A new semi-orthotopic bone defect model for cell and biomaterial testing in regenerative medicine.

Animal model Bone Bone substitutes Endochondral ossification Guided tissue regeneration Tissue scaffolds

Journal

Biomaterials
ISSN: 1878-5905
Titre abrégé: Biomaterials
Pays: Netherlands
ID NLM: 8100316

Informations de publication

Date de publication:
12 2021
Historique:
received: 19 07 2021
revised: 08 10 2021
accepted: 14 10 2021
pubmed: 23 10 2021
medline: 15 12 2021
entrez: 22 10 2021
Statut: ppublish

Résumé

In recent decades, an increasing number of tissue engineered bone grafts have been developed. However, expensive and laborious screenings in vivo are necessary to assess the safety and efficacy of their formulations. Rodents are the first choice for initial in vivo screens but their size limits the dimensions and number of the bone grafts that can be tested in orthotopic locations. Here, we report the development of a refined murine subcutaneous model for semi-orthotopic bone formation that allows the testing of up to four grafts per mouse one order of magnitude greater in volume than currently possible in mice. Crucially, these defects are also "critical size" and unable to heal within the timeframe of the study without intervention. The model is based on four bovine bone implants, ring-shaped, where the bone healing potential of distinct grafts can be evaluated in vivo. In this study we demonstrate that promotion and prevention of ossification can be assessed in our model. For this, we used a semi-automatic algorithm for longitudinal micro-CT image registration followed by histological analyses. Taken together, our data supports that this model is suitable as a platform for the real-time screening of bone formation, and provides the possibility to study bone resorption, osseointegration and vascularisation.

Identifiants

pubmed: 34678648
pii: S0142-9612(21)00544-5
doi: 10.1016/j.biomaterials.2021.121187
pii:
doi:

Substances chimiques

Biocompatible Materials 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

121187

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

Auteurs

E Andrés Sastre (E)

Department of Oral and Maxillofacial Surgery, Erasmus University Medical Center, Rotterdam, the Netherlands.

Y Nossin (Y)

Department of Otorhinolaryngology, Erasmus University Medical Center, Rotterdam, the Netherlands.

I Jansen (I)

Department of Oral and Maxillofacial Surgery, Erasmus University Medical Center, Rotterdam, the Netherlands; Orthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands; Institute for Complex Molecular Systems, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.

N Kops (N)

Department of Orthopaedics and Sports Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.

C Intini (C)

Tissue Engineering Research Group, Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.

J Witte-Bouma (J)

Department of Oral and Maxillofacial Surgery, Erasmus University Medical Center, Rotterdam, the Netherlands.

B van Rietbergen (B)

Orthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands; Department of Orthopaedic Surgery, Research School CAPHRI, Maastricht University Medical Center, Maastricht, the Netherlands.

S Hofmann (S)

Orthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands; Institute for Complex Molecular Systems, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.

Y Ridwan (Y)

Department of Molecular Genetics, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.

J P Gleeson (JP)

Tissue Engineering Research Group, Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.

F J O'Brien (FJ)

Tissue Engineering Research Group, Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland; SFI Advanced Materials and Bioengineering Research (AMBER) Center, Royal College of Surgeons in Ireland and Trinity College Dublin, Dublin, Ireland; Trinity Center for Biomedical Engineering, Trinity College Dublin, Dublin, Ireland.

E B Wolvius (EB)

Department of Oral and Maxillofacial Surgery, Erasmus University Medical Center, Rotterdam, the Netherlands.

G J V M van Osch (GJVM)

Department of Otorhinolaryngology, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Orthopaedics and Sports Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Biomechanical Engineering, Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology, Delft, the Netherlands.

E Farrell (E)

Department of Oral and Maxillofacial Surgery, Erasmus University Medical Center, Rotterdam, the Netherlands. Electronic address: e.farrell@erasmusmc.nl.

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