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Three-Dimensional Porous Gelapin–Simvastatin Scaffolds Promoted Bone Defect Healing in Rabbits

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Abstract

Treatment of large bone defects (LBDs) is technically demanding. Tissue engineering is an option. A bioactive graft may be produced by combining tissue scaffolds and healing promotive factors in order to accelerate bone repair. We investigated the role of Simvastatin (Sim)-embedded porous Gelapin (Gel) scaffold on experimental bone healing. At first, the effectiveness of different concentrations of Gel and Sim powders was investigated in an experimentally induced femoral hole model in rabbits (n = 6) for 30 days. Then bone bioactive grafts were produced by combination of the effective concentrations of Gel, Sim, and Genipin. The bioimplants were subcutaneously tested in a rabbit model (n = 9) to determine their biocompatibility and biodegradability for 10–30 days. Finally, a large radial bone defect model was produced in rabbits (n = 20), and the bioimplants were inserted in the defects. The untreated and autograft-treated bone defects were served as controls. The animals were euthanized after 30 and 60 days of bone injury. The bone samples were evaluated by radiography, three-dimensional CT scan, bone densitometry, histopathology, and nano-indentation. At a concentration of 5 mg/hole, Sim closed the femoral bone holes after 30 days, while in the defect, autograft, and Gel groups, the holes were open. Both the Gel and Gel–Sim scaffolds were biocompatible and biodegradable. Subcutaneously, the Gel–Sim scaffold was replaced with the newly regenerated ectopic bone after 30 days. After implantation of the Gel–Sim scaffold in the radial bone defects, the scaffold was completely replaced with new woven bone after 30 days which was then matured and remodeled into a cortical bone after 60 days. Sixty days after bone injury, the Gel–Sim-treated defects had significantly higher bone volume, matrix mineralization, elastic modulus, and contact hardness when compared to the controls. The Gel–Sim scaffold may be a suitable option in managing LBDs.

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Acknowledgments

The authors would like to thank the authorities of AJA University of Medical Sciences for providing the facilitations in performing the present investigation. The kind cooperation of Mr. A. Navideh (Department of Radiology), Mr. M. Chehri (Department of Pathology), Mr. S. Shirzadi (Animal Laboratory center), and Mr. M. Younesi (Department of Radiology, Faculty of Medicine, AJA, University of Medical Sciences, Tehran, Iran) is fully acknowledged.

Conflict of interest

This is the authors’ own work. Dr Ali Moshiri reports that neither conflict of interest nor financial disclosure is present associated with this work or its related contents. Dr Mostafa Shahrezaie reports that neither conflict of interest nor financial disclosure is present associated with this work or its related contents. Dr Babak Shekarchi reports that neither conflict of interest nor financial disclosure is present associated with this work or its related contents. Prof. Ahmad Oryan reports that neither conflict of interest nor financial disclosure is present associated with this work or its related contents. Dr. Kamran Azma reports that neither conflict of interest nor financial disclosure is present associated with this work or its related contents.

Human and Animal Rights and Informed Consent statement

All animals received humane care in compliance with the Guide for Care and use of Laboratory Animals (NIH publication No. 85–23, revised 1985). The study was approved by the local Ethics Committee of AJA University of Medical Science.

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Authors and Affiliations

  1. Department of Orthopedic Surgery, School of Medicine, AJA University of Medical Science, Tehran, Iran

    Ali Moshiri & Mostafa Shahrezaee

  2. Department of Radiology, School of Medicine, AJA University of Medical Science, Tehran, Iran

    Babak Shekarchi

  3. Department of Pathology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran

    Ahmad Oryan

  4. Physical Medicine and Rehabilitation Department, School of Medicine, AJA University of Medical Science, Tehran, Iran

    Kamran Azma

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  1. Ali Moshiri
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  2. Mostafa Shahrezaee
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Correspondence to Mostafa Shahrezaee.

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Moshiri, A., Shahrezaee, M., Shekarchi, B. et al. Three-Dimensional Porous Gelapin–Simvastatin Scaffolds Promoted Bone Defect Healing in Rabbits. Calcif Tissue Int 96, 552–564 (2015). https://doi.org/10.1007/s00223-015-9981-9

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  • DOI: https://doi.org/10.1007/s00223-015-9981-9

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