Sustained release of a synthetic structurally-tailored glycopolymer modulates endothelial cells for enhanced endothelialization of materials
| Autor: | Yingjie Hang, Qi Liu, Jingxian Wu, John L. Brash, Hong Chen, Dan Li, Shuaibing Jiang |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Glycopolymer
Basic fibroblast growth factor Biomedical Engineering 02 engineering and technology General Chemistry General Medicine 010402 general chemistry 021001 nanoscience & nanotechnology 01 natural sciences Controlled release 0104 chemical sciences Glycosaminoglycan Endothelial stem cell Cell membrane chemistry.chemical_compound medicine.anatomical_structure Sulfonate chemistry Polycaprolactone medicine Biophysics General Materials Science 0210 nano-technology |
| Zdroj: | Journal of Materials Chemistry B. 7:4017-4029 |
| ISSN: | 2050-7518 2050-750X |
| DOI: | 10.1039/c9tb00714h |
| Popis: | Glycosaminoglycans (GAG) play a vital role in the regulation of various cellular functions through their interactions with key proteins involved in cell signaling and can be useful as bioactive agents in the design of biomaterials. However available “natural” GAG that might be used for this purpose suffer a number of drawbacks including structural heterogeneity and the presence of impurities. Alternatively, GAG-mimicking polymers have shown promise for the modification of biomaterials to support the behavior and function of adherent cells. In the study reported herein, a series of glycopolymers of tailored structure were synthesized using a novel “unit-recombination” strategy. These were intended as surface modifiers for the promotion of surface endothelialization. Two key structural units, sulfonate and saccharide, from the building blocks of GAG, were “recombined” to give GAG analogues by copolymerization of sodium 4-vinylbenzenesulfonate (as the sulfonate unit) and 2-methacrylamido glucopyranose (as the saccharide unit). The composition and molecular weight of the copolymers were adjusted to obtain maximum endothelial cell (EC) proliferation. The glycopolymer with sulfonate and saccharide units in a ratio of approximately 1.0 and a molecular weight of 9.8 kDa was found to be optimal. Interestingly, the data emphasized the key role of saccharide units in GAG bioactivity, rather than the commonly believed decisive role of sulfonate units. The optimized glycopolymer was incorporated into fibrous polycaprolactone (PCL) materials by coaxial electrospinning. These materials showed controlled release of the GAG-mimicking polymers over prolonged periods. The proliferation, migration and function of EC on the glycopolymer-modified PCL fiber mats were greatly improved compared to those on unmodified PCL mats. A likely mechanism underlying these improvements is that the glycopolymers significantly enhance the binding of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) to their receptors on the cell membrane. These findings demonstrate that these structurally-tailored glycopolymers modulate the functions of EC adherent to materials and may be effective as modifiers for the promotion of endothelialization of blood-contacting implants. |
| Databáze: | OpenAIRE |
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