Engineered neuronal microtissue provides exogenous axons for delayed nerve fusion and rapid neuromuscular recovery in rats.

Autor:	Burrell JC; Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Department of Bioengineering, School of Engineering & Applied Science, University of Pennsylvania, Philadelphia, PA, USA.; Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA, 19104, USA., Das S; Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA, 19104, USA., Laimo FA; Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA, 19104, USA., Katiyar KS; Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Axonova Medical, LLC, Philadelphia, PA, USA., Browne KD; Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA, 19104, USA., Shultz RB; Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Axonova Medical, LLC, Philadelphia, PA, USA., Tien VJ; Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Department of Bioengineering, School of Engineering & Applied Science, University of Pennsylvania, Philadelphia, PA, USA.; Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA, 19104, USA., Vu PT; Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Department of Bioengineering, School of Engineering & Applied Science, University of Pennsylvania, Philadelphia, PA, USA.; Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA, 19104, USA., Petrov D; Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Ali ZS; Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Rosen JM; Dartmouth-Hitchcock Medical Center, Division of Plastic Surgery, Dartmouth College, Lebanon, NH, USA., Cullen DK; Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Department of Bioengineering, School of Engineering & Applied Science, University of Pennsylvania, Philadelphia, PA, USA.; Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA, 19104, USA.; Axonova Medical, LLC, Philadelphia, PA, USA.
Jazyk:	angličtina
Zdroj:	Bioactive materials [Bioact Mater] 2022 Mar 24; Vol. 18, pp. 339-353. Date of Electronic Publication: 2022 Mar 24 (Print Publication: 2022).
DOI:	10.1016/j.bioactmat.2022.03.018
Abstrakt:	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. Competing Interests: D.K.C is a co-founder of Axonova Medical, LLC, and Innervace, Inc. which are University of Pennsylvania spin-out companies focused on translation of advanced regenerative therapies to treat nervous system disorders. Multiple patents relate to the composition, methods, and use of tissue engineered nervous tissue [U.S. Patent 9,895,399 (D.K.C.), U.S. Patent 10,525,085 (D.K.C.), U.S. Patent Application 16/753,634 (D.K.C), and U.S. Provisional Patent Application 62/937,489 (D.K.C. and J.C.B.)], microtissue-engineered neural networks [U.S. Patent Application 15/032,677 (D.K.C.), U.S. Patent Application 16/093,036 (D.K.C.), and U.S. Provisional Patent Application 63/209,639 (D.K.C., J.C.B., J.M.R.)], and innervated engineered tissue for organ modulation [U.S. Provisional Patent Application 62/758,203 (D.K.C. and S.D.)]. No other author has declared a potential conflict of interest. (© 2022 The Authors.)
Databáze:	MEDLINE
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