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Peripheral Nerve Regeneration

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Front. Cell. Neurosci. | doi: 10.3389/fncel.2018.00501

In vivo evaluation of nanostructured fibrin-agarose hydrogels with mesenchymal stem cells for peripheral nerve repair

 Jesús Chato-Astrain1,  Fernando Campos1*, Olga Roda2, Esther Miralles3, Daniel Durand-Herrera1, José Antonio Sáez-Moreno3, Salomé García-García3, Miguel Alaminos1, Antonio Campos1 and  Víctor Carriel1, 4*
  • 1Departamento de Histologia, Universidad de Granada, Spain
  • 2Departamento de Anatomía y Embriología Humana, Facultad de Medicina, Universidad de Granada, Spain
  • 3División de Neurofisiología Clínica, Hospital Universitario Virgen de las Nieves, Spain
  • 4University of Granada, Spain

The regenerative capability of peripheral nerves is very limited, and several strategies have been proposed to increase nerve regeneration. In the present work, we have analyzed the in vivo usefulness of a novel nanostructured fibrin-agarose bio-artificial nerve substitute (Nano) used alone or in combination with NeuraGen® collagen type I conduits (Coll-Nano) in laboratory rats with a 10-mm sciatic nerve defect. Control animals were subjected to the gold-standard autograft technique (Auto). Results first demonstrated that the percentage of self-amputations was lower in Nano and Coll-Nano groups as compared to the Auto group. Neurotrophic ulcers were more abundant in the Auto group (60%, with 66.6% of them being >2mm) than Nano and Coll-Nano groups (0%) at 4 weeks, although Nano showed more ulcers after 12-weeks. Foot length was significantly altered in Auto animals due to neurogenic retraction, but not in Nano and Coll-Nano groups after 12-weeks. At the functional level, all animals showed a partial sensory recovery as determined by the pinch test, especially in Nano and Auto groups, but did not reach the levels of native animals. Toe-spread test revealed a partial motor function recovery only in Nano animals at 4-weeks and Auto and Nano at 12-weeks. Electromyography showed clear denervation signs in all experimental groups, with few differences between Auto and Nano animals. After 12-weeks, an important denervation decrease and an increase of the reinnervation process was found in Auto and Nano groups, with no differences between these groups. Histological analyses demonstrated an active peripheral nerve regeneration process with newly-formed peripheral nerve fascicles showing S-100, GAP-43 and myelin in all experimental groups. The peripheral nerve regeneration process was more abundant in Auto group, followed by Nano group, and both were better than Coll-Nano group. Muscle histology confirmed the electromyography results and showed some atrophy and fibrosis signs and an important weight and volume loss in all groups, especially in the Coll-Nano group (56.8% weight and 60.4% volume loss). All these results suggest that the novel Nano substitutes used in in vivo were able to contribute to bridge a 10-mm peripheral nerve defect in rats.

Keywords: Peripheral nerve repair, Neural tissue engineering (NTE), fibrin-agarose hydrogels, in vivo, Mesenchymal Stem Cells, Histology

Received: 28 Sep 2018; Accepted: 04 Dec 2018.

Edited by:

Stefania Raimondo, Dipartimento di Scienze Cliniche e Biologiche, Università di Torino, Italy

Reviewed by:

Chiara Tonda-Turo, Politecnico di Torino, Italy
Ana Colette Maurício, Abel Salazar Institute of Biomedical Sciences, University of Porto, Portugal  

Copyright: © 2018 Chato-Astrain, Campos, Roda, Miralles, Durand-Herrera, Sáez-Moreno, García-García, Alaminos, Campos and Carriel. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Fernando Campos, Departamento de Histologia, Universidad de Granada, Granada, Spain,
Prof. Víctor Carriel, University of Granada, Granada, Spain,