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Controlled release of TGF-beta 1 from RADA self-assembling peptide hydrogel scaffolds

View Article: PubMed Central - PubMed

ABSTRACT

Bioactive mediators, cytokines, and chemokines have an important role in regulating and optimizing the synergistic action of materials, cells, and cellular microenvironments for tissue engineering. RADA self-assembling peptide hydrogels have been proved to have an excellent ability to promote cell proliferation, wound healing, tissue repair, and drug delivery. Here, we report that D-RADA16 and L-RADA16-RGD self-assembling peptides can form stable second structure and hydrogel scaffolds, affording the slow release of growth factor (transforming growth factor cytokine-beta 1 [TGF-beta 1]). In vitro tests demonstrated that the plateau release amount can be obtained till 72 hours. Moreover, L-RADA16, D-RADA16, and L-RADA16-RGD self-assembling peptide hydrogels containing TGF-beta 1 were used for 3D cell culture of bone mesenchymal stem cells of rats for 2 weeks. The results revealed that these three RADA16 peptide hydrogels had a significantly favorable influence on proliferation of bone mesenchymal stem cells and hold some promise in slow and sustained release of growth factor.

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Proliferation effect of released TGF-beta 1 over bone mesenchymal stem cells.Notes: The cells and RADA16 hydrogels contained TGF were co-cultured for 3 days (A), 7 days (B), and 14 days (C). CCK-8 assay for proliferated progeny (n=5). In the case of L-RADA16, a long-term effect of released TGF-beta 1 is evidenced by significantly higher total cell population. The TGF-beta 1 mitogenic activity can be appreciated till 2 weeks after being mixed with the self-assembling scaffolds. *P<0.05.Abbreviations: TGF, transforming growth factor; OD, optical density.
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f6-dddt-10-3043: Proliferation effect of released TGF-beta 1 over bone mesenchymal stem cells.Notes: The cells and RADA16 hydrogels contained TGF were co-cultured for 3 days (A), 7 days (B), and 14 days (C). CCK-8 assay for proliferated progeny (n=5). In the case of L-RADA16, a long-term effect of released TGF-beta 1 is evidenced by significantly higher total cell population. The TGF-beta 1 mitogenic activity can be appreciated till 2 weeks after being mixed with the self-assembling scaffolds. *P<0.05.Abbreviations: TGF, transforming growth factor; OD, optical density.

Mentions: TGF-beta 1 has been proven to have the ability to stimulate and promote proliferation of BMSC by adjusting mitotic process. To assess the activity of the TGF-beta 1 released from the RADA peptide hydrogel scaffolds CCK-8 assay was used (Figure 6), which indicated that there was enhanced proliferation of BMSC on L-RADA16, D-RADA16, and L-RADA16-RGD scaffolds, especially on L-RADA16 scaffolds incorporating TGF-beta 1, whereas the proliferation of BMSC cultured on RADA16 scaffolds was not significantly different from the control group. Collectively, asymptotical delivery of TGF-beta 1 from these peptide scaffolds was shown within the first 8 hours, and after that initial burst and similar release continued for the next days on condition that the whole release systems should not be disturbed and the diffused and released TGF-beta 1 should be kept in balance. The initial burst release might also be affected by the covered TGF-beta 1 on the surface peptide scaffolds. This result suggested that the release effect of active TGF-beta 1 was possibly able to continue for at least 2 weeks till the storage of the diffused growth factor was exhausted, and the electrostatic charges in the self-assembling nanofibers may interact with the TGF. These findings may be helpful for tissue regeneration strategies with sustained release of TGF-beta 1 to stimulate and promote the chondrogenesis or osteogenesis.


Controlled release of TGF-beta 1 from RADA self-assembling peptide hydrogel scaffolds
Proliferation effect of released TGF-beta 1 over bone mesenchymal stem cells.Notes: The cells and RADA16 hydrogels contained TGF were co-cultured for 3 days (A), 7 days (B), and 14 days (C). CCK-8 assay for proliferated progeny (n=5). In the case of L-RADA16, a long-term effect of released TGF-beta 1 is evidenced by significantly higher total cell population. The TGF-beta 1 mitogenic activity can be appreciated till 2 weeks after being mixed with the self-assembling scaffolds. *P<0.05.Abbreviations: TGF, transforming growth factor; OD, optical density.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5036568&req=5

f6-dddt-10-3043: Proliferation effect of released TGF-beta 1 over bone mesenchymal stem cells.Notes: The cells and RADA16 hydrogels contained TGF were co-cultured for 3 days (A), 7 days (B), and 14 days (C). CCK-8 assay for proliferated progeny (n=5). In the case of L-RADA16, a long-term effect of released TGF-beta 1 is evidenced by significantly higher total cell population. The TGF-beta 1 mitogenic activity can be appreciated till 2 weeks after being mixed with the self-assembling scaffolds. *P<0.05.Abbreviations: TGF, transforming growth factor; OD, optical density.
Mentions: TGF-beta 1 has been proven to have the ability to stimulate and promote proliferation of BMSC by adjusting mitotic process. To assess the activity of the TGF-beta 1 released from the RADA peptide hydrogel scaffolds CCK-8 assay was used (Figure 6), which indicated that there was enhanced proliferation of BMSC on L-RADA16, D-RADA16, and L-RADA16-RGD scaffolds, especially on L-RADA16 scaffolds incorporating TGF-beta 1, whereas the proliferation of BMSC cultured on RADA16 scaffolds was not significantly different from the control group. Collectively, asymptotical delivery of TGF-beta 1 from these peptide scaffolds was shown within the first 8 hours, and after that initial burst and similar release continued for the next days on condition that the whole release systems should not be disturbed and the diffused and released TGF-beta 1 should be kept in balance. The initial burst release might also be affected by the covered TGF-beta 1 on the surface peptide scaffolds. This result suggested that the release effect of active TGF-beta 1 was possibly able to continue for at least 2 weeks till the storage of the diffused growth factor was exhausted, and the electrostatic charges in the self-assembling nanofibers may interact with the TGF. These findings may be helpful for tissue regeneration strategies with sustained release of TGF-beta 1 to stimulate and promote the chondrogenesis or osteogenesis.

View Article: PubMed Central - PubMed

ABSTRACT

Bioactive mediators, cytokines, and chemokines have an important role in regulating and optimizing the synergistic action of materials, cells, and cellular microenvironments for tissue engineering. RADA self-assembling peptide hydrogels have been proved to have an excellent ability to promote cell proliferation, wound healing, tissue repair, and drug delivery. Here, we report that D-RADA16 and L-RADA16-RGD self-assembling peptides can form stable second structure and hydrogel scaffolds, affording the slow release of growth factor (transforming growth factor cytokine-beta 1 [TGF-beta 1]). In vitro tests demonstrated that the plateau release amount can be obtained till 72 hours. Moreover, L-RADA16, D-RADA16, and L-RADA16-RGD self-assembling peptide hydrogels containing TGF-beta 1 were used for 3D cell culture of bone mesenchymal stem cells of rats for 2 weeks. The results revealed that these three RADA16 peptide hydrogels had a significantly favorable influence on proliferation of bone mesenchymal stem cells and hold some promise in slow and sustained release of growth factor.

No MeSH data available.


Related in: MedlinePlus