한빛사논문
서울대학교
Jinkyu Lee, Seoyun Lee, Seung Jae Huh, Byung-Jae Kang, and Heungsoo Shin*
J. Lee, S. J. Huh, H. Shin
Department of Bioengineering Institute for Bioengineering and Biopharmaceutical Research Hanyang University 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea
J. Lee
BK21 FOUR Human-Tech Convergence Program Hanyang University 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea
S. Lee, B.-J. Kang
Department of Veterinary Clinical Sciences College of Veterinary Medicine and Research Institute for Veterinary Science BK21 FOUR Future Veterinary Medicine Leading Education and Research Center Seoul National University 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea
S. J. Huh, H. Shin
BK21 FOUR Education and Research Group for Biopharmaceutical Innovation Leader Hanyang University 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea
H. Shin
Institute of Nano Science and Technology Hanyang University 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea
J.L. and S.L. contributed equally to this work.
*Corresponding author.
Abstract
The use of engineered scaffolds or stem cells is investigated widely in the repair of injured musculoskeletal tissue. However, the combined regeneration of hierarchical osteochondral tissue remains a challenge due to delamination between cartilage and subchondral bone or difficulty in spatial control over differentiation of transplanted stem cells. Here, two types of composite spheroids are prepared using adipose-derived stem cells (hADSCs) and nanofibers coated with either transforming growth factor-β3 or bone morphogenetic growth factor-2 for chondrogenesis or osteogenesis, respectively. Each type of spheroid is then cultured within a 3D-printed microchamber in a spatially arranged manner to recapitulate the bilayer structure of osteochondral tissue. The presence of inductive factors regionally modulates in vitro chondrogenic or osteogenic differentiation of hADSCs within the biphasic construct without dedifferentiation. Furthermore, hADSCs from each spheroid proliferate and sprout and successfully connect the two layers mimicking the osteochondral interface without apertures. In vivo transplantation of the biphasic construct onto a femoral trochlear groove defect in rabbit knee joint results in 21.2 ± 2.8% subchondral bone volume/total volume and a cartilage score of 25.0 ± 3.7. The present approach can be an effective therapeutic platform to engineer complex tissue.
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