Axonova Medical

Axonova Medical

https://axonovamed.com/

Functional restoration following major peripheral nerve injury (PNI) is challenging, given slow axon growth rates and eventual regenerative pathway degradation in the absence of axons. Smith et al. from the Center for Brain Injury and Repair, Department of Neurosurgery, Perelman School of MedicineAxonova Medical are developing tissue-engineered nerve grafts (TENGs) to simultaneously “bridge” missing nerve segments and “babysit” regenerative capacity by providing living axons to guide host axons and maintain the distal pathway. TENGs were biofabricated using porcine neurons 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 pigs. TENG axons also closely interacted with host Schwann cells 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 1).


Burrell JC, Das S, Laimo FA, Katiyar KS, Browne KD, Shultz RB, Tien VJ, Vu PT, Petrov D, Ali ZS, Rosen JM, Cullen DK. Engineered neuronal microtissue provides exogenous axons for delayed nerve fusion and rapid neuromuscular recovery in rats. Bioact Mater. 2022 Mar 24;18:339-353. doi: 10.1016/j.bioactmat.2022.03.018. PMID: 35415305; PMCID: PMC8965778.


Wofford KL, Shultz RB, Burrell JC, Cullen DK. Neuroimmune interactions and immunoengineering strategies in peripheral nerve repair. Prog Neurobiol. 2022 Jan;208:102172. doi: 10.1016/j.pneurobio.2021.102172. Epub 2021 Sep 4. PMID: 34492307; PMCID: PMC8712351.


Shultz RB, Katiyar KS, Laimo FA, Burrell JC, Browne KD, Ali ZS, Cullen DK. Biopreservation of living tissue engineered nerve grafts. J Tissue Eng. 2021 Aug 11;12:20417314211032488. doi: 10.1177/20417314211032488. PMID: 34394908; PMCID: PMC8361542.


O’Donnell JC, Purvis EM, Helm KVT, Adewole DO, Zhang Q, Le AD, Cullen DK. An implantable human stem cell-derived tissue-engineered rostral migratory stream for directed neuronal replacement. Commun Biol. 2021 Jul 15;4(1):879. doi: 10.1038/s42003-021-02392-8. PMID: 34267315; PMCID: PMC8282659.


Katiyar KS, Burrell JC, Laimo FA, Browne KD, Bianchi JR, Walters A, Ayares DL, Smith DH, Ali ZS, Ledebur HC, Cullen DK. Biomanufacturing of Axon-Based Tissue Engineered Nerve Grafts Using Porcine GalSafe Neurons. Tissue Eng Part A. 2021 Oct;27(19-20):1305-1320. doi: 10.1089/ten.TEA.2020.0303. Epub 2021 Apr 9. PMID: 33514288; PMCID: PMC8610031.


1)

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 grafts exploit axon-facilitated axon regeneration and pathway protection to enable recovery after 5-cm nerve defects in pigs. Sci Adv. 2022 Nov 4;8(44):eabm3291. doi: 10.1126/sciadv.abm3291. Epub 2022 Nov 4. PMID: 36332027.

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