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We show that supramolecular polymers based on quadruple hydrogen bonding ureido-pyrimidinone moieties are eminently suitable for producing such bioactive materials owing to their low-temperature processability, favourable degradation and biocompatible behaviour

A modular and supramolecular approach to bioactive scaffolds for tissue engineering

NATURE MATERIALS, no. 7 (2005): 568-574

被引用315|浏览11
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摘要

Bioactive polymeric scaffolds are a prerequisite for the ultimate formation of functional tissues. Here, we show that supramolecular polymers based on quadruple hydrogen bonding ureido- pyrimidinone ( UPy) moieties are eminently suitable for producing such bioactive materials owing to their low- temperature processability, favourable degr...更多

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简介
  • The technique of tissue engineering has become prominent in producing new tissue using polymeric scaffolds and cells[1].
  • Owing to the reversible nature of the hydrogen bonds, the PCLdiUPy material could be processed by different techniques into several scaffolds (Fig. 2) varying from films and fibres to meshes and grids.
重点内容
  • The technique of tissue engineering has become prominent in producing new tissue using polymeric scaffolds and cells[1]
  • We propose here a new materials design by means of specific non-covalent interactions between the polymer and biomolecule that bridges the gap between covalent functionalization and blending of polymers with bioactive molecules. Suitable for producing these novel, tuneable, bioactive materials are supramolecular polymers based on quadruple-hydrogen-bonding 2-ureido-4[1H]-pyrimidinone (UPy) moieties[23,24,25,26] (Fig. 1a). These supramolecular polymers are made of repeating units held together by strong non-covalent nature materials | VOL 4 | JULY 2005 | www.nature.com/naturematerials a b
  • We report here our modular approach to constructing bioactive materials with various properties, which is by mixing UPyfunctionalized polymers with UPy-modified biomolecules (Fig. 1b)
  • If different concentrations of the UPy-GRGDS peptides, 1, 2 or 4 mol%, were swollen on the polymer films made according to method two, hardly any differences in cell adhesion and spreading were observed between the samples
  • The cells cultured on blend 3 without FBS look similar to cells cultured on blend 3 or on the bottom of a polystyrene (PS) culture dish in the presence of FBS after one day of incubation (Fig. 4b). These results indicate that the peptides facilitate cell adhesion and spreading in the same way as extracellular matrix (ECM) proteins in FBS
结果
  • If different concentrations of the UPy-GRGDS peptides, 1, 2 or 4 mol%, were swollen on the polymer films made according to method two, hardly any differences in cell adhesion and spreading were observed between the samples.
  • Controls with peptides without a UPy-unit showed that they were not able to induce cell adhesion and spreading, which was shown for polymer 4 (Fig. 3), confirming the extraction experiments in which the peptides without a UPy-moiety rapidly diffuse out of the film.
  • The presence of water-soluble GRGDS peptides in the medium can influence the binding of the cells to bioactive materials as shown in an inhibition experiment where 3T3 fibroblasts were first incubated with GRGDS peptides before seeding on blend 3 (Fig. 4a).
  • The second set of films was incubated in medium without FBS for three hours before seeding of the cells on the polymers to test nature materials | VOL 4 | JULY 2005 | www.nature.com/naturematerials
  • All these experiments—with and without peptides—show that UPy-peptides are really necessary to promote cell adhesion and spreading in vitro due to the dynamic binding of the peptides to the supramolecular material.
  • Another remarkable difference was the fact that in the case of blend 3 after five days, large giant cells were already budding into the material from the interface (Fig. 5), which indicates that the UPy-GRGDS and UPy-PHSRN peptides may play a part in the signalling and infiltration of macrophages, and in their fusion to giant cells.
  • These materials will be subjected to more intensive studies to elucidate the role of the different peptides on the supramolecular polymer properties and the presence of the UPy-unit in vivo.
结论
  • 3T3 mouse fibroblasts (5 × 104 cells cm–2) were seeded on the cover slips with the supramolecular bioactive materials or with the bare PCLdiUPy, on the bottom of a PS culture dish and on glass in 200 μl medium.
  • IN VIVO IMPLANTATIONS Solution cast PCLdiUPy films without and with 4 mol% of UPy-GRGDS and 4 mol% of UPy-PHSRN were subcutaneously implanted in duplicate into male Albino Oxford rats.
总结
  • The technique of tissue engineering has become prominent in producing new tissue using polymeric scaffolds and cells[1].
  • Owing to the reversible nature of the hydrogen bonds, the PCLdiUPy material could be processed by different techniques into several scaffolds (Fig. 2) varying from films and fibres to meshes and grids.
  • If different concentrations of the UPy-GRGDS peptides, 1, 2 or 4 mol%, were swollen on the polymer films made according to method two, hardly any differences in cell adhesion and spreading were observed between the samples.
  • Controls with peptides without a UPy-unit showed that they were not able to induce cell adhesion and spreading, which was shown for polymer 4 (Fig. 3), confirming the extraction experiments in which the peptides without a UPy-moiety rapidly diffuse out of the film.
  • The presence of water-soluble GRGDS peptides in the medium can influence the binding of the cells to bioactive materials as shown in an inhibition experiment where 3T3 fibroblasts were first incubated with GRGDS peptides before seeding on blend 3 (Fig. 4a).
  • The second set of films was incubated in medium without FBS for three hours before seeding of the cells on the polymers to test nature materials | VOL 4 | JULY 2005 | www.nature.com/naturematerials
  • All these experiments—with and without peptides—show that UPy-peptides are really necessary to promote cell adhesion and spreading in vitro due to the dynamic binding of the peptides to the supramolecular material.
  • Another remarkable difference was the fact that in the case of blend 3 after five days, large giant cells were already budding into the material from the interface (Fig. 5), which indicates that the UPy-GRGDS and UPy-PHSRN peptides may play a part in the signalling and infiltration of macrophages, and in their fusion to giant cells.
  • These materials will be subjected to more intensive studies to elucidate the role of the different peptides on the supramolecular polymer properties and the presence of the UPy-unit in vivo.
  • 3T3 mouse fibroblasts (5 × 104 cells cm–2) were seeded on the cover slips with the supramolecular bioactive materials or with the bare PCLdiUPy, on the bottom of a PS culture dish and on glass in 200 μl medium.
  • IN VIVO IMPLANTATIONS Solution cast PCLdiUPy films without and with 4 mol% of UPy-GRGDS and 4 mol% of UPy-PHSRN were subcutaneously implanted in duplicate into male Albino Oxford rats.
基金
  • This work is supported by the Council for Chemical Sciences of the Netherlands Organization for Scientific Research (CW-NWO)
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