Tissue Engineered Axon Tracts Serve as Living Scaffolds to Accelerate Axonal Regeneration and Functional Recovery Following Peripheral Nerve Injury in Rats
Tissue Engineered Axon Tracts Serve as Living Scaffolds to Accelerate Axonal Regeneration and Functional Recovery Following Peripheral Nerve Injury in Rats
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DOI：
10.3389/fbioe.2020.00492
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发表时间：
2020-05-25
影响因子：
5.7
通讯作者：
Cullen, D. Kacy
中科院分区：
文献类型：
--
作者：
Katiyar, Kritika S.;Struzyna, Laura A.;Cullen, D. Kacy
加快轴突再生速度的策略将促进周围神经损伤后的功能恢复，特别是对于涉及节段性神经缺陷的病例。我们正在推进组织工程神经移植物(TENG)，它由长的、排列的、厘米级的轴突束组成，由定制的机械反应器中的轴突“拉伸生长”控制过程开发而成。本研究使用大鼠坐骨神经模型，研究了TIGGS桥接神经间隙的轴突再生机制，以及与神经引导管(NGT)或自体移植相比，功能恢复的程度。我们证实，宿主轴突的生长直接发生在腾氏轴突上，通过提供加速生长的直接线索，模拟了发育过程中“先锋”轴突的行为。事实上，横跨TNG的轴突再生速度比NGT快3-4倍，相当于自体移植。宿主雪旺细胞--外周轴突再生的传统驱动因素--的渗透也被加速，并直接沿着Teng轴突进行。此外，Teng修复导致的功能恢复水平相当于自体移植，两者都比NGTS高出几倍。这些发现表明，工程化轴突束可以作为“活的支架”，通过一种新的机制来引导宿主轴突生长--我们称之为“轴突促进轴突再生”--这种机制可以促进功能恢复。
Strategies to accelerate the rate of axon regeneration would improve functional recovery following peripheral nerve injury, in particular for cases involving segmental nerve defects. We are advancing tissue engineered nerve grafts (TENGs) comprised of long, aligned, centimeter-scale axon tracts developed by the controlled process of axon "stretch-growth" in custom mechanobioreactors. The current study used a rat sciatic nerve model to investigate the mechanisms of axon regeneration across nerve gaps bridged by TENGs as well as the extent of functional recovery compared to nerve guidance tubes (NGT) or autografts. We established that host axon growth occurred directly along TENG axons, which mimicked the action of "pioneer" axons during development by providing directed cues for accelerated outgrowth. Indeed, axon regeneration rates across TENGs were 3-4 fold faster than NGTs and equivalent to autografts. The infiltration of host Schwann cells - traditional drivers of peripheral axon regeneration - was also accelerated and progressed directly along TENG axons. Moreover, TENG repairs resulted in functional recovery levels equivalent to autografts, with both several-fold superior to NGTs. These findings demonstrate that engineered axon tracts serve as "living scaffolds" to guide host axon outgrowth by a new mechanism - which we term "axon-facilitated axon regeneration" - that leads to enhanced functional recovery.