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      Effect of ErhBMP-2-loaded β-tricalcium phosphate on ulna defects in the osteoporosis rabbit model

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          Abstract

          Purpose

          Autografts, the gold standard treatment for large bone defects, present complications, especially in conditions with reduced bone-repair capacity, such as osteoporosis. Escherichia coli-derived recombinant human bone morphogenesis protein-2 (ErhBMP-2), was used in this study to improve the osteoinductivity of β-tricalcium phosphate (β-TCP). This study evaluated the bone-repair capacity of ErhBMP-2-loaded β-TCP on osteoporosis rabbit model, relative to the sole use of autograft and β-TCP treatments.

          Methods

          The osteoporosis rabbit model was induced through ovariectomy and glucocorticoid dosing; 2-cm segmental ulnar defects were created, which were treated with either autograft, β-TCP alone, or ErhBMP-2-loaded β-TCP or left untreated. The quality of newly formed ulnae was evaluated 8 weeks after ulnar surgery through micro-CT, biomechanical, histological, and histomorphometric assessments.

          Results

          The osteoporosis rabbit model was developed and maintained till the end of the study. The maximal load and stiffness in the ErhBMP-2-loaded TCP group were significantly higher than those in the autograft group, whereas the TCP-alone group performed similarly as did the untreated group in the force loading and stiffness tests. According to the micro-CT evaluation, the ErhBMP-2-loaded TCP group had significantly higher bone volume relative to the autograft and TCP-alone groups. Histological assessments revealed better defect bridging and marrow formation in the ErhBMP-2-loaded TCP group relative to the TCP-alone group. Mineral apposition rates were significantly higher in the ErhBMP-2-loaded TCP and autograft groups than in the TCP-alone and untreated groups.

          Conclusion

          Relative to autografts, ErhBMP-2-loaded TCP, as an alternative grafting material, provides better or comparable healing on critical-sized long bone defects in the osteoporosis rabbit model.

          Graphical abstract

          Highlights

          • •

            Erh-BMP-2 promoted the bone healing ability of β-TCP in osteoporosis animal model.

          • •

            New bone generated by Erh-BMP-2-loaded β-TCP was stiffer than that generated by autograft.

          • •

            ErhBMP-2-loaded TCP potentially being an alternative grafting material relative to autograft.

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          Most cited references26

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          Standardized nomenclature, symbols, and units for bone histomorphometry: a 2012 update of the report of the ASBMR Histomorphometry Nomenclature Committee.

          David W. Dempster, Juliet Compston, Marc Drezner … (2013)
          Article 0 comments Cited 407 times – based on 0 reviews     Review now
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            Delayed union and nonunions: epidemiology, clinical issues, and financial aspects.

            David J Hak, Daniel Fitzpatrick, Julius A Bishop … (2014)
            Fracture healing is a critically important clinical event for fracture patients and for clinicians who take care of them. The clinical evaluation of fracture healing is based on both radiographic findings and clinical findings. Risk factors for delayed union and nonunion include patient dependent factors such as advanced age, medical comorbidities, smoking, non-steroidal anti-inflammatory use, various genetic disorders, metabolic disease and nutritional deficiency. Patient independent factors include fracture pattern, location, and displacement, severity of soft tissue injury, degree of bone loss, quality of surgical treatment and presence of infection. Established nonunions can be characterised in terms of biologic capacity, deformity, presence or absence of infection, and host status. Hypertrophic, oligotrophic and atrophic radiographic appearances allow the clinician to make inferences about the degree of fracture stability and the biologic viability of the fracture fragments while developing a treatment plan. Non-unions are difficult to treat and have a high financial impact. Indirect costs, such as productivity losses, are the key driver for the overall costs in fracture and non-union patients. Therefore, all strategies that help to reduce healing time with faster resumption of work and activities not only improve medical outcome for the patient, they also help reduce the financial burden in fracture and non-union patients. Copyright © 2014 Elsevier Ltd. All rights reserved.
            Article 0 comments Cited 167 times – based on 0 reviews     Review now
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              The use of bone-graft substitutes in large bone defects: any specific needs?

