Whitlockite Promotes Bone Healing in Rabbit Ilium Defect Model
- 70 Downloads
Abstract
Purpose
Treatment of bone defects commonly employs bone substitutes, like hydroxyapatite (HAP) and β-tricalcium phosphate (β-TCP) for promoting bone regeneration. However, both the phosphates have limitations with regards to biodegradability and mechanical strength; apparently, there exists a need for other novel phosphates material with an ability to promote optimal bone regeneration. Whitlockite (WH) is the second most abundant phosphate present in the human body and its superiority has only been proven in rat calvarial model. Therefore, in the present study, we have compared osteoconductivity of WH with hydroxyapatite (HAP) and β-tricalcium phosphate (β-TCP) by employing human mesenchymal stem cells and a rabbit ilium defect model.
Methods
The effects of WH on proliferation, alkaline phosphatase activity, and expression of osteogenetic related genes in human mesenchymal stem cells were analyzed. The implants made of HAP, β-TCP or WH were inserted in rabbit ilium defect, and after 6 weeks, the bone formation in each group was analyzed with micro-CT.
Results
The cells in the WH group exhibited higher proliferation level, ALP activity, and expression levels of osteoblastic related genes. In rabbit ilium defect model, the WH group had compatible percent bone volume compared to the other two groups. Additionally, the newly formed bone in the WH group had significantly thicker bone compared to other groups with a more directional form and migrated wider in the scaffold.
Conclusions
WH exhibited comparable osteoinductivity with HAP and β-TCP in rabbit ilium defect and is proposed as a better bone substitute material.
Keywords
Bone substitute Phosphates Whitlockite Animal experiments Bone defectNotes
Funding
The work was supported by the Interdisciplinary Research Initiatives Program by College of Engineering and College of Medicine, Seoul National University (800-20150094).
Compliance with Ethical Standards
Conflict of interest
All authors declared no conflict of interest.
References
- 1.Elsalanty, M. E., & Genecov, D. G. (2009). Bone grafts in craniofacial surgery. Craniomaxillofac Trauma Reconstr, 2(3), 125–134.CrossRefGoogle Scholar
- 2.Campana, V., Milano, G., Pagano, E., Barba, M., Cicione, C., Salonna, G., et al. (2014). Bone substitutes in orthopaedic surgery: From basic science to clinical practice. Journal of Materials Science, 25(10), 2445–2461.Google Scholar
- 3.Das, S. P., Ganesh, S., Pradhan, S., Singh, D., & Mohanty, R. N. (2014). Effectiveness of recombinant human bone morphogenetic protein-7 in the management of congenital pseudoarthrosis of the tibia: A randomised controlled trial. International Orthopaedics, 38(9), 1987–1992.CrossRefGoogle Scholar
- 4.Kadam, A., Millhouse, P. W., Kepler, C. K., Radcliff, K. E., Fehlings, M. G., Janssen, M. E., et al. (2016). Bone substitutes and expanders in spine surgery: A review of their fusion efficacies. International Journal of Spine Surgery, 10, 33.CrossRefGoogle Scholar
- 5.Hsu, C. J., Chou, W. Y., Teng, H. P., Chang, W. N., & Chou, Y. J. (2005). Coralline hydroxyapatite and laminectomy-derived bone as adjuvant graft material for lumbar posterolateral fusion. Journal of Neurosurgery: Spine, 3(4), 271–275.Google Scholar
- 6.Dai, L. Y., & Jiang, L. S. (2008). Single-level instrumented posterolateral fusion of lumbar spine with beta-tricalcium phosphate versus autograft: A prospective, randomized study with 3-year follow-up. Spine (Phila Pa 1976), 33(12), 1299–1304.CrossRefGoogle Scholar
- 7.Kong, S., Park, J. H., & Roh, S. W. (2013). A prospective comparative study of radiological outcomes after instrumented posterolateral fusion mass using autologous local bone or a mixture of beta-tcp and autologous local bone in the same patient. Acta Neurochirurgica (Wien), 155(5), 765–770.CrossRefGoogle Scholar
- 8.Thaler, M., Lechner, R., Gstottner, M., Kobel, C., & Bach, C. (2013). The use of beta-tricalcium phosphate and bone marrow aspirate as a bone graft substitute in posterior lumbar interbody fusion. European Spine Journal, 22(5), 1173–1182.CrossRefGoogle Scholar
- 9.Venkatesan, J., & Kim, S. K. (2014). Nano-hydroxyapatite composite biomaterials for bone tissue engineering: A review. Journal of Biomedical Nanotechnology, 10(10), 3124–3140.CrossRefGoogle Scholar
- 10.Henry, M. G., Cai, L., Liu, X., Zhang, L., Dong, J., Chen, L., et al. (2015). Roles of hydroxyapatite allocation and microgroove dimension in promoting preosteoblastic cell functions on photocured polymer nanocomposites through nuclear distribution and alignment. Langmuir, 31(9), 2851–2860.CrossRefGoogle Scholar
