title: Magnetic nanocomposite scaffolds combined with static magnetic field in the stimulation of osteoblastic differentiation and bone formation.
abstract: Magnetism has recently been implicated to play significant roles in the regulation of cell responses. Allowing cells to experience a magnetic field applied externally or scaffolding them in a material with intrinsic magnetic properties has been a possible way of utilizing magnetism. Here we aim to investigate the combined effects of the external static magnetic field (SMF) with magnetic nanocomposite scaffold made of polycaprolactone/magnetic nanoparticles on the osteoblastic functions and bone formation. The SMF synergized with the magnetic scaffolds in the osteoblastic differentiation of primary mouse calvarium osteoblasts, including the expression of bone-associated genes (Runx2 and Osterix) and alkaline phosphatase activity. The synergism was demonstrated in the activation of integrin signaling pathways, such as focal adhesion kinase, paxillin, RhoA, mitogen-activated protein kinase, and nuclear factor-kappaB, as well as in the up-regulation of bone morphogenetic protein-2 and phosphorylation of Smad1/5/8. Furthermore, the SMF/magnetic scaffold-stimulated osteoblasts promoted the angiogenic responses of endothelial cells, including the expression of vascular endothelial growth factor and angiogenin-1 genes and the formation of capillary tubes. When the magnetic scaffolds were implanted in mouse calvarium defects, the application of SMF significantly enhanced the new bone formation at 6 weeks, as revealed by the histological and micro-computed tomographic analyses. Current findings suggest that the combinatory application of external (SMF) and internal (scaffold) magnetism can be a promising tool to regenerative engineering of bone.
authors: Department of Oral and Maxillofacial Pathology, and Research Center for Tooth and Periodontal Regeneration (MRC), School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
authors: Hyung-Mun
authors: HM
authors: Yun
authors: Department of Prosthodontics, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
authors: Su-Jin
authors: SJ
authors: Ahn
authors: Department of Oral and Maxillofacial Pathology, and Research Center for Tooth and Periodontal Regeneration (MRC), School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
authors: Kyung-Ran
authors: KR
authors: Park
authors: Department of Oral and Maxillofacial Pathology, and Research Center for Tooth and Periodontal Regeneration (MRC), School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
authors: Mi-Joo
authors: MJ
authors: Kim
authors: Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, Republic of Korea; Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, Republic of Korea.
authors: Jung-Ju
authors: JJ
authors: Kim
authors: Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, Republic of Korea; Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, Republic of Korea.
authors: Guang-Zhen
authors: GZ
authors: Jin
authors: Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, Republic of Korea; Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, Republic of Korea; Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan, Republic of Korea. Electronic address: kimhw@dku.edu.
authors: Hae-Won
authors: HW
authors: Kim
authors: Department of Oral and Maxillofacial Pathology, and Research Center for Tooth and Periodontal Regeneration (MRC), School of Dentistry, Kyung Hee University, Seoul, Republic of Korea. Electronic address: eckim@khu.ac.kr.
authors: Eun-Cheol
authors: EC
authors: Kim
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism; D016023:Integrins / Q000235:genetics / Q000378:metabolism; D060526:Magnetic Fields; D051379:Mice; D008813:Mice, Inbred ICR; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D053761:Nanocomposites / Q000737:chemistry*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects*; D051419:Paxillin / Q000235:genetics / Q000378:metabolism; D011091:Polyesters / Q000737:chemistry; D012259:Ribonuclease, Pancreatic / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry*; D015854:Up-Regulation; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020742:rhoA GTP-Binding Protein
chemical_list: D016023:Integrins; D016328:NF-kappa B; D051419:Paxillin; D011091:Polyesters; C496062:Pxn protein, mouse; C016240:polycaprolactone; D051417:Focal Adhesion Kinase 1; C496051:Ptk2 protein, mouse; D020928:Mitogen-Activated Protein Kinases; C046366:angiogenin; D012259:Ribonuclease, Pancreatic; C526380:RhoA protein, mouse; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein
keywords: Angiogenesis; Bone regeneration; Magnetic scaffolds; Osteoblastic differentiation; Static magnetic field