title: The proximal medial sural nerve biopsy model: a standardised and reproducible baseline clinical model for the translational evaluation of bioengineered nerve guides.
abstract: Autologous nerve transplantation (ANT) is the clinical gold standard for the reconstruction of peripheral nerve defects. A large number of bioengineered nerve guides have been tested under laboratory conditions as an alternative to the ANT. The step from experimental studies to the implementation of the device in the clinical setting is often substantial and the outcome is unpredictable. This is mainly linked to the heterogeneity of clinical peripheral nerve injuries, which is very different from standardized animal studies. In search of a reproducible human model for the implantation of bioengineered nerve guides, we propose the reconstruction of sural nerve defects after routine nerve biopsy as a first or baseline study. Our concept uses the medial sural nerve of patients undergoing diagnostic nerve biopsy (≥ 2 cm). The biopsy-induced nerve gap was immediately reconstructed by implantation of the novel microstructured nerve guide, Neuromaix, as part of an ongoing first-in-human study. Here we present (i) a detailed list of inclusion and exclusion criteria, (ii) a detailed description of the surgical procedure, and (iii) a follow-up concept with multimodal sensory evaluation techniques. The proximal medial sural nerve biopsy model can serve as a preliminary nature of the injuries or baseline nerve lesion model. In a subsequent step, newly developed nerve guides could be tested in more unpredictable and challenging clinical peripheral nerve lesions (e.g., following trauma) which have reduced comparability due to the different nature of the injuries (e.g., site of injury and length of nerve gap).
authors.affiliation: Department of Plastic Surgery, Reconstructive and Hand Surgery, Burn Centre, Medical Faculty, RWTH Aachen University Hospital, Pauwelsstraße 30, 52074 Aachen, Germany.
authors.forename: Ahmet
authors.identifier: 0000-0002-2449-4776
authors.initials: A
authors.lastname: Bozkurt
authors.affiliation: Department of Plastic Surgery, Reconstructive and Hand Surgery, Burn Centre, Medical Faculty, RWTH Aachen University Hospital, Pauwelsstraße 30, 52074 Aachen, Germany.
authors.forename: Sabien G A
authors.initials: SG
authors.lastname: van Neerven
authors.affiliation: Department of Neurology, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany ; Institute of Neuropathology, RWTH Aachen University Hospital, 52074 Aachen, Germany ; JARA, Translational Brain Medicine, 52074 Aachen, Germany.
authors.forename: Kristl G
authors.initials: KG
authors.lastname: Claeys
authors.affiliation: Department of Plastic Surgery, Reconstructive and Hand Surgery, Burn Centre, Medical Faculty, RWTH Aachen University Hospital, Pauwelsstraße 30, 52074 Aachen, Germany.
authors.forename: Dan Mon
authors.initials: DM
authors.lastname: O'Dey
authors.affiliation: Clinical Trial Center Aachen (CTC-A), Medical Faculty, RWTH Aachen University Hospital, 52074 Aachen, Germany.
authors.forename: Angela
authors.identifier: 0000-0002-8294-435X
authors.initials: A
authors.lastname: Sudhoff
authors.affiliation: Institute of Neuropathology, RWTH Aachen University Hospital, 52074 Aachen, Germany ; JARA, Translational Brain Medicine, 52074 Aachen, Germany.
authors.forename: Gary A
authors.initials: GA
authors.lastname: Brook
authors.affiliation: Institute of Neuropathology, RWTH Aachen University Hospital, 52074 Aachen, Germany ; JARA, Translational Brain Medicine, 52074 Aachen, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Sellhaus
authors.affiliation: Department of Neurology, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany ; JARA, Translational Brain Medicine, 52074 Aachen, Germany ; Clinical Trial Center Aachen (CTC-A), Medical Faculty, RWTH Aachen University Hospital, 52074 Aachen, Germany.
authors.forename: Jörg B
authors.initials: JB
authors.lastname: Schulz
authors.affiliation: Institute of Neuropathology, RWTH Aachen University Hospital, 52074 Aachen, Germany ; JARA, Translational Brain Medicine, 52074 Aachen, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Weis
authors.affiliation: Department of Plastic Surgery, Reconstructive and Hand Surgery, Burn Centre, Medical Faculty, RWTH Aachen University Hospital, Pauwelsstraße 30, 52074 Aachen, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Pallua
mesh_terms: D000368:Aged; D057005:Bioengineering / Q000379:methods* / Q000592:standards*; D001706:Biopsy; D005260:Female; D048091:Guided Tissue Regeneration / Q000379:methods* / Q000592:standards*; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008297:Male; D008855:Microscopy, Electron, Scanning; D008875:Middle Aged; D008954:Models, Biological; D009443:Neuritis / Q000473:pathology; D015203:Reproducibility of Results; D013497:Sural Nerve / Q000473:pathology* / Q000601:surgery*; D014945:Wound Healing