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Chem. Eng. J., Available online 14 July 2025 | https://doi.org/10.1016/j.cej.2025.165965 Lacuna-mimic human-derived nasal septal chondrocyte clusters encapsulated in click chemistry-based hydrogel for in vivo cartilage regeneration

Jung Ho Jeon ^{a b c 1}, Seo Young Cheon ^{b d 1}, Sun Hwa Park ^c, Hyunji Lee ^{a b c}, Seung-Yeon Yoo ^c, Min Young Ahn ^c, Donghyun Lee ^{b d}, Man Soo Kim ^e, Jeong Hun Park^f, Scott J. Hollister ^f, Heebeom Koo ^{b d *}, Sung Won Kim ^{a b c *}

^aDepartment of Otolaryngology-Head and Neck Surgery, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea
^bDepartment of Medical Sciences (Graduate School), College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea
^cLaboratory for Regeneration of Human Activity with Stem Cells (RHAs), Postech-Catholic Biomedical Engineering Institute, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea
^dDepartment of Medical Life Sciences, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho gu, Seoul 06591, Republic of Korea
^eDepartment of Orthopedic Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
^fWallace H. Coulter Department of Biomedical Engineering and Center for 3D Medical Fabrication, Georgia Institute of Technology and Emory University, 313 Ferst Drive, Atlanta, GA 30332, USA

¹These authors contributed equally

^*Corresponding authors: correspondence to Heebeom Koo or Sung Won Kim

Abstract

In the lacuna structure of cartilage, a small group of chondrocytes are contacted and surrounded by extracellular matrix. To mimic this structure, we applied tannic acid (TA)-based clustering and click chemistry-based hydrogel to our human-derived nasal septal chondrocytes (hNCs) with advantages including easy harvesting from patients, stemness, and superior differentiation capacity. We fabricated lacuna-mimic hNC clusters based on the binding ability of TA. The hNC clusters were encapsulated in a hydrogel crosslinked by click chemistry between modified polyethylene glycol (PEG) and gelatin. The hNC clusters showed high viability and improved chondrogenic differentiation in click chemistry-based hydrogel. When we injected the hNC clusters in hydrogel into a rat osteochondral defect model, they resulted in successful regeneration of cartilage in immunohistochemical staining data. These results demonstrate the potential of the lacuna-mimic structure composed of hNC clusters and click chemistry-based hydrogel in cartilage regeneration in vivo.

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