한빛사 논문
Seong Jin Lee6,1, Yoojun Nam6,2,3, Yeri Alice Rim2,3, Kijun Lee2, Ji Hyeon Ju7,2,3 and Dong Sung Kim7,1,4,5
1Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), 77, Cheongam-ro, Nam-gu, Pohang, Gyeongbuk 37673, Republic of Korea
2Catholic iPSC Research Center, College of Medicine, The Catholic University of Korea, 20 Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea
3Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, Institute of Medical Science, College of Medicine, The Catholic University of Korea, 20 Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea
4Department of Chemical Engineering, Pohang University of Science and Technology (POSTECH), 77, Cheongam-ro, Nam-gu, Pohang, Gyeongbuk 37673, Republic of Korea
5Institute for Convergence Research and Education in Advanced Technology, Yonsei University, 50, Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea
6These authors contributed equally to this work.
7Authors to whom any correspondence should be addressed.
Abstract
The pellet formation has been regarded as a golden standard for in vitro chondrogenic differentiation. However, a spatially inhomogeneous chondrogenic microenvironment around a pellet resulted from the use of a traditional impermeable narrow tube, such as the conical tube, undermines the differentiation performance and therapeutic potential of differentiated cartilage pellet in defective articular cartilage treatment. To address this drawback, a perichondrium-inspired permeable nanofibrous tube (PINaT) well with a nanofibrous wall permeable to gas and soluble molecules is proposed. The PINaT well was fabricated with a micro deep drawing process where a flat thin nanofibrous membrane was transformed to a 3.5 mm deep tube well with a ∼50 µm thick nanofibrous wall. Similar to in vivo perichondrium, the PINaT well was found to allow oxygen and growth factor diffusion required for chondrogenic differentiation across the entire nanofibrous wall. Analyses of gene expressions (COL2A1, COL10A1, ACAN, and SOX9), proteins (type II and X collagen), and glycosaminoglycans contents were conducted to assess the differentiation performance and clinical efficacy of differentiated cartilage pellet. The regulated spatially homogeneous chondrogenic microenvironment around the human induced pluripotent stem cell-derived pellet (3 × 105 cells per pellet) in the PINaT well remarkably improved the quality of the differentiated pellet toward a more hyaline-like cartilage pellet. Furthermore, an accelerated chondrogenic differentiation process of the pellet produced by the PINaT well was achieved for 14 days, demonstrating a hyaline cartilage-specific marker similar to the control pellet differentiated for 20 days. Finally, the enhanced clinical efficacy of the hyaline-like cartilage pellet was confirmed using an osteochondral defect rat model, with the repaired tissue resembling hyaline cartilage rather than fibrous cartilage after 8 weeks of regeneration.
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