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Biomimetic Glycosaminoglycan Analog Hydrogels Inhibit Neurite Outgrowth While Supporting Neuronal Cell Viability
Khyal Sumaya1, Dar Segev1, Haim S Mordechai2
1Department of Biotechnology Engineering, Braude College of Engineering, Karmiel, Israel.
Journal of Biomedical Materials Research. Part A
|December 4, 2025
Summary
Synthetic GAG analogs show promise for intervertebral disc (IVD) repair by mimicking native tissue and inhibiting nerve growth. These biomaterials effectively reduce neurite extension while maintaining high cell viability, offering a potential solution for chronic low back pain.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Neuroscience
Background:
- Intervertebral disc (IVD) degeneration causes chronic low back pain due to loss of sulfated glycosaminoglycans (sGAGs).
- sGAG depletion leads to dehydration, matrix disorganization, and pathological nerve ingrowth in degenerated discs.
- Synthetic GAG analogs are being explored for IVD repair due to their biomimetic properties.
Purpose of the Study:
- To evaluate the neuroinhibitory potential of synthetic GAG analog hydrogels.
- To assess the effect of varying crosslinking densities on GAG analog function.
- To determine if GAG analogs can prevent pain-related nerve infiltration in IVD degeneration.
Main Methods:
- Cultured SH-SY5Y neuroblastoma cells on GAG analog hydrogels with crosslinking densities from 0.5% to 2%.
- Measured neurite extension lengths.
- Assessed cell viability in the presence and absence of exogenous chondroitin sulfate (CS).
Main Results:
- GAG analogs significantly suppressed neurite extension to <10 μm.
- Control cultures showed significantly longer neurite extensions (79.3 ± 55.8 μm and 157.1 ± 103.8 μm).
- Cell viability remained high (75%-92%) across all tested conditions.
Conclusions:
- Synthetic GAG analogs can mimic the neuroinhibitory properties of native sGAGs.
- These GAG analogs show potential as therapeutic biomaterials for IVD regeneration.
- GAG analogs may prevent pain-related nerve infiltration in degenerated discs.
