Engineered neuronal microtissue provides exogenous axons for delayed nerve fusion and rapid neuromuscular recovery in rats.
Engineered neuronal microtissue provides exogenous axons for delayed nerve fusion and rapid neuromuscular recovery in rats.
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DOI：
10.1016/j.bioactmat.2022.03.018
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发表时间：
2022-12
影响因子：
18.9
通讯作者：
Cullen DK
中科院分区：
文献类型：
--
作者：
Burrell JC;Das S;Laimo FA;Katiyar KS;Browne KD;Shultz RB;Tien VJ;Vu PT;Petrov D;Ali ZS;Rosen JM;Cullen DK
需要手术修复的神经损伤通常会导致功能恢复不佳，因为宿主轴突无法长出很长的距离，也无法重建与靶肌肉的有意义的连接。虽然外科医生可以将局部轴突束重新路由到目标肌肉，但没有技术可以在不牺牲健康神经的情况下提供外源性轴突来源。因此，我们开发了组织工程神经肌肉接口(TE-NMI)，作为第一个以解剖学为灵感的架构中包含运动神经元和感觉神经元的可注射微组织。TE-NMI提供轴突束，旨在与失神经的远端结构整合，并在没有宿主神经支配的情况下在较长的时间内保持再生能力。植入后，我们发现TE-NMI轴突促进了雪旺细胞的维持，与远端肌肉整合，并在没有宿主轴突神经支配的情况下，在神经切断后20周保存了诱发的肌肉反应。通过用外源性轴突重新填充远端鞘，TE-NMI还使推测的与近端宿主轴突的延迟融合成为可能，这一现象以前在由于远端轴突变性而延迟修复的情况下无法实现。在这里，我们发现在与近端宿主轴突融合后立即电生理恢复，并在横断后24周(延迟神经融合后4周)改善轴突成熟和肌肉再神经支配。这些发现表明，TE-NMI具有改善延迟神经修复后功能恢复的潜力。组织工程神经肌肉接口(TE-NMI)是为局部传递外源性轴突而设计的神经元结构。TE-NMI是由保护性生物围栏内的长轴索横跨的离散神经元群体组成的。TE-NMI轴突穿过原本已失神经的神经鞘，“照看”远端路径和肌肉。TE-NMI轴突可以与残留的宿主近端轴突融合，以便立即进行电重新连接和诱发运动反应。TE-NMI可以在延迟神经修复之前防止长时间的失神经，并可能使延迟神经融合成为可能。
Nerve injury requiring surgical repair often results in poor functional recovery due to the inability of host axons to re-grow long distances and reform meaningful connections with the target muscle. While surgeons can re-route local axon fascicles to the target muscle, there are no technologies to provide an exogenous source of axons without sacrificing healthy nerves. Accordingly, we have developed tissue engineered neuromuscular interfaces (TE-NMIs) as the first injectable microtissue containing motor and sensory neurons in an anatomically-inspired architecture. TE-NMIs provide axon tracts that are intended to integrate with denervated distal structures and preserve regenerative capacity during prolonged periods without host innervation. Following implant, we found that TE-NMI axons promoted Schwann cell maintenance, integrated with distal muscle, and preserved an evoked muscle response out to 20-weeks post nerve transection in absence of innervation from host axons. By repopulating the distal sheath with exogenous axons, TE-NMIs also enabled putative delayed fusion with proximal host axons, a phenomenon previously not achievable in delayed repair scenarios due to distal axon degeneration. Here, we found immediate electrophysiological recovery after fusion with proximal host axons and improved axon maturation and muscle reinnervation at 24-weeks post-transection (4-weeks following delayed nerve fusion). These findings show that TE-NMIs provide the potential to improve functional recovery following delayed nerve repair. Tissue engineered neuromuscular interfaces (TE-NMIs) are neuronal constructs designed for local delivery of exogenous axons. TE-NMIs are comprised of discrete neuronal populations spanned by long axonal tracts within a protective bioencasement. TE-NMI axons extend through otherwise denervated nerve sheath to “babysit” the distal pathway and muscle. TE-NMI axons may fuse to residual host proximal axons for immediate electrical reconnection and evoked motor response. TE-NMIs may prevent prolonged denervation prior to delayed nerve repair and potentially enable delayed nerve fusion.
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DOI：
10.1083/jcb.201205025
发表时间：
2012-07-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Fontana X;Hristova M;Da Costa C;Patodia S;Thei L;Makwana M;Spencer-Dene B;Latouche M;Mirsky R;Jessen KR;Klein R;Raivich G;Behrens A
通讯作者：
Behrens A
影响因子：
5.7
作者：
Katiyar, Kritika S.;Struzyna, Laura A.;Cullen, D. Kacy
通讯作者：
Cullen, D. Kacy
影响因子：
--
作者：
Evans, GRD
通讯作者：
Evans, GRD
影响因子：
4.1
作者：
Cullen, D. Kacy;Tang-Schomer, Min D.;Smith, Douglas H.
通讯作者：
Smith, Douglas H.
影响因子：
4.2
作者：
Bittner GD;Sengelaub DR;Trevino RC;Ghergherehchi CL;Mikesh M
通讯作者：
Mikesh M