              Bruno Colombo, G Calori, Maureen Mazza … (2011)
              The gold standard for restoring bone defects is still considered to be autologous bone grafting. However, clinical benefits are not guaranteed and donor-site complications and morbidity is not infrequent. Research is on-going for the development of alternative bone substitutes of both biological and synthetic origin. The purpose of this study was to evaluate the type of materials used and their efficacy for the treatment of large bone defects in traumatology and orthopaedic surgery. A literature review was carried out of Embase and PubMed databases. Inclusion criteria were articles in English language focusing on the use of bone substitutes in trauma and orthopaedic surgery for the treatment of bone defects and included details on the structural, biological or biomechanical properties of the pure product. Furthermore, based on two clinical challenges, fracture non-union and impaction grafting we elaborated on the use of polytherapy for large bone defects as guided by the diamond concept. All the products indicated in this manuscript possess osteoconductive activities but have different resorption times and biomechanical properties. Bone graft substitute materials are used for a wide range of clinical applications even when the level of clinical evidence is low. The size and location of the defect and the local biological and mechanical environment as well as the biomechanical characteristics of the material determine the type of device that can be implanted in a bone defect. Proper assessment of the biological and mechanical environment and accurate patient selection are necessary to judge the extent of therapy the injury warrants. A sound understanding of various aspects of biomaterial properties and their relation and influence towards bone healing is of utmost importance. We suggest the application of polytherapy for the treatment of large bone defects and advocate the use of the diamond concept as a guideline. Copyright © 2011 Elsevier Ltd. All rights reserved.
              Article 0 comments Cited 108 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Jian-Ming Chen
                Journal
                Journal ID (nlm-ta): Bone Rep
                Journal ID (iso-abbrev): Bone Rep
                Title: Bone Reports
                Publisher: Elsevier
                ISSN (Electronic): 2352-1872
                Publication date PMC-release: 10 December 2020
                Publication date Collection: June 2021
                Publication date (Electronic): 10 December 2020
                Volume: 14
                Electronic Location Identifier: 100739
                Affiliations
                [a ]Ph.D. Program for Biotech Pharmaceutical Industry, School of Pharmacy, China Medical University, Taichung 40402, Taiwan
                [b ]Department of Orthopedics, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 10002, Taiwan
                [c ]Department of Biomedical Engineering, Yuanpei University of Medical Technology, Hsinchu 30015, Taiwan
                [d ]Department of Orthopedics, En Chu Kong Hospital, New Taipei City 23702, Taiwan
                [e ]Department of Orthopaedics, School of Medicine, College of Medicine, Taipei Medical University, Taiwan
                [f ]Department of Orthopaedics, Shuang Ho Hospital, Taipei Medical University, Taiwan
                [g ]Department of Orthopedic Surgery, Chang Gung Memorial Hospital-Linkou, Tao-Yuan 33305, Taiwan
                [h ]Bone and Joint Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan
                Author notes
                [* ]Corresponding author at: Department of Orthopedic Surgery, Chang Gung Memorial Hospital-Linkou, Tao-Yuan 33305, Taiwan. vantchen@ 123456gmail.com
                Article
                Publisher Item ID: S2352-1872(20)30499-X Publisher ID: 100739
                DOI: 10.1016/j.bonr.2020.100739
                PMC ID: 7750155
                PubMed ID: 33364265
                SO-VID: 1cc13a34-c683-4f8c-a6bd-65a9cf54b6c9
                Copyright © © 2020 The Authors
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 29 July 2020
                Date revision received : 27 November 2020
                Date accepted : 4 December 2020
                Categories
                Subject: Article

                Keywords: bmc, bone mineral content,bmd, bone mineral density,bv, bone volume,β-tcp, β-tricalcium phosphate,erhbmp-2, escherichia coli-derived recombinant human bone morphogenesis protein-2,roi, region of interest,ulna defect,osteoporosis rabbit model,erhbmp-2,tricalcium phosphate
                Data availability:
                Keywords: bmc, bone mineral content, bmd, bone mineral density, bv, bone volume, β-tcp, β-tricalcium phosphate, erhbmp-2, escherichia coli-derived recombinant human bone morphogenesis protein-2, roi, region of interest, ulna defect, osteoporosis rabbit model, erhbmp-2, tricalcium phosphate

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