4.8 Article

Biomimetic whitlockite inorganic nanoparticles-mediated in situ remodeling and rapid bone regeneration

Journal

BIOMATERIALS
Volume 112, Issue -, Pages 31-43

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2016.10.009

Keywords

Whitlockite; Nanoparticles; Inorganic phosphate; Cryogel; Bone tissue engineering; Ion metabolic pathway; Bone remodeling process

Funding

  1. Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT Future [2011-0011225]
  2. Global Frontier R&D Program on Center for Multiscale Energy System - National Research Foundation under the Ministry of Science, ICT Future, Korea [0420-20130104]
  3. Pioneer Research Center Program through the National Research Foundation of Korea - Ministry of Science, ICT & Future Planning [NRF-2011-0021021]
  4. International Research & Development Program of the National Research Foundation of Korea (NRF) - Ministry of Science, ICT & Future Planning [2013K1A3A1A32035536]
  5. National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [NRF-2012M3A9C6050102, NRF-2015K2A1B8047359]
  6. Ministry of Health and Welfare of Korea [HI13C1789]
  7. Global Ph.D. Fellowship Program from the National Research Foundation of Korea (NRF) - Ministry of Education [NRF-2015H1A2A1029321]
  8. National Research Foundation of Korea [2015H1A2A1029321, 2013K1A3A1A32035536] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

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Bone remodeling process relies on complex signaling pathway between osteoclasts and osteoclasts and control mechanisms to achieve homeostasis of their growth and differentiation. Despite previous achievements in understanding complicated signaling pathways between cells and bone extracellular matrices during bone remodeling process, a role of local ionic concentration remains to be elucidated. Here, we demonstrate that synthetic whitlockite (WH: Ca18Mg2(HPO4)(2)(PO4)(12)) nanoparticles can recapitulate early-stage of bone regeneration through stimulating osteogenic differentiation, prohibiting osteoclastic activity, and transforming into mechanically enhanced hydroxyapatite (HAP)-neo bone tissues by continuous supply of PO43- and Mg2+ under physiological conditions. In addition, based on their structural analysis, the dynamic phase transformation from WH into HAP contributed as a key factor for rapid bone regeneration with denser hierarchical neo-bone structure. Our findings suggest a ground-breaking concept of 'living bone minerals' that actively communicate with the surrounding system to induce self-healing, while previous notions about bone minerals have been limited to passive products of cellular mineralization. (C) 2016 Elsevier Ltd. All rights reserved.

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