title: Biomimetic whitlockite inorganic nanoparticles-mediated in situ remodeling and rapid bone regeneration.
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 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 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.
authors.affiliation: School of Chemical and Biological Engineering, NBio Institute, Institute of Chemical Processes, Seoul National University, Seoul, 151-744, Republic of Korea.
authors.forename: Hwan D
authors.initials: HD
authors.lastname: Kim
authors.affiliation: Department of Materials Science and Engineering, Seoul National University, Seoul, 151-744, Republic of Korea.
authors.forename: Hae Lin
authors.initials: HL
authors.lastname: Jang
authors.affiliation: Department of Materials Science and Engineering, Seoul National University, Seoul, 151-744, Republic of Korea.
authors.forename: Hyo-Yong
authors.initials: HY
authors.lastname: Ahn
authors.affiliation: Department of Materials Science and Engineering, Seoul National University, Seoul, 151-744, Republic of Korea.
authors.forename: Hye Kyoung
authors.initials: HK
authors.lastname: Lee
authors.affiliation: School of Chemical and Biological Engineering, NBio Institute, Institute of Chemical Processes, Seoul National University, Seoul, 151-744, Republic of Korea.
authors.forename: Jungha
authors.initials: J
authors.lastname: Park
authors.affiliation: School of Chemical and Biological Engineering, NBio Institute, Institute of Chemical Processes, Seoul National University, Seoul, 151-744, Republic of Korea.
authors.forename: Eun-Seo
authors.initials: ES
authors.lastname: Lee
authors.affiliation: School of Chemical and Biological Engineering, NBio Institute, Institute of Chemical Processes, Seoul National University, Seoul, 151-744, Republic of Korea.
authors.forename: Eunjee A
authors.initials: EA
authors.lastname: Lee
authors.affiliation: Division of Orthodontics, College of Dentistry, The Ohio State University, Columbus, OH 43120, USA.
authors.forename: Yong-Hoon
authors.initials: YH
authors.lastname: Jeong
authors.affiliation: Division of Orthodontics, College of Dentistry, The Ohio State University, Columbus, OH 43120, USA.
authors.forename: Do-Gyoon
authors.initials: DG
authors.lastname: Kim
authors.affiliation: Department of Materials Science and Engineering, Seoul National University, Seoul, 151-744, Republic of Korea. Electronic address: nkitae@snu.ac.kr.
authors.forename: Ki Tae
authors.initials: KT
authors.lastname: Nam
authors.affiliation: School of Chemical and Biological Engineering, NBio Institute, Institute of Chemical Processes, Seoul National University, Seoul, 151-744, Republic of Korea. Electronic address: nshwang@snu.ac.kr.
authors.forename: Nathaniel S
authors.initials: NS
authors.lastname: Hwang
mesh_terms: D040761:Biomimetic Materials / Q000008:administration & dosage* / Q000138:chemical synthesis; D001861:Bone Regeneration / Q000187:drug effects* / Q000502:physiology*; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology; D002113:Calcification, Physiologic / Q000187:drug effects / Q000502:physiology; D002130:Calcium Phosphates / Q000008:administration & dosage* / Q000737:chemistry*; D002478:Cells, Cultured; D006801:Humans; D008422:Materials Testing; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size
chemical_list: D002130:Calcium Phosphates; C021767:whitlockite
keywords: Bone remodeling process; Bone tissue engineering; Cryogel; Inorganic phosphate; Ion metabolic pathway; Nanoparticles; Whitlockite