Guiding stem cell tenogenesis by modulation of growth factor signaling and cell-scale biophysical cues in bioengineered constructs
Autor(a) principal: | |
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Data de Publicação: | 2024 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://hdl.handle.net/1822/89123 |
Resumo: | Tendon injuries and tendinopathies are increasingly prevalent health problems currently lacking effective treatments. Tissue engineering offers promising strategies to boost the low innate regenerative ability of tendons. Within this context, the simultaneous leveraging of both physical and biochemical cues by engineered scaffolding systems can be explored to promote a stronger tenogenic response from stem cells. Here, molecularly imprinted polymeric nanoparticles (MINPs) against transforming growth factor (TGF)-β3 are combined with bioinspired anisotropic hydrogels to produce tenogenesis-inductive constructs. MINPs are first solid phase-imprinted against a TGF-β3 epitope, achieving an affinity comparable to monoclonal antibodies. MINPs and magnetically-responsive microfibers are then encapsulated together with adipose-derived stem cells within gelatin-based hydrogels, applying a magnetostatic field during gelation to align the microfibers. The created anisotropic microstructure guides cell growth and elongation unidirectionally, while MINPs act as artificial receptors for TGF-β3, potentiating its paracrine action in the cellular microenvironment. The combination of both stimuli proves effective at increasing TGF-β signaling, which promotes the expression of tendon-associated genes and corresponding protein synthesis, suggesting that microstructural cues and biomolecule sequestration act in tandem to direct cell fate commitment. Overall, this system recapitulates several elements of tendon development, constituting a promising strategy for the regeneration of this tissue. |
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Guiding stem cell tenogenesis by modulation of growth factor signaling and cell-scale biophysical cues in bioengineered constructsBiomimeticsGrowth factorsHydrogelsMicrostructuresMolecular imprintingTendon injuries and tendinopathies are increasingly prevalent health problems currently lacking effective treatments. Tissue engineering offers promising strategies to boost the low innate regenerative ability of tendons. Within this context, the simultaneous leveraging of both physical and biochemical cues by engineered scaffolding systems can be explored to promote a stronger tenogenic response from stem cells. Here, molecularly imprinted polymeric nanoparticles (MINPs) against transforming growth factor (TGF)-β3 are combined with bioinspired anisotropic hydrogels to produce tenogenesis-inductive constructs. MINPs are first solid phase-imprinted against a TGF-β3 epitope, achieving an affinity comparable to monoclonal antibodies. MINPs and magnetically-responsive microfibers are then encapsulated together with adipose-derived stem cells within gelatin-based hydrogels, applying a magnetostatic field during gelation to align the microfibers. The created anisotropic microstructure guides cell growth and elongation unidirectionally, while MINPs act as artificial receptors for TGF-β3, potentiating its paracrine action in the cellular microenvironment. The combination of both stimuli proves effective at increasing TGF-β signaling, which promotes the expression of tendon-associated genes and corresponding protein synthesis, suggesting that microstructural cues and biomolecule sequestration act in tandem to direct cell fate commitment. Overall, this system recapitulates several elements of tendon development, constituting a promising strategy for the regeneration of this tissue.Wiley-VCH GmbHUniversidade do MinhoTeixeira, Simão P. B.Pardo, AlbertoBakht, Syeda M.Gómez-Florit, ManuelReis, R. L.Gomes, Manuela E.Domingues, Rui Miguel Andrade2024-022024-02-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/1822/89123engTeixeira S. P. B., Pardo A., Bakht S. M., Gómez-Florit M., Reis R. L., Gomes M. E., Domingues R. M. A. Guiding stem cell tenogenesis by modulation of growth factor signaling and cell-scale biophysical cues in bioengineered constructs, Advanced Functional Materials, pp. 2312961, doi:10.1002/adfm.202312961, 20241616-302810.1002/adfm.202312961https://onlinelibrary.wiley.com/doi/10.1002/adfm.202312961info: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:RCAAP2024-03-02T01:19:21Zoai:repositorium.sdum.uminho.pt:1822/89123Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:11:44.029681Repositório 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 |
