Amphiphilic beads as depots for sustained drug release integrated into fibrillar scaffolds

Detalhes bibliográficos
Autor(a) principal: Gaharwar, Akhilesh K.
Data de Publicação: 2014
Outros Autores: Mihaila, Silvia M., Kulkarni, A. A., Patel, A., Luca, A. Di, Reis, R. L., Gomes, Manuela E., Blitterswijk, C. A. van, Moroni, L., Khademhosseini, Ali
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/1822/30359
Resumo: Native extracellular matrix (ECM) is a complex fibrous structure loaded with bioactive cues that affects the surrounding cells. A promising strategy to mimicking native tissue architecture for tissue engineering applications is to engineer fibrous scaffolds using electrospinning. By loading appropriate bioactive cues within these fibrous scaffolds, various cellular functions such as cell adhesion, proliferation and differentiation can be regulated. Here, we report on the encapsulation and sustained release of a model hydrophobic drug (dexamethasone (Dex)) within beaded fibrillar scaffold of poly(ethylene oxide terephthalate)-poly(butylene terephthalate) (PEOT/PBT), a polyether-ester multiblock copolymer to direct differentiation of human mesenchymal stem cells (hMSCs). The amphiphilic beads act as depots for sustained drug release that is integrated into the fibrillar scaffolds. The entrapment of Dex within the beaded structure results in sustained release of the drug over the period of 28days. This is mainly attributed to the diffusion driven release of Dex from the amphiphilic electrospun scaffolds. In vitro results indicate that hMSCs cultured on Dex containing beaded fibrillar scaffolds exhibit an increase in osteogenic differentiation potential, as evidenced by increased alkaline phosphatase (ALP) activity, compared to the direct infusion of Dex in the culture medium. The formation of a mineralized matrix is also significantly enhanced due to the controlled Dex release from the fibrous scaffolds. This approach can be used to engineer scaffolds with appropriate chemical cues to direct tissue regeneration
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spelling Amphiphilic beads as depots for sustained drug release integrated into fibrillar scaffoldsAmphiphilic polymerDrug releaseElectrospinningFibrous scaffoldsHuman mesenchymal stem cellsScience & TechnologyNative extracellular matrix (ECM) is a complex fibrous structure loaded with bioactive cues that affects the surrounding cells. A promising strategy to mimicking native tissue architecture for tissue engineering applications is to engineer fibrous scaffolds using electrospinning. By loading appropriate bioactive cues within these fibrous scaffolds, various cellular functions such as cell adhesion, proliferation and differentiation can be regulated. Here, we report on the encapsulation and sustained release of a model hydrophobic drug (dexamethasone (Dex)) within beaded fibrillar scaffold of poly(ethylene oxide terephthalate)-poly(butylene terephthalate) (PEOT/PBT), a polyether-ester multiblock copolymer to direct differentiation of human mesenchymal stem cells (hMSCs). The amphiphilic beads act as depots for sustained drug release that is integrated into the fibrillar scaffolds. The entrapment of Dex within the beaded structure results in sustained release of the drug over the period of 28days. This is mainly attributed to the diffusion driven release of Dex from the amphiphilic electrospun scaffolds. In vitro results indicate that hMSCs cultured on Dex containing beaded fibrillar scaffolds exhibit an increase in osteogenic differentiation potential, as evidenced by increased alkaline phosphatase (ALP) activity, compared to the direct infusion of Dex in the culture medium. The formation of a mineralized matrix is also significantly enhanced due to the controlled Dex release from the fibrous scaffolds. This approach can be used to engineer scaffolds with appropriate chemical cues to direct tissue regenerationAKG, SMM, LM and AK conceived the idea and designed the experiments. AKG and SMM fabricated electrospun scaffolds and performed the structural (SEM, FTIR), mechanical, and in vitro studies. AAK and AKGperformedDex release study. AKGand AP performed thermal analysis. AKG analyzed experimental data. AKG, SMM, LMand AK wrote the manuscript. ADL and CvB provided the polymers and corrected the manuscript. AKK, AP, MG and RLR revised the paper. All authors discussed the results and commented on the manuscript. Authors would like to thank Shilpaa Mukundan, Poornima Kulkarni and Dr. Arghya Paul for help with image analysis, drug release modeling and technical discussion respectively. AKG would like to thank Prof. Robert Langer for access to equipment and acknowledge financial support from MIT Portugal Program (MPP-09Call-Langer-47). SMMthanks the Portuguese Foundation for Science and Technology (FCT) for the personal grant SFRH/BD/42968/2008 (MIT-Portugal Program). This research was funded by the office of Naval Research Young National Investigator Award (AK), the Presidential Early Career Award for Scientists and Engineers (PECASE) (AK), the NIH (EB009196; DE019024; EB007249; HL099073; AR057837), the National Science Foundation CAREER award (DMR 0847287; AK), and the Dutch Technology Foundation (STW # 11135; LM, CvB, and AD).ElsevierUniversidade do MinhoGaharwar, Akhilesh K.Mihaila, Silvia M.Kulkarni, A. A.Patel, A.Luca, A. DiReis, R. L.Gomes, Manuela E.Blitterswijk, C. A. vanMoroni, L.Khademhosseini, Ali2014-042014-04-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/30359eng0168-365910.1016/j.jconrel.2014.04.03524794894http://www.ncbi.nlm.nih.gov/pubmed/24794894info: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:RCAAP2023-07-21T12:40:25Zoai:repositorium.sdum.uminho.pt:1822/30359Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:37:13.054256Repositório 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 Amphiphilic beads as depots for sustained drug release integrated into fibrillar scaffolds
title Amphiphilic beads as depots for sustained drug release integrated into fibrillar scaffolds
spellingShingle Amphiphilic beads as depots for sustained drug release integrated into fibrillar scaffolds
Gaharwar, Akhilesh K.