- 11.Teng, Y., Giambini, H., Rezaei, A., Liu, X., Lee Miller, I. A., Waletzki, B. E., et al. (2018). Poly(propylene fumarate)-hydroxyapatite nanocomposite can be a suitable candidate for cervical cages. Journal of Biomechanical Engineering, 140(10), 101008–101009.CrossRefGoogle Scholar
- 12.Lee, D. W., Lee, J. W., Kim, S. B., Park, J. H., Chung, K. S., Ha, J. K., et al. (2017). Comparison of poly-l-lactic acid and poly-l-lactic acid/hydroxyapatite bioabsorbable screws for tibial fixation in ACL reconstruction: clinical and magnetic resonance imaging results. Clinics in Orthopedic Surgery, 9(3), 270–279.CrossRefGoogle Scholar
- 13.Sakamoto, A., Okamoto, T., & Matsuda, S. (2018). Unsintered hydroxyapatite and poly-l-lactide composite screws/plates for stabilizing beta-tricalcium phosphate bone implants. Clinics in Orthopedic Surgery, 10(2), 253–259.CrossRefGoogle Scholar
- 14.Nabiyouni, M., Brückner, T., Zhou, H., Gbureck, U., & Bhaduri, S. B. (2018). Magnesium-based bioceramics in orthopedic applications. Acta Biomaterialia, 66, 23–43.CrossRefGoogle Scholar
- 15.Rude, R. K., Singer, F. R., & Gruber, H. E. (2009). Skeletal and hormonal effects of magnesium deficiency. Journal of the American College of Nutrition, 28(2), 131–141.CrossRefGoogle Scholar
- 16.Diba, M., Tapia, F., Boccaccini, A. R., & Strobel, L. A. (2012). Magnesium-containing bioactive glasses for biomedical applications. International Journal of Applied Glass Science, 3(3), 221–253.CrossRefGoogle Scholar
- 17.Staiger, M. P., Pietak, A. M., Huadmai, J., & Dias, G. (2006). Magnesium and its alloys as orthopedic biomaterials: A review. Biomaterials, 27(9), 1728–1734.CrossRefGoogle Scholar
- 18.Meinke, D., Skinner, H., & Thomson, K. (1979). X-ray diffraction of the calcified tissues in polypterus. Calcified Tissue International, 28(1), 37–42.CrossRefGoogle Scholar
- 19.Jang, H. L., Jin, K., Lee, J., Kim, Y., Nahm, S. H., Hong, K. S., et al. (2014). Revisiting whitlockite, the second most abundant biomineral in bone: nanocrystal synthesis in physiologically relevant conditions and biocompatibility evaluation. ACS Nano, 8(1), 634–641.CrossRefGoogle Scholar
- 20.Jang, H. L., Zheng, G. B., Park, J., Kim, H. D., Baek, H. R., Lee, H. K., et al. (2016). In vitro and in vivo evaluation of whitlockite biocompatibility: Comparative study with hydroxyapatite and beta-tricalcium phosphate. Advanced Healthcare Materials, 5(1), 128–136.CrossRefGoogle Scholar
- 21.Zhou, D., Qi, C., Chen, Y. X., Zhu, Y. J., Sun, T. W., Chen, F., et al. (2017). Comparative study of porous hydroxyapatite/chitosan and whitlockite/chitosan scaffolds for bone regeneration in calvarial defects. International Journal of Nanomedicine, 12, 2673–2687.CrossRefGoogle Scholar
- 22.Kim, H. D., Jang, H. L., Ahn, H. Y., Lee, H. K., Park, J., Lee, E. S., et al. (2017). Biomimetic whitlockite inorganic nanoparticles-mediated in situ remodeling and rapid bone regeneration. Biomaterials, 112, 31–43.CrossRefGoogle Scholar
- 23.Pearce, A. I., Richards, R. G., Milz, S., Schneider, E., & Pearce, S. G. (2007). Animal models for implant biomaterial research in bone: A review. European Cells & Materials Journal, 13, 1–10.CrossRefGoogle Scholar
- 24.Samavedi, S., Whittington, A. R., & Goldstein, A. S. (2013). Calcium phosphate ceramics in bone tissue engineering: A review of properties and their influence on cell behavior. Acta Biomaterialia, 9(9), 8037–8045.CrossRefGoogle Scholar
- 25.Lakhkar, N. J., Lee, I. H., Kim, H. W., Salih, V., Wall, I. B., & Knowles, J. C. (2013). Bone formation controlled by biologically relevant inorganic ions: Role and controlled delivery from phosphate-based glasses. Advanced Drug Delivery Reviews, 65(4), 405–420.CrossRefGoogle Scholar
- 26.Lu, W. C., Pringa, E., & Chou, L. (2017). Effect of magnesium on the osteogenesis of normal human osteoblasts. Magnesium Research, 30(2), 42–52.Google Scholar
- 27.McGovern, J. A., Griffin, M., & Hutmacher, D. W. (2018). Animal models for bone tissue engineering and modelling disease. Disease Models & Mechanisms, 11(4), dmm033084.CrossRefGoogle Scholar
- 28.Gomes, P. S., & Fernandes, M. H. (2011). Rodent models in bone-related research: The relevance of calvarial defects in the assessment of bone regeneration strategies. Laboratory Animals, 45(1), 14–24.MathSciNetCrossRefGoogle Scholar
- 29.Anderson, M. L., Dhert, W. J., de Bruijn, J. D., Dalmeijer, R. A., Leenders, H., van Blitterswijk, C. A., et al. (1999). Critical size defect in the goat’s os ilium: A model to evaluate bone grafts and substitutes. Clinical Orthopaedics and Related Research, 364, 231–239.CrossRefGoogle Scholar
- 30.Li, Y., Chen, S.-K., Li, L., Qin, L., Wang, X.-L., & Lai, Y.-X. (2015). Bone defect animal models for testing efficacy of bone substitute biomaterials. Journal of Orthopaedic Translation, 3(3), 95–104.CrossRefGoogle Scholar