Development and characterization of a predictive microCT-based non-union model in Fischer F344 rats.


Journal

Archives of orthopaedic and trauma surgery
ISSN: 1434-3916
Titre abrégé: Arch Orthop Trauma Surg
Pays: Germany
ID NLM: 9011043

Informations de publication

Date de publication:
Apr 2022
Historique:
received: 21 06 2020
accepted: 28 10 2020
pubmed: 12 11 2020
medline: 18 3 2022
entrez: 11 11 2020
Statut: ppublish

Résumé

Non-unions remain a clinical problem and are characterised by the failure to heal after a defined period of time. Current preclinical non-union models apply a wide variety of techniques to diminish intrinsic healing potential deviating from the clinical situation. The aim of this study was to develop and characterise a non-union model in rats using internal plate fixation without the need for additional healing insults, whereby bone healing can be longitudinally assessed using microCT. It was hypothesized that healing/non-unions can be accurately predicted at early time points by microCT. Female, skeletally mature Fischer F344 rats received a 2 mm or 1 mm femoral osteotomy, stabilized with either a 2 mm thick plate or a 1.25 mm thick plate. Healing was monitored by microCT over 14 weeks and histological analysis at euthanasia. The mechanical environment was characterised using finite element (FE) modelling and biomechanical testing. The majority of animals receiving the 2 mm thick plate displayed poor healing responses in both the 2 mm and 1 mm defect size groups. Bone and cartilage formation were markedly improved using the 1.25 mm thick plate. MicroCT could accurately predict bone forming capacity at early time points (3-4 weeks). The 2 mm thick plating system confers poor healing responses in female Fischer F344 rats, comparable to atrophic non-unions. By reducing plate thickness to increase interfragmentary strain within the defect site healing is improved, leading to borderline healing situations or increased abundance of cartilage tissue present in the defect site with ultimate failure to bridge the defect (hypertrophic non-union). Furthermore, microCT can reliably identify delayed/non-healing animals within 4 weeks, thereby allowing their selective targeting for the testing of novel, clinically relevant treatment strategies in different clinical situations aimed at restoring impaired bone healing.

Identifiants

pubmed: 33174612
doi: 10.1007/s00402-020-03680-4
pii: 10.1007/s00402-020-03680-4
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

579-590

Informations de copyright

© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.

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Auteurs

M Hildebrand (M)

AO Research Institute Davos, Clavadelerstrasse 8, 7270, Davos-Platz, Switzerland.

M Herrmann (M)

AO Research Institute Davos, Clavadelerstrasse 8, 7270, Davos-Platz, Switzerland.
IZKF Research Group Tissue Regeneration in Musculoskeletal Diseases, University Hospital Würzburg and Orthopedic Center for Musculoskeletal Research, University of Würzburg, Würzburg, Germany.

F Gieling (F)

AO Research Institute Davos, Clavadelerstrasse 8, 7270, Davos-Platz, Switzerland.

D Gehweiler (D)

AO Research Institute Davos, Clavadelerstrasse 8, 7270, Davos-Platz, Switzerland.

D Mischler (D)

AO Research Institute Davos, Clavadelerstrasse 8, 7270, Davos-Platz, Switzerland.

S Verrier (S)

AO Research Institute Davos, Clavadelerstrasse 8, 7270, Davos-Platz, Switzerland.

M Alini (M)

AO Research Institute Davos, Clavadelerstrasse 8, 7270, Davos-Platz, Switzerland.

S Zeiter (S)

AO Research Institute Davos, Clavadelerstrasse 8, 7270, Davos-Platz, Switzerland.

K Thompson (K)

AO Research Institute Davos, Clavadelerstrasse 8, 7270, Davos-Platz, Switzerland. keith.thompson@aofoundation.org.

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