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The biomaterial-mediated healing of critical size bone defects in the ovariectomized rat

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Abstract

Summary

This study demonstrated an impaired biomaterial-mediated bone regeneration in a critical sized calvarial defect established within an ovariectomized rat model. Histological and microtomographic evidences were supported by an impaired osteoblastic gene expression and altered expression of estrogen receptors and adipogenic markers.

Introduction

This work aims to address the bone regeneration process in the ovariectomized rat model, by assessing a calvarial critical size defect implanted with a biocompatible bovine bone mineral graft.

Methods

Animals were randomly divided into two groups: Ovx (bilateral ovariectomy) and Sham (control surgery). Following 8 weeks, all animals were submitted to a surgical bicortical craniotomy (5-mm circular critical size defect), which was filled with a biocompatible mineral graft. Animals were euthanized at 1, 3, and 6 months following graft implantation (n = 10), and results on the orthotopic bone regeneration process were blindly evaluated by radiographic, microtomographic, histological, histomorphometric, and gene expression techniques.

Results

In the attained model, in both Sham and Ovx groups, the bone regenerative process was found to occur in a slow-paced manner. Likewise, a qualitative evaluation of the microtomographic and histological analysis, as well as quantitative data from histomorphometric indexes, revealed reduced bone regeneration in Ovx animals, at the assayed time points. Significant differences were attained at the 3 and 6 months. Gene expression analysis revealed a reduced expression of osteoblastic-related genes and an altered expression of estrogen receptors and adipogenic markers, within the regenerating bone of Ovx animals.

Conclusions

Due to the similarities between the osteoporotic animal model and the human condition of postmenopausal osteoporosis, it might be relevant to consider the potential clinical implication of the osteoporotic condition in the biomaterial-mediated bone tissue healing/regeneration process.

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Acknowledgments

Financial support from the Fundação para a Ciência e Tecnologia (FCT), project PTDC/DES/103047/2008, is greatly acknowledged.

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Surgery Department, Faculty of Dental Medicine, University of Porto, Rua Dr. Manuel Pereira da Silva, 4200-393, Porto, Portugal

    S. F. Durão & A. C. Felino

  2. Laboratory for Bone Metabolism and Regeneration, Faculty of Dental Medicine, University of Porto, Rua Dr. Manuel Pereira da Silva, 4200-393, Porto, Portugal

    P. S. Gomes, J. C. Silva & M. H. Fernandes

  3. Department of Zootechny, Center for the Study of Animal Sciences (CECA), ECAV, University de Trás-os-Montes e Alto Douro, 5001-801, Vila Real, Portugal

    B. J. Colaço

  4. Biochemistry Department, Faculty of Sports, University of Porto, Rua Dr. Plácido Costa, 91, 4200-450, Porto, Portugal

    H. M. Fonseca & J. R. Duarte

  5. MedInUP - Center for Drug Discovery and Innovative Medicines, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319, Porto, Portugal

    P. S. Gomes & M. H. Fernandes

Authors
  1. S. F. Durão
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Correspondence to P. S. Gomes.

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ESM 1

Surgical craniotomy and graft implantation. a Exposure of the calvarial bone; b establishment of the standardized bicortical critical size calvarial defect; c graft implantation; d closure of the surgical wound (JPEG 101 kb)

High resolution image (TIFF 1682 kb)

ESM 2

Characterization of the osteoporotic conditions (n = 10). a Weight of Sham and Ovx animals throughout the healing period following craniotomy; b weight of the uteri from Sham and Ovx animals throughout the healing period following craniotomy; c representative 3D renderings of 6-month Sham animals, showing the analyzed volume of interest in the proximal tibia. Scale bar represents 1 mm; d representative 3D renderings of 6-month Ovx animals, showing the analyzed volume of interest in the proximal tibia. Scale bar represents 1 mm; e microstructural parameters of the trabecular structure of the proximal tibia in Sham and Ovx animals at the 6-month time point. Asterisk—significantly different from the Sham group (JPEG 84 kb)

High resolution image (TIFF 415 kb)

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Durão, S.F., Gomes, P.S., Colaço, B.J. et al. The biomaterial-mediated healing of critical size bone defects in the ovariectomized rat. Osteoporos Int 25, 1535–1545 (2014). https://doi.org/10.1007/s00198-014-2656-y

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  • DOI: https://doi.org/10.1007/s00198-014-2656-y

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