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Adv. Healthc. Mater., May 24 2025, | https://doi.org/10.1002/adhm.202501471
Synovium-on-a-Chip Reveals Fibroblast-Macrophage Crosstalk Underpinning Joint Homeostasis and Evaluation of Gout Therapies
Min Seok Lee 1, Soohyun Kim 1, Jong-Hwan Lee 2, Yoe-Sik Bae 3, Sung Kyun Lee 1
1Center for Infectious Disease Vaccine and Diagnosis Innovation (CEVI), Korea Research Institute of Chemical Technology (KRICT), Daejeon, 34114, Republic of Korea.
2Department of Bionano Engineering, Hanyang University, Ansan, 15588, Republic of Korea.
3Department of Biological Sciences, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
Corresponding Author : Sung Kyun Lee
1Center for Infectious Disease Vaccine and Diagnosis Innovation (CEVI), Korea Research Institute of Chemical Technology (KRICT), Daejeon, 34114, Republic of Korea.
2Department of Bionano Engineering, Hanyang University, Ansan, 15588, Republic of Korea.
3Department of Biological Sciences, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
Corresponding Author : Sung Kyun Lee
Abstract
The synovium maintains joint homeostasis and regulates immune responses through fibroblast-like synoviocytes (FLS) and macrophage-like synoviocytes (MLS). However, investigation of the intricate FLS-MLS interactions is limited by the lack of physiologically relevant in vitro models. Here, this work presents a synovium-on-a-chip model that faithfully mimics the structural and functional properties of the human synovial lining, established with collagen/alginate hybrid hydrogel (CAHG). The functional phenotype of FLS observed in vivo is replicated on chip when cultured with CAHG. Moreover, co-culture with M2c macrophages derived from CD14+ monocytes enables the reconstruction of key immune functions of the synovial lining, including expression of junction proteins (ZO-1 and CLD5) and immunoregulatory markers (TREM2 and VSIG4). CD44 blockade, disrupting FLS-MLS interactions, significantly suppresses inflammasome-related pathways, underscoring the regulatory role of FLS in synovial immune responses. Our model is further validated by modeling gout, where treatment with monosodium urate crystals trigger NLRP3 inflammasome activation, macrophage polarization, and neutrophil extravasation. Pharmacological interventions with MCC950 and entrectinib effectively inhibit the inflammasome activation, demonstrating the platform's utility for preclinical drug evaluation. This synovium-on-a-chip provides a reliable in vitro model for studying synovial inflammation and serves as a valuable tool for the therapeutic discovery of inflammatory joint diseases.
논문정보
- Research article
- 2025년 05월 (BRIC 등록일 2025-05-27)
- 국내 연구진
- 바이오·의료융합 > 바이오·의료융합 기타
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