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Cited 3 time in webofscience Cited 4 time in scopus
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Cell spheroids containing bioactive molecule-immobilized porous particles with a leaf-stacked structure

Authors
Kim, Min JiJeoung, Yeoung JoKim, Ho YongKim, So YoungKim, Jeong YunPark, Jae WonByun, June-HoLee, Jin HoOh, Se Heang
Issue Date
1-Feb-2022
Publisher
ELSEVIER SCIENCE SA
Keywords
Cell spheroid; Leaf-stacked structure; Microparticles; Bone morphogenetic protein-2 (BMP-2); Bone marrow-derived mesenchymal stem cells; (BMSCs); Delivery system
Citation
CHEMICAL ENGINEERING JOURNAL, v.429
Indexed
SCIE
SCOPUS
Journal Title
CHEMICAL ENGINEERING JOURNAL
Volume
429
URI
https://scholarworks.bwise.kr/gnu/handle/sw.gnu/1635
DOI
10.1016/j.cej.2021.132590
ISSN
1385-8947
Abstract
Despite the widespread use of cell spheroids in tissue engineering for the regeneration of large tissues and organs and for high-throughput screening in pharmacology and toxicology, the clinical challenges include cellular heterogeneity, low structural stability, and uncontrolled cell differentiation. Using human bone marrow-derived mesenchymal stem cells (hBMSCs), we developed cell spheroids containing bioactive molecule (bone morphogenetic protein-2, BMP-2)-immobilized polycaprolactone (PCL) particles with a leaf-stacked structure (LSS). The LSS particles were fabricated via simple heating-cooling method, and the BMP-2 was continuously released from LSS particles for 19 days. Based on in vitro and in vivo observations of the cell spheroids, we found that (i) the porous LSS particles prevent cellular heterogeneity via sufficient diffusion of oxygen/nutrients, (ii) the cell adhesive surface on LSS particles improved the structural stability, (iii) the BMP-2 released from LSS particles induced effective osteogenic differentiation of stem cells, and (iv) the BMP-2-immobilized LSS particles induced new bone formation. Therefore, the cell spheroid containing bioactive molecule-immobilized LSS particles represent a potential strategy to overcome the inherent limitations of conventional cell spheroids. We further suggest that the cell spheroid containing bioactive molecule-immobilized LSS particles is an elegant platform for the regeneration of various tissues and organs as well as high-throughput screening in pharmacology and toxicology studies.
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