Anti-angiogenic potential of VEGF blocker dendron-laden gellan gum hydrogels for tissue engineering applications
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/43590 |
Resumo: | Damage of non-vascularised tissues such as cartilage and cornea can result in healing processes accompanied by a non-physiological angiogenesis. Peptidic aptamers have recently been reported to block the vascular endothelial growth factor (VEGF). However, the therapeutic applications of these aptamers is limited due to their short half-life in vivo. In this work, an enhanced stability and bioavailability of a known VEGF blocker aptamer sequence (WHLPFKC) was pursued through its tethering of molecular scaffolds based on hyperbranched peptides, the poly(É -lysine) dendrons, bearing three branching generations. The proposed design allowed simultaneous and orderly-spaced exposure of sixteen aptamers per dendrimer to the surrounding biological microenvironent, as well as a relatively hydrophobic core based on di-phenylalanine aiming to promote an hydrophobic interaction with the hydrophobic moieties of ionically-crosslinked metacrylated gellan gum (iGG-MA) hydrogels. The VEGF blocker dendrons were entrapped in iGG-MA hydrogels and their capacity to prevent endothelial cell sprouting was assessed qualitatively and quantitatively using 3D in vitro models and the in vivo chick chorioallantoic membrane (CAM) assay. The data demonstrate that at nanoscale concentrations, the dendronised structures were able to enhance control of the biological actvity of WHLPFKC at the material/tissue interface and hence the anti-angiogenic capacity of iGG-MA hydrogels not only preventing blood vessel invasion, but also inducing their regression at the tissue/iGG-MA interface. The in ovo study confirmed that iGG-MA functionalised with the dendron VEGF blockers do inhibit angiogenesis by controlling both size and ramifications of blood vessels in proximity of the implanted gel surface. |
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Anti-angiogenic potential of VEGF blocker dendron-laden gellan gum hydrogels for tissue engineering applicationsAnti-angiogenic dendronsIVD regenerationAngiogenesisAnti-angiogenesis peptideDendronGellan gumTissue regenerationVascular endothelial growth factorDamage of non-vascularised tissues such as cartilage and cornea can result in healing processes accompanied by a non-physiological angiogenesis. Peptidic aptamers have recently been reported to block the vascular endothelial growth factor (VEGF). However, the therapeutic applications of these aptamers is limited due to their short half-life in vivo. In this work, an enhanced stability and bioavailability of a known VEGF blocker aptamer sequence (WHLPFKC) was pursued through its tethering of molecular scaffolds based on hyperbranched peptides, the poly(É -lysine) dendrons, bearing three branching generations. The proposed design allowed simultaneous and orderly-spaced exposure of sixteen aptamers per dendrimer to the surrounding biological microenvironent, as well as a relatively hydrophobic core based on di-phenylalanine aiming to promote an hydrophobic interaction with the hydrophobic moieties of ionically-crosslinked metacrylated gellan gum (iGG-MA) hydrogels. The VEGF blocker dendrons were entrapped in iGG-MA hydrogels and their capacity to prevent endothelial cell sprouting was assessed qualitatively and quantitatively using 3D in vitro models and the in vivo chick chorioallantoic membrane (CAM) assay. The data demonstrate that at nanoscale concentrations, the dendronised structures were able to enhance control of the biological actvity of WHLPFKC at the material/tissue interface and hence the anti-angiogenic capacity of iGG-MA hydrogels not only preventing blood vessel invasion, but also inducing their regression at the tissue/iGG-MA interface. The in ovo study confirmed that iGG-MA functionalised with the dendron VEGF blockers do inhibit angiogenesis by controlling both size and ramifications of blood vessels in proximity of the implanted gel surface.This work was mainly supported by the EC FP7 project Disc Regeneration (Contract No NMP3-LA-2008-213904). This study was also funded by the EC FP7 Programme contract agreement no REGPOT-CT2012-316331-POLARIS.WileyUniversidade do MinhoPerugini, V.Guildford, A.Silva-Correia, JoanaOliveira, J. M.Meikle, S. T.Reis, R. L.Santin, M.20172017-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/43590engPerugini V., Guildford A., Silva-Correia J., Oliveira J. M., Meikle S. T., Reis R. L., Santin M. Anti-angiogenic Potential of VEGF Blocker Dendron-laden Gellan Gum Hydrogels for Tissue Engineering Applications, Journal of Tissue Engineering and Regenerative Medicine, doi:10.1002/term.2340, 2017.1932-700510.1002/term.2340info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:47:27Zoai:repositorium.sdum.uminho.pt:1822/43590Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:45:34.172912Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Anti-angiogenic potential of VEGF blocker dendron-laden gellan gum hydrogels for tissue engineering applications |
