Development of vascularized nerve scaffold using perfusion-decellularization and recellularization

Wüthrich, Tsering; Lese, Ioana; Haberthür, David; Zubler, Cédric; Hlushchuk, Ruslan; Hewer, Ekkehard; Maistriaux, Louis; Gianello, Pierre; Lengelé, Benoît; Rieben, Robert; Vögelin, Esther; Olariu, Radu; Duisit, Jérôme; Taddeo, Adriano (2020). Development of vascularized nerve scaffold using perfusion-decellularization and recellularization. Materials science & engineering C, 117(111311), p. 111311. Elsevier 10.1016/j.msec.2020.111311

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Introduction
Vascularized nerve grafts (VNG) may offer an advantage in peripheral nerve regeneration by avoiding ischemic damage and central necrosis observed in non-VNG, particularly for the treatment of large and long nerve defects. However, surgical complexity, donor site morbidity and limited nerve availability remain important drawbacks for the clinical use of VNG. Here we explore the potential of perfusion-decellularization for bioengineering a VNG to be used in peripheral nerve reconstruction.

Methods
Porcine sciatic nerves were surgically procured along with their vascular pedicle attached. The specimens were decellularized via perfusion-decellularization and preservation of the extracellular matrix (ECM), vascular patency and tissue cytokine contents were examined. Scaffold reendothelialization was conducted with porcine aortic endothelial cells in a perfusion-bioreactor.

Results
Morphologic examination of decellularized VNG and analysis of the DNA content demonstrated cell clearance whereas ECM content and structures of the nerve fascicles were preserved. Using 3D micro-computed tomography imaging we observed optimal vasculature preservation in decellularized scaffolds, down to the capillary level. Cytokine quantification demonstrated measurable levels of growth factors after decellularization. Endothelial cell engraftment of the large caliber vessels was observed in reendothelialized scaffolds.

Conclusions
In this study we provide evidence that perfusion-decellularization can be used to create vascularized nerve scaffolds in which the vasculature and the ECM component are well preserved. As compared to non-vascularized conduits, engineered vascularized nerve scaffolds may represent an ideal approach for promoting better nerve regeneration in larger nerve defect reconstructions.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Orthopaedic, Plastic and Hand Surgery (DOPH) > Clinic of Plastic and Hand Surgery > Plastic, Reconstructive and Aesthetic Surgery
04 Faculty of Medicine > Department of Orthopaedic, Plastic and Hand Surgery (DOPH) > Clinic of Plastic and Hand Surgery > Hand Surgery
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Topographical and Clinical Anatomy
04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Department of Orthopaedic, Plastic and Hand Surgery (DOPH) > Clinic of Plastic and Hand Surgery
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Handchirurgie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Plastische Chirurgie

UniBE Contributor:

Lese, Ioana; Haberthür, David; Zubler, Cédric Olivier; Hlushchuk, Ruslan; Hewer, Ekkehard; Rieben, Robert; Vögelin, Esther and Olariu, Radu

Subjects:

600 Technology > 630 Agriculture
600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

0928-4931

Publisher:

Elsevier

Language:

English

Submitter:

David Christian Haberthür

Date Deposited:

17 Aug 2020 15:26

Last Modified:

29 Sep 2020 11:12

Publisher DOI:

10.1016/j.msec.2020.111311

PubMed ID:

32919672

BORIS DOI:

10.7892/boris.145960

URI:

https://boris.unibe.ch/id/eprint/145960

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