한빛사 논문
Han-Sem Kima,b,1, Jung-Hwan Leea,b,c,d,e,1, Nandin Mandakhbayara,b,1, Guang-Zhen Jina,b,d, Sung-Jin Kima,b, Ji-Young Yoona,b, Seung Bin Joa,b, Jeong-Hui Parka,b, Rajendra K. Singha,b,e, Jun-Hyeog Jangf, Ueon Sang Shina,b, Jonathan C. Knowlesb,e,g,h, Hae-Won Kima,b,c,d,e.*
aInstitute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 31116, South Korea
bDepartment of Nanobiomedical Science & BK21 NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 31116, South Korea
cDepartment of Biomaterials Science, College of Dentistry, Dankook University, Cheonan 31116, South Korea
dCell & Matter Institute, Dankook University, Cheonan 31116, Republic of Korea
eUCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, Cheonan 31116, South Korea
fDepartment of Biochemistry, College of Medicine, Inha University, Incheon, Republic of Korea
gUCL Eastman Dental Institute, University College London, 256 Gray’s Inn Road, London WC1X 8LD, UK
hThe Discoveries Centre for Regenerative and Precision Medicine, UCL Campus, London, UK
1These authors contributed equally to this work.
*Corresponding author
Abstract
Natural inorganic/organic nanohybrids are a fascinating model in biomaterials design due to their ultra-microstructure and extraordinary properties. Here, we report unique-structured nanohybrids through self-assembly of biomedical inorganic/organic nanounits, composed of bioactive inorganic nanoparticle core (hydroxyapatite, bioactive glass, or mesoporous silica) and chitosan shell - namely Chit@IOC. The inorganic core thin-shelled with chitosan could constitute as high as 90%, strikingly contrasted with the conventional composites. The Chit@IOC nanohybrids were highly resilient under cyclic load and resisted external stress almost an order of magnitude effectively than the conventional composites. The nanohybrids, with the nano-roughened surface topography, could accelerate the cellular responses through stimulated integrin-mediated focal adhesions. The nanohybrids were also able to load multiple therapeutic molecules in the core and shell compartment and then release sequentially, demonstrating controlled delivery systems. The nanohybrids compartmentally-loaded with therapeutic molecules (dexamethasone, fibroblast growth factor 2, and phenamil) were shown to stimulate the anti-inflammatory, pro-angiogenic and osteogenic events of relevant cells. When implanted in the in vivo calvarium defect model with 3D-printed scaffold forms, the therapeutic nanohybrids were proven to accelerate new bone formation. Overall, the nanohybrids self-assembled from Chit@IOC nanounits, with their unique properties (ultrahigh inorganic content, nano-topography, high resilience, multiple-therapeutics delivery, and cellular activation), can be considered as promising 3D tissue regenerative platforms.
Keywords : Self-assembly, inorganic-organic nanohybrids, core-shell, ultrahigh inorganic content, resilience, controlled drug delivery, tissue regeneration
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