title |
Anti-angiogenic potential of VEGF blocker dendron-laden gellan gum hydrogels for tissue engineering applications |
spellingShingle |
Anti-angiogenic potential of VEGF blocker dendron-laden gellan gum hydrogels for tissue engineering applications Perugini, V. Anti-angiogenic dendrons IVD regeneration Angiogenesis Anti-angiogenesis peptide Dendron Gellan gum Tissue regeneration Vascular endothelial growth factor |
title_short |
Anti-angiogenic potential of VEGF blocker dendron-laden gellan gum hydrogels for tissue engineering applications |
title_full |
Anti-angiogenic potential of VEGF blocker dendron-laden gellan gum hydrogels for tissue engineering applications |
title_fullStr |
Anti-angiogenic potential of VEGF blocker dendron-laden gellan gum hydrogels for tissue engineering applications |
title_full_unstemmed |
Anti-angiogenic potential of VEGF blocker dendron-laden gellan gum hydrogels for tissue engineering applications |
title_sort |
Anti-angiogenic potential of VEGF blocker dendron-laden gellan gum hydrogels for tissue engineering applications |
author |
Perugini, V. |
author_facet |
Perugini, V. Guildford, A. Silva-Correia, Joana Oliveira, J. M. Meikle, S. T. Reis, R. L. Santin, M. |
author_role |
author |
author2 |
Guildford, A. Silva-Correia, Joana Oliveira, J. M. Meikle, S. T. Reis, R. L. Santin, M. |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Perugini, V. Guildford, A. Silva-Correia, Joana Oliveira, J. M. Meikle, S. T. Reis, R. L. Santin, M. |
dc.subject.por.fl_str_mv |
Anti-angiogenic dendrons IVD regeneration Angiogenesis Anti-angiogenesis peptide Dendron Gellan gum Tissue regeneration Vascular endothelial growth factor |
topic |
Anti-angiogenic dendrons IVD regeneration Angiogenesis Anti-angiogenesis peptide Dendron Gellan gum Tissue regeneration Vascular endothelial growth factor |
description |
Damage of non-vascularised tissues such as cartilage and cornea can result in healing processes accompanied by a non-physiological angiogenesis. Peptidic aptamers have recently been reported to block the vascular endothelial growth factor (VEGF). However, the therapeutic applications of these aptamers is limited due to their short half-life in vivo. In this work, an enhanced stability and bioavailability of a known VEGF blocker aptamer sequence (WHLPFKC) was pursued through its tethering of molecular scaffolds based on hyperbranched peptides, the poly(É -lysine) dendrons, bearing three branching generations. The proposed design allowed simultaneous and orderly-spaced exposure of sixteen aptamers per dendrimer to the surrounding biological microenvironent, as well as a relatively hydrophobic core based on di-phenylalanine aiming to promote an hydrophobic interaction with the hydrophobic moieties of ionically-crosslinked metacrylated gellan gum (iGG-MA) hydrogels. The VEGF blocker dendrons were entrapped in iGG-MA hydrogels and their capacity to prevent endothelial cell sprouting was assessed qualitatively and quantitatively using 3D in vitro models and the in vivo chick chorioallantoic membrane (CAM) assay. The data demonstrate that at nanoscale concentrations, the dendronised structures were able to enhance control of the biological actvity of WHLPFKC at the material/tissue interface and hence the anti-angiogenic capacity of iGG-MA hydrogels not only preventing blood vessel invasion, but also inducing their regression at the tissue/iGG-MA interface. The in ovo study confirmed that iGG-MA functionalised with the dendron VEGF blockers do inhibit angiogenesis by controlling both size and ramifications of blood vessels in proximity of the implanted gel surface. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017 2017-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1822/43590 |
url |
http://hdl.handle.net/1822/43590 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Perugini V., Guildford A., Silva-Correia J., Oliveira J. M., Meikle S. T., Reis R. L., Santin M. Anti-angiogenic Potential of VEGF Blocker Dendron-laden Gellan Gum Hydrogels for Tissue Engineering Applications, Journal of Tissue Engineering and Regenerative Medicine, doi:10.1002/term.2340, 2017. 1932-7005 10.1002/term.2340 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Wiley |
publisher.none.fl_str_mv |
Wiley |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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