한빛사논문
Hayeon Byun1,2, Sangmin Lee1,2, Gyu Nam Jang1,2, Hyoryong Lee3, Sukho Park3 and Heungsoo Shin5,1,2,4
1Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea
2BK21 FOUR Education and Research Group for Biopharmaceutical Innovation Leader, Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, 04763, Republic of Korea
3Department of Robotics Engineering, Daegu Gyeongbuk Institute of Science and Technology, 333 Techno Jungang Daero, Hyeonpung-eup, Dalseong-gun, Daegu 42988, Republic of Korea
4Institute of Nano Science and Technology, Hanyang University, 222 Wangsimri-ro, Seongdong-gu, Seoul 04763, Republic of Korea
5Author to whom any correspondence should be addressed.
Abstract
Biofabrication of organ-like engineered 3D tissue through the assembly of magnetized 3D multi-cellular spheroids has been recently investigated in tissue engineering. However, the cytotoxicity of magnetic nanoparticles (MNPs) and contraction-induced structural deformation of the constructs have been major limitations. In this study, we developed a method to fabricate composite stem cell spheroids using MNP-coated fibers, alleviating MNP-mediated toxicity and controlling structural assembly under external magnetic stimuli. The MNP-coated synthetic fibers (MSFs) were prepared by coating various amounts of MNPs on the fibers via electrostatic interactions. The MSFs showed magnetic hysteresis and no cytotoxicity on 2D-cultured adipose-derived stem cells (ADSCs). The composite spheroids containing MSFs and ADSCs were rapidly formed in which the amount of impregnated MSFs modulated the spheroid size. The fusion of in vitro composite spheroids was then monitored at the contacting interface; the fused spheroids with over 10 μg of MSF showed minimal contraction after 7 d, retaining around 90% of total area ratio regardless of the number of cells, indicating that the presence of fibers within the composite spheroid supported its structural maintenance. The fusion of MSF spheroids was modulated by external magnetic stimulation, and the effect of magnetic force on the movement and fusion of the spheroids was investigated using COMSOL simulation. Finally, ring and lamellar structures were successfully assembled using remote-controlled MSF spheroids, showing limited deformation and high viability up to 50 d during in vitro culture. In addition, the MSFs demonstrated no adverse effects on ADSC osteochondral differentiation. Altogether, we envision that our magnetic assembly system would be a promising method for the tissue engineering of structurally controlled organ-like constructs.
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