Amphiphilic polymer
Drug release
Electrospinning
Fibrous scaffolds
Human mesenchymal stem cells
Science & Technology
title_short Amphiphilic beads as depots for sustained drug release integrated into fibrillar scaffolds
title_full Amphiphilic beads as depots for sustained drug release integrated into fibrillar scaffolds
title_fullStr Amphiphilic beads as depots for sustained drug release integrated into fibrillar scaffolds
title_full_unstemmed Amphiphilic beads as depots for sustained drug release integrated into fibrillar scaffolds
title_sort Amphiphilic beads as depots for sustained drug release integrated into fibrillar scaffolds
author Gaharwar, Akhilesh K.
author_facet Gaharwar, Akhilesh K.
Mihaila, Silvia M.
Kulkarni, A. A.
Patel, A.
Luca, A. Di
Reis, R. L.
Gomes, Manuela E.
Blitterswijk, C. A. van
Moroni, L.
Khademhosseini, Ali
author_role author
author2 Mihaila, Silvia M.
Kulkarni, A. A.
Patel, A.
Luca, A. Di
Reis, R. L.
Gomes, Manuela E.
Blitterswijk, C. A. van
Moroni, L.
Khademhosseini, Ali
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade do Minho
dc.contributor.author.fl_str_mv Gaharwar, Akhilesh K.
Mihaila, Silvia M.
Kulkarni, A. A.
Patel, A.
Luca, A. Di
Reis, R. L.
Gomes, Manuela E.
Blitterswijk, C. A. van
Moroni, L.
Khademhosseini, Ali
dc.subject.por.fl_str_mv Amphiphilic polymer
Drug release
Electrospinning
Fibrous scaffolds
Human mesenchymal stem cells
Science & Technology
topic Amphiphilic polymer
Drug release
Electrospinning
Fibrous scaffolds
Human mesenchymal stem cells
Science & Technology
description Native extracellular matrix (ECM) is a complex fibrous structure loaded with bioactive cues that affects the surrounding cells. A promising strategy to mimicking native tissue architecture for tissue engineering applications is to engineer fibrous scaffolds using electrospinning. By loading appropriate bioactive cues within these fibrous scaffolds, various cellular functions such as cell adhesion, proliferation and differentiation can be regulated. Here, we report on the encapsulation and sustained release of a model hydrophobic drug (dexamethasone (Dex)) within beaded fibrillar scaffold of poly(ethylene oxide terephthalate)-poly(butylene terephthalate) (PEOT/PBT), a polyether-ester multiblock copolymer to direct differentiation of human mesenchymal stem cells (hMSCs). The amphiphilic beads act as depots for sustained drug release that is integrated into the fibrillar scaffolds. The entrapment of Dex within the beaded structure results in sustained release of the drug over the period of 28days. This is mainly attributed to the diffusion driven release of Dex from the amphiphilic electrospun scaffolds. In vitro results indicate that hMSCs cultured on Dex containing beaded fibrillar scaffolds exhibit an increase in osteogenic differentiation potential, as evidenced by increased alkaline phosphatase (ALP) activity, compared to the direct infusion of Dex in the culture medium. The formation of a mineralized matrix is also significantly enhanced due to the controlled Dex release from the fibrous scaffolds. This approach can be used to engineer scaffolds with appropriate chemical cues to direct tissue regeneration
publishDate 2014
dc.date.none.fl_str_mv 2014-04
2014-04-01T00:00:00Z
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/1822/30359
url http://hdl.handle.net/1822/30359
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 0168-3659
10.1016/j.jconrel.2014.04.035
24794894
http://www.ncbi.nlm.nih.gov/pubmed/24794894
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 Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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