Guiding stem cell tenogenesis by modulation of growth factor signaling and cell-scale biophysical cues in bioengineered constructs |
title |
Guiding stem cell tenogenesis by modulation of growth factor signaling and cell-scale biophysical cues in bioengineered constructs |
spellingShingle |
Guiding stem cell tenogenesis by modulation of growth factor signaling and cell-scale biophysical cues in bioengineered constructs Teixeira, Simão P. B. Biomimetics Growth factors Hydrogels Microstructures Molecular imprinting |
title_short |
Guiding stem cell tenogenesis by modulation of growth factor signaling and cell-scale biophysical cues in bioengineered constructs |
title_full |
Guiding stem cell tenogenesis by modulation of growth factor signaling and cell-scale biophysical cues in bioengineered constructs |
title_fullStr |
Guiding stem cell tenogenesis by modulation of growth factor signaling and cell-scale biophysical cues in bioengineered constructs |
title_full_unstemmed |
Guiding stem cell tenogenesis by modulation of growth factor signaling and cell-scale biophysical cues in bioengineered constructs |
title_sort |
Guiding stem cell tenogenesis by modulation of growth factor signaling and cell-scale biophysical cues in bioengineered constructs |
author |
Teixeira, Simão P. B. |
author_facet |
Teixeira, Simão P. B. Pardo, Alberto Bakht, Syeda M. Gómez-Florit, Manuel Reis, R. L. Gomes, Manuela E. Domingues, Rui Miguel Andrade |
author_role |
author |
author2 |
Pardo, Alberto Bakht, Syeda M. Gómez-Florit, Manuel Reis, R. L. Gomes, Manuela E. Domingues, Rui Miguel Andrade |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Teixeira, Simão P. B. Pardo, Alberto Bakht, Syeda M. Gómez-Florit, Manuel Reis, R. L. Gomes, Manuela E. Domingues, Rui Miguel Andrade |
dc.subject.por.fl_str_mv |
Biomimetics Growth factors Hydrogels Microstructures Molecular imprinting |
topic |
Biomimetics Growth factors Hydrogels Microstructures Molecular imprinting |
description |
Tendon injuries and tendinopathies are increasingly prevalent health problems currently lacking effective treatments. Tissue engineering offers promising strategies to boost the low innate regenerative ability of tendons. Within this context, the simultaneous leveraging of both physical and biochemical cues by engineered scaffolding systems can be explored to promote a stronger tenogenic response from stem cells. Here, molecularly imprinted polymeric nanoparticles (MINPs) against transforming growth factor (TGF)-β3 are combined with bioinspired anisotropic hydrogels to produce tenogenesis-inductive constructs. MINPs are first solid phase-imprinted against a TGF-β3 epitope, achieving an affinity comparable to monoclonal antibodies. MINPs and magnetically-responsive microfibers are then encapsulated together with adipose-derived stem cells within gelatin-based hydrogels, applying a magnetostatic field during gelation to align the microfibers. The created anisotropic microstructure guides cell growth and elongation unidirectionally, while MINPs act as artificial receptors for TGF-β3, potentiating its paracrine action in the cellular microenvironment. The combination of both stimuli proves effective at increasing TGF-β signaling, which promotes the expression of tendon-associated genes and corresponding protein synthesis, suggesting that microstructural cues and biomolecule sequestration act in tandem to direct cell fate commitment. Overall, this system recapitulates several elements of tendon development, constituting a promising strategy for the regeneration of this tissue. |
publishDate |
2024 |
dc.date.none.fl_str_mv |
2024-02 2024-02-01T00:00:00Z |
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 |
https://hdl.handle.net/1822/89123 |
url |
https://hdl.handle.net/1822/89123 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Teixeira S. P. B., Pardo A., Bakht S. M., Gómez-Florit M., Reis R. L., Gomes M. E., Domingues R. M. A. Guiding stem cell tenogenesis by modulation of growth factor signaling and cell-scale biophysical cues in bioengineered constructs, Advanced Functional Materials, pp. 2312961, doi:10.1002/adfm.202312961, 2024 1616-3028 10.1002/adfm.202312961 https://onlinelibrary.wiley.com/doi/10.1002/adfm.202312961 |
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-VCH GmbH |
publisher.none.fl_str_mv |
Wiley-VCH GmbH |
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 |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799137767398047744 |