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dc.contributor.authorAlmeida, H.por
dc.contributor.authorDomingues, Rui Miguel Andradepor
dc.contributor.authorMithieux, S. M.por
dc.contributor.authorPires, R. A.por
dc.contributor.authorGonçalves, A Ipor
dc.contributor.authorGomez-Florit, Manuelpor
dc.contributor.authorReis, R. L.por
dc.contributor.authorWeiss, A. S.por
dc.contributor.authorGomes, Manuela E.por
dc.identifier.citationAlmeida, H., Domingues, R. M., Mithieux, S. M., Pires, R. A., et. al.(2019). Tropoelastin-Coated Tendon Biomimetic Scaffolds Promote Stem Cell Tenogenic Commitment and Deposition of Elastin-Rich Matrix. ACS applied materials & interfaces, 11(22), 19830-19840por
dc.description.abstractTendon tissue engineering strategies that recreate the biophysical and biochemical native microenvironment have a greater potential to achieve regeneration. Here, we developed tendon biomimetic scaffolds using mechanically competent yarns of poly-ε-caprolactone, chitosan and cellulose nanocrystals to recreate the inherent tendon hierarchy from the nano to macro scale. These were then coated with tropoelastin (TROPO) through polydopamine linking (PDA), to mimic the native extracellular matrix (ECM) composition and elasticity. Both PDA and TROPO coatings decreased surface stiffness without masking the underlying substrate. We found that human adipose-derived stem cells (hASCs) seeded onto these TROPO biomimetic scaffolds more rapidly acquired their spindle-shape morphology and high aspect ratio characteristic of tenocytes. Immunocytochemistry shows that the PDA and TROPO-coated surfaces boosted differentiation of hASCs towards the tenogenic lineage, with sustained expression of the tendon-related markers scleraxis and tenomodulin up to 21 days of culture. Furthermore, these surfaces enabled the deposition of a tendon-like ECM, supported by the expression of collagens type I and III, tenascin and decorin. Gene expression analysis revealed a downregulation of osteogenic and fibrosis markers in the presence of TROPO when compared with the control groups, suggesting proper ECM deposition. Remarkably, differentiated cells exposed to TROPO acquired an elastogenic profile due to the evident elastin synthesis and deposition, contributing to the formation of a more mimetic matrix in comparison with the PDA-coated and uncoated conditions. In summary, our biomimetic substrates combining biophysical and biological cues modulate stem cell behavior potentiating their long-term tenogenic commitment and the production of an elastin-rich ECM.por
dc.description.sponsorshipEuropean Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 706996, Teaming grant agreement No 739572 – The Discoveries CTR, European Research Council grant agreement No 726178, and ERA Chair grant agreement No 668983 - FORECAST; Biomedical Engineering Australian Mobility (BEAM) Program – Master Joint Mobility Project between EU Commission Australian Government; Fundação para a Ciência e a Tecnologia (FCT) for Post-Doc grant SFRH/BPD/112459/2015 and project SmarTendon (PTDC/NAN-MAT/30595/2017); Norte Portugal Regional Operational Program (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund for NORTE-01-0145-FEDER-000021por
dc.subjectElastin de novo synthesispor
dc.subjectHierarchical scaffoldspor
dc.subjectHuman-adipose derived stem cellspor
dc.subjectTenogenic differentiationpor
dc.titleTropoelastin coated tendon biomimetic scaffolds promote stem cell tenogenic commitment and deposition of elastin-rich matrixpor
dc.subject.fosCiências Médicas::Biotecnologia Médicapor
dc.subject.wosScience & Technologypor
sdum.journalAcs Applied Materials & Interfacespor
Appears in Collections:3B’s - Artigos em revistas/Papers in scientific journals

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