Cell spheroids containing bioactive molecule-immobilized porous particles with a leaf-stacked structure
- Kim, Min Ji; Jeoung, Yeoung Jo; Kim, Ho Yong; Kim, So Young; Kim, Jeong Yun; Park, Jae Won; Byun, June-Ho; Lee, Jin Ho; Oh, Se Heang
- Issue Date
- ELSEVIER SCIENCE SA
- Cell spheroid; Leaf-stacked structure; Microparticles; Bone morphogenetic protein-2 (BMP-2); Bone marrow-derived mesenchymal stem cells; (BMSCs); Delivery system
- CHEMICAL ENGINEERING JOURNAL, v.429
- Journal Title
- CHEMICAL ENGINEERING JOURNAL
- 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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- College of Medicine > Department of Medicine > Journal Articles
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