Journal article
Click Chemistry-Based Quantification of Extracellular Matrix Turnover for Drug Screening and Regenerative Medicine
Annals of biomedical engineering, Forthcoming
12 May 2026
PMID: 42120803
Abstract
Purpose
To develop and validate a bioorthogonal labeling approach for quantifying ECM remodeling in living cell and tissue culture systems.
Methods
Strain-promoted azide-alkyne (SPAAC) reactions, or copper-free click chemistry, were used to fluorescently label newly synthesized glycan and protein matrix components. ECM synthesis and degradation was quantified in cartilage explants, human mesenchymal stem cells, and SKBR3 breast cancer cells under various external stimuli, including inflammation, mechanical stimulus, and drug treatment.
Results
The click chemistry method reliable quantified ECM turnover across platforms. It detected reduced glycan and protein synthesis after 24-hour inflammatory challenge and enabled longitudinal tracking of ECM degradation in cartilage explants. The technique demonstrated high sensitivity, measuring increased ECM deposition by ~ 10,000 human mesenchymal stem cells in 12-hour intervals and substrate stiffness-dependent synthesis by SKBR3 cells. Additionally, the approach supported osteoarthritis drug screening by identifying compounds that mitigated inflammation-induced ECM degradation.
Conclusion
Compared to traditional biochemical or histological assays, the click chemistry-based technique provides higher sensitivity, reduced sample requirements, and improved temporal resolution for quantifying ECM turnover. Its versatility enables broad application in tissue engineering, regenerative medicine, disease modeling, and high-throughput drug evaluation.
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Details
- Title
- Click Chemistry-Based Quantification of Extracellular Matrix Turnover for Drug Screening and Regenerative Medicine
- Creators
- Annie Porter - University of DelawareSongshan Fan - University of DelawareYing Peng - University of DelawareMengxi Lv - University of DelawareYilu Zhou - University of DelawareAbdulaziz Alanazi - Drexel UniversityLin Han - Drexel UniversityLiyun Wang - University of DelawareX. Lucas Lu (Corresponding Author) - University of Delaware
- Publication Details
- Annals of biomedical engineering, Forthcoming
- Publisher
- Springer Nature
- Number of pages
- 13
- Grant note
- University of Delaware: Helwig Fellowship in Mechanical Engineering U.S. Department of Defense: W81XWH-13-1-0148 National Institutes of Health: R01AR074472, P20GM139760, R01AR074490 National Science Foundation: CMMI-1751898 Division of Graduate Education: Graduate Research Fellowship Program
The authors have no relevant financial or non-financial interests to disclose.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:001764231500001
- Scopus ID
- 2-s2.0-105039319486
- Other Identifier
- 991022179442304721