An enzyme-proof glycan glue for extracellular matrix to ameliorate intervertebral disc degeneration

  • Nat Commun. 2025 Apr 16;16(1):3629. doi: 10.1038/s41467-025-58946-5.
Yu Liu  1 ,  Tzuwei Chao  1 ,  Yuwei Li  1  2 ,  Peng Peng  3 ,  Gaoran Ge  4 ,  Dechun Geng  4 ,  Lei Dong  5  6  7 ,  Chunming Wang  8  9  10
Affiliations
  • 1. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR, China.
  • 2. Zhuhai UM Science and Technology Research Institute (ZUMRI), University of Macau, Hengqin, China.
  • 3. Department of Emergency, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
  • 4. Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
  • 5. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China. [email protected].
  • 6. National Resource Center for Mutant Mice, Nanjing, Jiangsu, China. [email protected].
  • 7. Chemistry and Biomedicine Innovative Center, Nanjing University, Nanjing, Jiangsu, China. [email protected].
  • 8. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR, China. [email protected].
  • 9. Zhuhai UM Science and Technology Research Institute (ZUMRI), University of Macau, Hengqin, China. [email protected].
  • 10. Department of Pharmaceutical Sciences, Faculty of Health Science, University of Macau, Taipa, Macau SAR, China. [email protected].
PMID: 40240357 DOI: 10.1038/s41467-025-58946-5
Abstract

Intervertebral disc degeneration (IDD) remains a global healthcare challenge. Here, by analyzing clinical samples, we discover the loss of milk fat globule-EGF factor 8 (MFG-E8) from the nucleus pulposus (NP) tissue-along with increased enzymatic breakdown of glycosaminoglycans (GAGs)-as an overlooked factor for IDD development. Repairing the degraded NP extracellular matrix (ECM) with a structurally-mimicking glycan glue to enrich MFG-E8 may counter the degeneration. Accordingly, we synthesize a glucomannan octanoate (GMOC) with robust resistance to ECM-cleaving Enzymes, which forms assemblies with MFG-E8 to maintain a healthy NP cell phenotype. GMOC injected into the degenerated intervertebral disc enriches MFG-E8 in situ, leading to NP tissue regeneration in a rat and a rabbit model, which represent two clinical scenarios of pre-surgical intervention and post-surgical regeneration of IDD, respectively. In summary, we report enriching MFG-E8 in ECM with a glycan glue as a mechanism to promote NP regeneration for IDD treatment.

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