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
Abstract Although regeneration of damaged axons in peripheral nerves has long been observed, the mechanisms facilitating this growth are not well characterized. Recently, we demonstrated that host axon regeneration could be greatly enhanced by transplanting engineered living axon tracts to guide outgrowth. Here, we used a model of rat sciatic nerve transection to explore potential mechanisms of this facilitated regeneration and its efficacy in comparison with nerve guidance tubes (NGTs) and autografts. Tissue engineered nerve grafts (TENGs) were developed via “stretch-growth” in mechanobioreactors and consisted of centimeter-scale aligned axonal tracts. Either TENGs, NGTs or autografts (reversed nerve) were then transplanted to bridge a 1 cm segmental gap in the sciatic nerve with the mechanisms of axonal regrowth assessed at 2 weeks and the extent of functional recovery assessed at 16 weeks. We observed numerous host axons growing directly along and intertwining with pre-formed axonal tracts in TENGs. This behavior appears to mimic the action of “pioneer” axons in developmental pathfinding by providing living cues for directed and accelerated outgrowth. Indeed, we found that the rates of axon regeneration were 3-4 fold faster than NGTs and equivalent to autografts. It was also observed that infiltration of host Schwann cells – traditional drivers of peripheral axon regeneration – was both accelerated and progressed directly along TENG axonal tracts. These TENG repairs resulted in levels of functional recovery equivalent to autografts, with each being several fold superior to NGT repairs. This new mechanism – which we term “axon-facilitated axon-regeneration” – may be further exploited to enhance axonal regeneration and functional recovery following neurotrauma.
Morand Joseph P.、Clements Basak、Katiyar Kritika S.、Browne Kevin D.、Ledebur Harry C.、Ali Zarina、Kohn Joachim、Burrell Justin C.、Smith Douglas H.、Cullen D. Kacy、Laimo Franco A.、Struzyna Laura A.
Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of PennsylvaniaNew Jersey Center for Biomaterials, Rutgers UniversityCenter for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania||Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center||School of Biomedical Engineering, Science & Health Systems, Drexel University||Axonova Medical, LLCCenter for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania||Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical CenterAxonova Medical, LLCCenter for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of PennsylvaniaNew Jersey Center for Biomaterials, Rutgers UniversityCenter for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania||Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center||Department of Bioengineering, School of Engineering & Applied Science, University of PennsylvaniaCenter for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania||Axonova Medical, LLCCenter for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania||Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center||Department of Bioengineering, School of Engineering & Applied Science, University of Pennsylvania||Axonova Medical, LLCCenter for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania||Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical CenterCenter for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania||Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center||Department of Bioengineering, School of Engineering & Applied Science, University of Pennsylvania
神经病学、精神病学基础医学生物工程学
Morand Joseph P.,Clements Basak,Katiyar Kritika S.,Browne Kevin D.,Ledebur Harry C.,Ali Zarina,Kohn Joachim,Burrell Justin C.,Smith Douglas H.,Cullen D. Kacy,Laimo Franco A.,Struzyna Laura A..Tissue Engineered Axon Tracts Serve as Living Scaffolds to Accelerate Axonal Regeneration and Functional Recovery Following Peripheral Nerve Injury in Rats[EB/OL].(2025-03-28)[2025-05-02].https://www.biorxiv.org/content/10.1101/654723.点此复制
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