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Sci Rep. 2018 Mar 14;8(1):4474. doi: 10.1038/s41598-018-22628-8.

Fetal extracellular matrix nerve wraps locally improve peripheral nerve remodeling after complete transection and direct repair in rat.

Author information

1
Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
2
McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
3
Swanson School of Engineering, Department of Bioengineering, Pittsburgh, PA, USA.
4
Department of Plastic Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
5
Plastic Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
6
Department of Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
7
VA Pittsburgh Healthcare System Pittsburgh, Pittsburgh, PA, USA.
8
Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. Stek0323@gmail.com.
9
McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA. Stek0323@gmail.com.
10
Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA. Stek0323@gmail.com.

Abstract

In peripheral nerve (PN) injuries requiring surgical repair, as in PN transection, cellular and ECM remodeling at PN epineurial repair sites is hypothesized to reduce PN functional outcomes by slowing, misdirecting, or preventing axons from regrowing appropriately across the repair site. Herein this study reports on deriving and analyzing fetal porcine urinary bladder extracellular matrix (fUB-ECM) by vacuum assisted decellularization, fabricating fUBM-ECM nerve wraps, and testing fUB-ECM nerve wrap biocompatibility and bioactivity in a trigeminal, infraorbital nerve (ION) branch transection and direct end-to-end repair model in rat. FUB-ECM nerve wraps significantly improved epi- and endoneurial organization and increased both neovascularization and growth associated protein-43 (GAP-43) expression at PN repair sites, 28-days post surgery. However, the number of neurofilament positive axons, remyelination, and whisker-evoked response properties of ION axons were unaltered, indicating improved tissue remodeling per se does not predict axon regrowth, remyelination, and the return of mechanoreceptor cortical signaling. This study shows fUB-ECM nerve wraps are biocompatible, bioactive, and good experimental and potentially clinical devices for treating epineurial repairs. Moreover, this study highlights the value provided by precise, analytic models, like the ION repair model, in understanding how PN tissue remodeling relates to axonal regrowth, remyelination, and axonal response properties.

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