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서울대학교

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Biomaterials, Jan 2017, 112 S0142-9612(16)30551-8 | https://doi.org/10.1016/j.biomaterials.2016.10.009 Biomimetic whitlockite inorganic nanoparticles-mediated in situ remodeling and rapid bone regeneration

Hwan D. Kim^{1 †}, Hae Lin Jang ^{2 †}, Hyo-Yong Ahn ², Hye Kyoung Lee ², Jungha Park ¹, Eun-Seo Lee ¹, Eunjee A. Lee ¹, Yong-Hoon Jeong ³, Do-Gyoon Kim ³, Ki Tae Nam ^2,*, Nathaniel S. Hwang ^1,*

¹School of Chemical and Biological Engineering, NBio Institute, Institute of Chemical Processes, Seoul National University, Seoul, 151-744, Republic of Korea.
²Department of Materials Science and Engineering, Seoul National University, Seoul, 151-744, Republic of Korea.
³Division of Orthodontics, College of Dentistry, The Ohio State University, Columbus, OH 43120, USA.

^†These authors contributed equally
^*Corresponding authors: correspondence to Ki Tae Nam or Nathaniel S. Hwang

Abstract

Bone remodeling process relies on complex signaling pathway between osteoblasts 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 PO₄^3- 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 groundbreaking 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.

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