2. Academic Validation
  3. Accelerating cartilage regeneration with DNA-SF hydrogel sustained release system-based cartilage organoids

Accelerating cartilage regeneration with DNA-SF hydrogel sustained release system-based cartilage organoids

  • Mil Med Res. 2025 Jul 28;12(1):39. doi: 10.1186/s40779-025-00625-z.
Cong-Yi Shen # 1 2 3 4 5,  Qi-Rong Zhou # 6,  Xiang Wu # 1 2 3 4 5,  Xin-Yu Han # 1 2 3 4 5,  Qin Zhang 1 2 3 5,  Xiao Chen 1 2 3 5 6,  Yu-Xiao Lai 7,  Long Bai 1 2 3 5,  Ying-Ying Jing 1 2 3 5,  Jian-Hua Wang 8,  Cheng-Long Wang 9,  Zhen Geng 10 11 12 13,  Jia-Can Su 14 15 16 17 18
Affiliations

Affiliations

  • 1 Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China.
  • 2 MedEng-X Institutes, Shanghai University, Shanghai, 200444, China.
  • 3 Organoid Research Center, Shanghai University, Shanghai, 200444, China.
  • 4 School of Medicine, Shanghai University, Shanghai, 200444, China.
  • 5 National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, 200444, China.
  • 6 Department of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
  • 7 Centre for Translational Medicine Research and Development, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, Guangdong, China.
  • 8 Department of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China. shwangjianhua@gmail.com.
  • 9 Department of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China. wangorth@163.com.
  • 10 Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China. nanboshan1987@163.com.
  • 11 MedEng-X Institutes, Shanghai University, Shanghai, 200444, China. nanboshan1987@163.com.
  • 12 Organoid Research Center, Shanghai University, Shanghai, 200444, China. nanboshan1987@163.com.
  • 13 National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, 200444, China. nanboshan1987@163.com.
  • 14 Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China. drsujiacan@163.com.
  • 15 MedEng-X Institutes, Shanghai University, Shanghai, 200444, China. drsujiacan@163.com.
  • 16 Organoid Research Center, Shanghai University, Shanghai, 200444, China. drsujiacan@163.com.
  • 17 National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, 200444, China. drsujiacan@163.com.
  • 18 Department of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China. drsujiacan@163.com.
  • # Contributed equally.
PMID: 40722047 DOI: 10.1186/s40779-025-00625-z
Abstract

Background: Cartilage repair remains a considerable challenge in regenerative medicine. Despite extensive research on biomaterials for cartilage repair in recent years, issues such as prolonged repair cycles and suboptimal outcomes persist. Organoids, miniature three-dimensional (3D) tissue structures derived from the directed differentiation of stem or progenitor cells, mimic the structure and function of natural organs. Therefore, the construction of cartilage organoids (COs) holds great promise as a novel strategy for cartilage repair.

Methods: This study employed a digital light processing system to perform 3D bioprinting of a DNA-silk fibroin (DNA-SF) hydrogel sustained-release system (DSRGT) with bone-marrow mesenchymal stem cells (BMSCs) to construct millimeter-scale cerebral organoids. COs at different developmental stages were characterized, and the COs with the best cartilage phenotype were selected for in vivo cartilage repair in a rat articular cartilage defect model.

Results: This study developed a DSRGT by covalently grafting glucosamine (which promotes cartilage matrix synthesis) and TD-198946 (which promotes chondrogenic differentiation) onto a hydrogel using acrylic acid-polyethylene glycol-N-hydroxysuccinimide (AC-PEG-NHS). In vitro, 4-week COs exhibited higher SRY-box transcription factor 9 (SOX9), type II Collagen (Col II), and aggrecan (ACAN) expression and lower type I Collagen (Col I) and type X Collagen (Col X) expression, indicating that 4 weeks is the optimal culture duration for hyaline cartilage development. In vivo, the mitogen-activated protein kinase (MAPK) signaling pathway was upregulated in 4-week COs, enabling cartilage repair within 8 weeks. Transcriptomic analysis revealed that cartilage regenerated with 4-week COs presented gene expression profiles resembling those of healthy cartilage.

Conclusions: This study employs DSRGT to construct COs, providing an innovative strategy for the regeneration of cartilage defects.

Keywords

Cartilage organoid (COs); Cartilage repair; Chondrogenesis; DNA-silk fibroin hydrogel; Glucosamine; TD-198946.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z