한빛사논문
- 조회1,162
Min Ji Kima,1, Yeoung Jo Jeoungb,1, Ho Yong Kima, So Young Kima, Jeong Yun Kimc, Jae Won Parkd, June-Ho Byune, Jin Ho Leeb,*, Se Heang Oha,*
aDepartment of Nanobiomedical Science, Dankook University, Cheonan 31116, Republic of Korea
bDepartment of Advanced Materials, Hannam University, Daejeon 34054, Republic of Korea
cDepartment of Physics, College of Science, Dankook University, Cheonan 31116, Republic of Korea
dSchool of Microelectronics, Southern University of Science and Technology, Shenzhen 518055, China
eDepartment of Oral and Maxillofacial Surgery, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, Institute of Health Sciences, Gyeongsang National University, Jinju, 52727, Republic of Korea
1These authors contributed equally to this work.
*Corresponding authors.
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.
Keywords : Cell spheroid, Leaf-stacked structure, Microparticles, Bone morphogenetic protein-2 (BMP-2), Bone marrow-derived mesenchymal stem cells (BMSCs), Delivery system
논문정보
- Research article
- 2021년 09월 (BRIC 등록일 2021-11-05)
- 국내(교신)+국외 연구진
- 바이오·의료융합 > 바이오소재
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