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고희승Rachel H. Koh

서울대학교

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Bioact. Mater., Available online 14 June 2024 | https://doi.org/10.1016/j.bioactmat.2024.06.018 Bioceramic-mediated chondrocyte hypertrophy promotes calcified cartilage formation for rabbit osteochondral defect repair

Rachel H. Koh^a, Junhee Kim ^a, Jeong-Uk Kim ^a, Seunghyun L. Kim ^b, Arun Kumar Rajendran^a, Seunghun S. Lee ^c, Heesoo Lee ^a, Joo Hyun Kim ^d,e, Ji Hoon Jeong ^d,e, Yongsung Hwang ^d,e, Jong Woo Bae ^f, Nathaniel S. Hwang^a,b,g

^aSchool of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul, 08826, South Korea

^bInterdisciplinary Program in Bioengineering, Seoul National University, Seoul, 08826, South Korea

^cDepartment of Biomedical Engineering, Dongguk University, Seoul, 10326, South Korea

^dSoonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, Cheonan, 31151, South Korea

^eDepartment of Integrated Biomedical Science, Soonchunhyang University, Asan, 31538, South Korea

^fDepartment of Orthopaedic Surgery, Konkuk University Chungju Hospital, Konkuk University School of Medicine, Chungju, 27376, South Korea

^gBioMAX Institute, Seoul National University, Seoul, 08826, South Korea

Corresponding authors: Jong Woo Bae, Nathaniel S. Hwang

Abstract

Osteochondral tissue is a highly specialized and complex tissue composed of articular cartilage and subchondral bone that are separated by a calcified cartilage interface. Multilayered or gradient scaffolds, often in conjunction with stem cells and growth factors, have been developed to mimic the respective layers for osteochondral defect repair. In this study, we designed a hyaline cartilage-hypertrophic cartilage bilayer graft (RGD/RGDW) with chondrocytes. Previously, we demonstrated that RGD peptide-modified chondroitin sulfate cryogel (RGD group) is chondro-conductive and capable of hyaline cartilage formation. Here, we incorporated whitlockite (WH), a Mg ²⁺-containing calcium phosphate, into RGD cryogel (RGDW group) to induce chondrocyte hypertrophy and form collagen X-rich hypertrophic cartilage. This is the first study to use WH to produce hypertrophic cartilage. Chondrocytes-laden RGDW cryogel exhibited significantly upregulated expression of hypertrophy markers in vitro and formed ectopic hypertrophic cartilage in vivo, which mineralized into calcified cartilage in bone microenvironment. Subsequently, RGD cryogel and RGDW cryogel were combined into bilayer (RGD/RGDW group) and implanted into rabbit osteochondral defect, where RGD layer supports hyaline cartilage regeneration and bioceramic-containing RGDW layer promotes calcified cartilage formation. While the RGD group (monolayer) formed hyaline-like neotissue that extends into the subchondral bone, the RGD/RGDW group (bilayer) regenerated hyaline cartilage tissue confined to its respective layer and promoted osseointegration for integrative defect repair.

논문정보

형식Research article
게재일2024년 06월 (BRIC 등록일 2024-07-10)
연구진국내 연구진
분야 바이오·의료융합 > 바이오소재

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