Cited by 19Tissue Engineering and Regenerative MedicineNerve injury and regenerationElectrospun Nanofibers in Biomedical Applications

Effective decellularization of human nerve matrix for regenerative medicine with a novel protocol

Nieto-Nicolau, N, López-Chicón, P, Fariñas, O, Bolívar, S, Udina, E, Navarro, X, Casaroli-Marano, RP, Vilarrodona, A·2021·Cell and Tissue Research

Abstract

Injuries to the peripheral nerves represent a frequent cause of permanent disability in adults. The repair of large nerve lesions involves the use of autografts, but they have several inherent limitations. Overcoming these limitations, the use of decellularized nerve matrix has emerged as a promising treatment in tissue regenerative medicine. Here, we generate longer human decellularized nerve segments with a novel decellularization method, using nonionic, zwitterionic, and enzymatic incubations. Efficiency of decellularization was measured by DNA quantification and cell remnant analysis (myelin, S100, neurofilament). The evaluation of the extracellular matrix (collagen, laminin, and glycosaminoglycans) preservation was carried out by enzyme-linked immunosorbent assay (ELISA) or biochemical methods, along with histological and immunofluorescence analysis. Moreover, biomechanical properties and cytocompatibility were tested. Results showed that the decellularized nerves generated with this protocol have a concentration of DNA below the threshold of 50 ng/mg of dry tissue. Furthermore, myelin, S100, and MHCII proteins were absent, although some neurofilament remnants could be observed. Moreover, extracellular matrix proteins were well maintained, as well as the biomechanical properties, and the decellularized nerve matrix did not generate cytotoxicity. These results show that our method is effective for the generation of decellularized human nerve grafts. The generation of longer decellularized nerve segments would allow the understanding of the regenerative neurobiology after nerve injuries in both clinical assays and bigger animal models. Effective decellularization of human nerve matrix for regenerative medicine with a novel protocol. Combination of zwitterionic, non-ionic detergents, hyperosmotic solution and nuclease enzyme treatment remove cell remnants, maintain collagen, laminin and biomechanics without generating cytotoxic leachables.

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Crossref · 10.1007/s00441-020-03317-3

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Authors
Nieto-Nicolau, N., López-Chicón, P., Fariñas, O., Bolívar, S., Udina, E., Navarro, X., Casaroli-Marano, R., & Vilarrodona, A.
Affiliations
  • Universitat Autònoma de Barcelona (ES)
  • Banc de Sang i Teixits (ES)
Venue
Cell and Tissue Research
Published
2021-01-20
Volume
384
Issue
1
Pages
167-177
ISSN
  • 0302-766X (ISSN-L)
  • 1432-0878
OpenAlex
W3122573850
Cited by
19
References
46
Citations by year
2026: 1 · 2025: 4 · 2024: 6 · 2023: 2 · 2022: 4 · 2021: 2
FWCI
3.31
Type
journal article
Language
en
Open access
closed
Locations
  • Cell and Tissue Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • TERCEL (RD16/0011/0035)
  • CIBERNED (CB06/05/1105)
  • Banc de Sang i Teixits (Ref I.2017.056)
Topics
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
  • Physical Sciences › Materials Science › Biomaterials › Electrospun Nanofibers in Biomedical Applications
Keywords
decellularization, peripheral nerve injury, nerve grafts, zwitterionic detergents, nonionic detergents, enzymatic treatment, extracellular matrix preservation, collagen, laminin, tissue mechanics, cytocompatibility, cell-free scaffolds
MeSH terms
Extracellular Matrix, Humans, Nerve Tissue, Regenerative Medicine

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