Effectiveness of tissue engineered three‐dimensional bioactive graft on bone healing and regeneration: an in vivo study with significant clinical value |
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Authors: | Mostafa Shahrezaie Ali Moshiri Babak Shekarchi Ahmad Oryan Nicola Maffulli Javad Parvizi |
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Affiliation: | 1. Department of Orthopedic Surgery, Faculty of Medicine, AJA University of Medical Science, Tehran, Iran;2. Department of Surgery and Radiology, Dr. Moshiri Veterinary Clinic, Tehran, Iran;3. Department of Radiology, Faculty of Medicine, AJA University of Medical Science, Tehran, Iran;4. Department of Pathology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran;5. Department of Musculoskeletal Disorders, School of Medicine and Surgery, University of Salerno, Salerno, Italy;6. Centre for Sports and Exercise Medicine, Queen Mary University of London, Barts and the London School of Medicine and Dentistry, Mile End Hospital, London, UK;7. Department of Orthopaedics, The Rothman Institute at Thomas Jefferson University Hospital, Philadelphia, PA, USA |
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Abstract: | Several strategies have been used to promote bone repair, with many failing due to the lack of osteoinduction. This report describes an approach for promoting bone healing that attempts to overcome prior shortcomings. First, the role was compared of different concentrations of gelatine (Gel), nanostructured‐hydroxyapatite (nHA), simvastatin (Sim) and nHA‐Sim particles on healing of small femoral bone defects in rabbits. The effective concentration of each was studied, and then a three‐dimensional porous scaffold was designed using Gel, nHA and Sim, which was then cross‐linked with genipin. Morphology, degradation profile and Sim delivery properties of the scaffolds were evaluated in vitro. Then, the scaffolds were subcutaneously tested in vivo to determine their biocompatibility, biodegradability and osteogenic properties. Finally, the scaffolds were implanted in a large radial bone defect model in rabbits and their effect on bone regeneration was investigated. The Gel, nHA and Sim with concentrations of 1, 1 and 5 mg/femoral hole were effective during bone healing respectively, and the Sim showed the most osteoinduction and osteoconduction when compared to controls. The Gel‐Sim and Gel‐nHA‐Sim scaffolds continuously and homogenously released Sim into the simulated body fluid in vitro. Subcutaneously, the scaffolds were biocompatible, biodegradable and able to produce ectopic bone after 30 days. Thirty and 60 days after implantation of the scaffolds in radial bone defects, they were completely degraded and replaced with the new bone that had significantly superior morphology, mineral density, bioelectrical, biophysical and micromechanical properties compared with controls. Such bioactive grafts may be a suitable option for bone reconstruction, healing and repair. |
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Keywords: | gelatine genipin healing and regeneration nanohydroxyapatite simvastatin tissue engineering |
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