한빛사논문
Tiep Tien Nguyena,b, Mai Thi Phuongb, Manju Shresthac, Junhyeung Parkc, Pham Le Minhb, Jong Oh Kimb, Hyukjae Choib, Joo-Won Namb, Hu-Lin Jiangd,e,f,g, Hyung-Sik Kimh,i, Jee-Heon Jeongc,*, Jun-Beom Parkj,*, Simmyung Yooka,*
aCollege of Pharmacy, Keimyung University, Daegu, 42601, Republic of Korea
bCollege of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk 38541, Republic of Korea
cDepartment of Precision Medicine, School of Medicine, Sungkyunkwan University, Suwon 16419, Republic of Korea
dState Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
eJiangsu Key Laboratory of Druggability of Biopharmaceuticals, China Pharmaceutical University, Nanjing, 210009, China.
fJiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing, 210009, China.
gNMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, China Pharmaceutical University, Nanjing, 210009, China.
hDepartment of Life Science in Dentistry, School of Dentistry, Pusan National University, Yangsan, 50612, Republic of Korea
iDental and Life Science Institute, Pusan National University, Yangsan, 50612, Republic of Korea
jDepartment of Periodontics, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
Corresponding Authors : Jee-Heon Jeong, Jun-Beom Park, Simmyung Yook
Abstract
Potentiation of stem cell potency is critical for successful tissue engineering, especially for bone regeneration. Three-dimensional cell culture and bioactive molecule co-delivery with cells have been proposed to achieve this effect. Here, we provide a uniform and scalable fabrication of osteogenic microtissue constructs of mesenchymal stem cell (MSC) spheroids surface-engineered with dexamethasone-releasing polydopamine-coated microparticles (PD-DEXA/MPs) to target bone regeneration. The microparticle conjugation process was rapid and cell-friendly and did not affect the cell viability or key functionalities. The incorporation of DEXA in the conjugated system significantly enhanced the osteogenic differentiation of MSC spheroids, as evidenced by upregulating osteogenic gene expression and intense alkaline phosphatase and alizarin red S staining. In addition, the migration of MSCs from spheroids was tested on a biocompatible macroporous fibrin scaffold (MFS). The result showed that PD-DEXA/MPs were stably anchored on MSCs during cell migration over time. Finally, the implantation of PD-DEXA/MP-conjugated spheroid-loaded MFS into a calvarial defect in a mouse model showed substantial bone regeneration. In conclusion, the uniform fabrication of microtissue constructs containing MSC spheroids with drug depots shows a potential to improve the performance of MSCs in tissue engineering.
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