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Peer-reviewedCC BYCarbohydrate Polymers

Integrating heparan sulfate mimetics into LbL nanofilms as extracellular matrix-like architectures to promote bone tissue regeneration

Abstract

Biomimetic surfaces are increasingly needed to enhance the effectiveness of biomaterials in bone tissue repair. The Layer-by-Layer (LbL) technique is a particularly attractive method due to its versatility and ability to incorporate a wide range of bioactive molecules under mild conditions. While numerous LbL systems have been developed, those integrating glycosaminoglycans (GAG) are often reported to rapidly degrade, which limits their potential in tissue integration. To address this limitation, we investigated the incorporation of ReGeneraTing Agents® (RGTA®) into LbLs. RGTA® are glycanase-resistant analogues of heparan sulfate, designed to protect and stabilize growth factors. To date, their use is restricted to soluble formulations or adsorptions onto biomaterial surfaces. Here, we propose a novel approach to immobilize two RGTA® (OTR4120 and OTR4131) within LbL architectures to produce bone extracellular matrix-like microenvironments. We revealed that OTR4120 potentiated much more in vitro bone formation over OTR4131, with the synthesis of a mature mineralized hydroxyapatite-rich matrix only atop OTR4120 films. Subsequent in vivo translation of OTR4120 LbL films validated the osteogenic potentializing effect. This new strategy aimed at combining the regenerative potential of OTR4120 with the structural and functional advantages of the LbL assemblies, offering a new avenue for the development of biomimetic osteogenic materials.

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BibTeX
@article{bulliermarchandin2026integrating,
  title = {{Integrating heparan sulfate mimetics into LbL nanofilms as extracellular matrix-like architectures to promote bone tissue regeneration}},
  author = {E. Bullier-Marchandin and L. Rossignol and A. Echalard and S. Morin-Grognet and J. Maucotel and A. Arabo and D. Barritault and G. Ladam and B. Labat},
  journal = {Carbohydrate Polymers},
  year = {2026},
  month = sep,
  doi = {10.1016/j.carbpol.2026.124922},
  url = {https://hal.science/hal-05765237v1},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Integrating heparan sulfate mimetics into LbL nanofilms as extracellular matrix-like architectures to promote bone tissue regeneration
AU  - E. Bullier-Marchandin
AU  - L. Rossignol
AU  - A. Echalard
AU  - S. Morin-Grognet
AU  - J. Maucotel
AU  - A. Arabo
AU  - D. Barritault
AU  - G. Ladam
AU  - B. Labat
PY  - 2026
DA  - 2026/09/25
JO  - Carbohydrate Polymers
DO  - 10.1016/j.carbpol.2026.124922
UR  - https://hal.science/hal-05765237v1
AB  - Biomimetic surfaces are increasingly needed to enhance the effectiveness of biomaterials in bone tissue repair. The Layer-by-Layer (LbL) technique is a particularly attractive method due to its versatility and ability to incorporate a wide range of bioactive molecules under mild conditions. While numerous LbL systems have been developed, those integrating glycosaminoglycans (GAG) are often reported to rapidly degrade, which limits their potential in tissue integration. To address this limitation, we investigated the incorporation of ReGeneraTing Agents® (RGTA®) into LbLs. RGTA® are glycanase-resistant analogues of heparan sulfate, designed to protect and stabilize growth factors. To date, their use is restricted to soluble formulations or adsorptions onto biomaterial surfaces. Here, we propose a novel approach to immobilize two RGTA® (OTR4120 and OTR4131) within LbL architectures to produce bone extracellular matrix-like microenvironments. We revealed that OTR4120 potentiated much more in vitro bone formation over OTR4131, with the synthesis of a mature mineralized hydroxyapatite-rich matrix only atop OTR4120 films. Subsequent in vivo translation of OTR4120 LbL films validated the osteogenic potentializing effect. This new strategy aimed at combining the regenerative potential of OTR4120 with the structural and functional advantages of the LbL assemblies, offering a new avenue for the development of biomimetic osteogenic materials.
SN  - 0144-8617
SN  - 1879-1344
ER  -