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Auto-Allo Graft Parallel Juxtaposition for Improved Neuroregeneration in Peripheral Nerve Reconstruction Based on Acellular Nerve Allografts

Boriani, Filippo MD, PhD*; Savarino, Lucia BSc; Fazio, Nicola PhD; Pedrini, Francesca Alice MD; Fini, Milena MD; Nicoli Aldini, Nicolò MD; Martini, Lucia DVM; Zini, Nicoletta BSc§,∥; Bernardini, Marco DVM; Bolognesi, Federico MD#; Marchetti, Claudio MD#; Baldini, Nicola MD*,†

doi: 10.1097/SAP.0000000000001900
Peripheral Nerve Surgery and Research

Introduction Nerve repair poses a significant surgical challenge, and much research on this topic for improvement in reconstruction of segmental defects is ongoing. The aims of the study were to reconfirm the accuracy and safety of a previously described nerve decellularization method on a larger experimental population of rabbits, as well as on human nerves, and to establish in vivo the efficacy of a new-concept mixed graft, comprising autologous and acellular nerve allograft components within the same graft.

Methods Acellular nerve allografts were implanted into tibial nerve defects of 5 rabbits (group A), autografts were implanted, representing the criterion standard, in other 5 animals (group B), and the innovative technique was used in the remaining 5 (group C). Twelve weeks postoperatively, nerve conduction evaluations were performed; animals were euthanatized, and grafts were harvested and morphologically, histomorphometrically, and immunohistochemically analyzed. Eventually, a preliminary in vitro validation of the decellularization method was performed on human nerves from a cadaver.

Results No clinical adverse effect was revealed during all the experimental times. No tissue reaction was observed, and in all groups, regenerated fascicles and bundles were shown by histology. However, both histology and histomorphometry demonstrated a better regenerative efficiency in group C. The morphological evaluation of the human nerve treated with the novel method showed complete decellularization.

Conclusion The microsurgical combined model demonstrated a better neuroregeneration than did pure autografts and acellular nerve allografts. The decellularization method seemed effective also on human nerves. Deeper investigations are necessary to further validate and transfer this new encouraging protocol to the clinical arena.

From the *Department of Biomedical and Neuromotor Sciences, University of Bologna

Orthopaedic Pathophysiology and Regenerative Medicine Unit

Laboratory of Preclinical and Surgical Studies, IRCCS Istituto Ortopedico Rizzoli

§CNR—National Research Council of Italy, Institute of Molecular Genetics

IRCCS Istituto Ortopedico Rizzoli, Bologna

Department of Animal Medicine, Production and Health, Padova University, Padua

#Department of Maxillofacial Surgery, University of Bologna, Bologna, Italy.

Received September 21, 2018, and accepted for publication, after revision January 28, 2019.

Conflicts of interest and sources of funding: This work was partially funded by the “Fondazione del Monte di Bologna e Ravenna” (F.B.), the Italian Ministry of Health “Ricerca Corrente” (N.B.), and “5 per mille 2015” for Health Research (Baldini). The authors declare no conflict of interest.

Reprints: Filippo Boriani, MD, PhD, Viale Aldini, 23, 40136 Bologna, Italy. E-mail:

Online date: June 20, 2019

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