====== Tissue-engineered nerve graft ======

Surgical [[repair]] for severe [[peripheral nerve injury treatment]] represents not only a pressing medical need but also a great clinical [[challenge]]. [[Autologous nerve graft]]ing remains a [[gold standard]] for bridging an extended gap in transected nerves. The formidable limitations related to this approach, however, have evoked the development of tissue-engineered nerve grafts as a promising alternative to autologous nerve grafts. A [[tissue-engineered nerve graft]] is typically constructed through a combination of a neural [[scaffold]] and a variety of cellular and molecular components. The initial and basic structure of the neural scaffold that serves to provide mechanical guidance and an optimal environment for [[nerve regeneration]] was a single hollow [[nerve guidance conduit]]. Later there have been several improvements to the basic structure, especially the introduction of physical fillers into the lumen of a hollow nerve guidance conduit. Up to now, a diverse array of [[biomaterial]]s, either of natural or of synthetic origin, together with well-defined fabrication techniques, has been employed to prepare neural [[scaffold]]s with different structures and properties. Meanwhile different types of support cells and/or growth factors have been incorporated into the neural scaffold, producing unique biochemical effects on nerve regeneration and function restoration
((Gu X, Ding F, Yang Y, Liu J. Construction of [[tissue-engineered nerve graft]]s and their [[application]] in peripheral [[nerve regeneration]]. Prog Neurobiol. 2011 Feb;93(2):204-30. doi: 10.1016/j.pneurobio.2010.11.002. Epub 2010 Dec 2. PMID: 21130136.)).
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Functional [[restoration]] following major [[peripheral nerve injury]] (PNI) is challenging, given slow [[axon growth]] rates and eventual [[regenerative]] [[pathway]] [[degradation]] in the absence of [[axon]]s. Smith et al. from the Center for Brain Injury and Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, [[Philadelphia]]
[[Axonova Medical]] are developing [[tissue-engineered nerve graft]]s (TENGs) to simultaneously "bridge" missing [[nerve]] [[segment]]s and "babysit" regenerative capacity by providing living [[axon]]s to guide host axons and maintain the distal pathway. TENGs were biofabricated using [[porcine]] [[neuron]]s and "stretch-grown" axon tracts. TENG neurons survived and elicited axon-facilitated axon [[regeneration]] to accelerate regrowth across both short (1 cm) and long (5 cm) segmental nerve defects in [[pig]]s. TENG axons also closely interacted with host [[Schwann cell]]s to maintain pro-regenerative capacity. TENGs drove regeneration across 5-cm defects in both [[motor]] and mixed motor-sensory nerves, resulting in dense [[axon regeneration]] and electrophysiological recovery at levels similar to [[autograft]] repairs. This approach of accelerating axon regeneration while maintaining the pathway for long-distance regeneration may achieve recovery after currently unrepairable PNIs
((Smith DH, Burrell JC, Browne KD, Katiyar KS, Ezra MI, Dutton JL, Morand JP, Struzyna LA, Laimo FA, Chen HI, Wolf JA, Kaplan HM, Rosen JM, Ledebur HC, Zager EL, Ali ZS, Cullen DK. [[Tissue]]-engineered [[graft]]s exploit [[axon]]-facilitated [[axon regeneration]] and [[pathway]] protection to enable recovery after 5-cm nerve defects in [[pig]]s. Sci Adv. 2022 Nov 4;8(44):eabm3291. doi: 10.1126/sciadv.abm3291. Epub 2022 Nov 4. PMID: 36332027.)).