, RKH