AccScience Publishing / OR / Volume 1 / Issue 4 / DOI: 10.36922/OR025480037
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ORIGINAL RESEARCH ARTICLE

Self-organizing vascularized subchondral bone organoids from stromal vascular fraction enable functional osteochondral interface regeneration

Tao Qian1 ,  Jiazhou Wu2 ,  Zexian Liu2,3 ,  Aiyuan Wang2,3 ,  Yanbin Wu2 ,  Junli Wang1 ,  Hongyu Jiang2 ,  Zhengrui Zhou2 ,  Cheng Huang2 ,  Yazhou Li2 ,  Junming Zhang1 ,  Biao Ma1 ,  Yun Bai1 ,  Jialiang You2 ,  Endong Luo2 ,  Dingkai Wang2 ,  Ying He2* ,  Jiang Peng1,2*
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1 The Third Clinical College, Jinzhou Medical University, Jinzhou, Liaoning Province, China
2 Institute of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital, Beijing Key Laboratory of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries, PLA, Beijing, Beijing Municipality, China
3 Graduate School, Chinese PLA General Hospital, Beijing, Beijing Municipality, China
OR 2025, 1(4), 025480037 https://doi.org/10.36922/OR025480037
Received: 30 November 2025 | Revised: 22 December 2025 | Accepted: 25 December 2025 | Published online: 30 December 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Osteoarthritis (OA) is closely associated with subchondral bone (SCB) degeneration; however, current models fail to adequately mimic its complex microenvironment. Here, we developed a self-organizing subchondral bone organoid (SSBO) by co-culturing stromal vascular fraction (SVF) cells with decellularized cartilage extracellular matrix (CECM). SVF provided cellular heterogeneity, including adipose-derived stem cells (ADSCs), endothelial cells, pericytes, and macrophages, while CECM served as a native scaffold with tissue-specific cues. SSBO exhibited spontaneous spheroid formation, active cellular infiltration, and dynamic matrix remodeling. Compared to ADSC-only controls, SSBO showed enhanced cell viability, vascularization, collagen remodeling, and spatial organization. Immunostaining and qPCR analyses confirmed an endochondral ossification-like process, characterized by the sequential expression of SOX9, COL2A1, RUNX2, COL1A1, and OCN. In vivo implantation into immunodeficient mice demonstrated robust angiogenesis, bone-like tissue formation, and integration with host vasculature. Furthermore, in a mouse osteochondral defect model, SSBO significantly promoted repair, with improved bone volume, trabecular architecture, and cartilage regeneration. Collectively, this study presents a novel strategy for constructing vascularized, immunomodulatory, and osteogenic SCB organoids, offering a promising platform for regenerative medicine and bone–cartilage interface repair.

Graphical abstract
Keywords
SVF
Organoids
Tissue engineering
Stromal vascular fraction
Subchondral bone
Funding
This study was supported by the National Key Research and Development Program of China (Grant No. 2024YFA1108600).
Conflict of interest
The authors declare no competing financial interests.
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