Tecnologias para estudo e tratamento da insuficiência venosa crônica: desenvolvimento de microambientes e abordagens nanotecnológicas

Detalhes bibliográficos
Autor(a) principal: Menezes, Paula dos Passos
Data de Publicação: 2019
Tipo de documento: Tese
Idioma: por
Título da fonte: Repositório Institucional da UFS
Texto Completo: http://ri.ufs.br/jspui/handle/riufs/13054
Resumo: Venous insufficiency is a disease caused by valvular incompetence and is highly prevalent in Western countries, significantly burdening health systems. The most severe form of the disease consists of venous ulcers that are difficult to heal. In view of this, the main objective of this thesis was to develop biomaterials for the study and treatment of venous ulcers, through nanotechnological approaches and regenerative medicine. In order to do so, three-dimensional microenvironments (3D) were developed in order to investigate the response of stem cells to different mechanical properties of the extracellular matrix, as well as the expression of proteins released from nanoparticles containing messenger RNA (mRNA) in order to propose a model of pathology study. In addition, compression stockings containing nanoencapsulated hesperetin has been developed for the treatment of venous ulcers. In view of the above, 720 hydrogels of different mechanical properties (9 to 46 kPa) were printed as biomechanical platforms of the extracellular matrix. The response of stem cells to these matrices was directly related to stiffness of the microenvironment, without damage to cellular viability. In addition, stiffer matrices presented a greater expression of proteins, which contributes to new studies involving the biochemical factors present in the microenvironment of the venous disease. Compressive stockings containing nanoencapsulated hesperetin have been shown to be promising for the treatment of ulcers by controlled release of hesperetin from the textiles into the microenvironment of the lesions. These nanocapsules remained adhesive in the textile during five washes, which makes this biomaterial interesting to treat this disease, since it associates the effect of the compression to the hypotensive activity of the hesperetin in the vascular endothelium. In view of this, we present the case report of a patient with long unhealed venous ulcers for two years, with the therapies prescribed before the beginning of this study. After six months of treatment with these compressive stockings, the patient presented significant improvement in their quality of life, associated with the disappearance of pain associated with injury and excellent healing. In addition, a significant whitening of the perilesional area was observed due to reduction of melanin and erythema. The healing of the lesions also contributed to the reduction of the venous diameters of different segments of the saphenous vein. Together, these results contribute to the desired clinical outcomes in the treatment of venous ulcers and contribute to further studies with larger samples. This research therefore contributes to the emergence of new therapeutic options for a disease of such importance in the context of public health, which is an essential part of Health Policies and economic development.
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spelling Menezes, Paula dos PassosAraújo, Adriano Antunes de SouzaGuterres, Silvia Stanisçuaski2020-03-17T19:19:18Z2020-03-17T19:19:18Z2019-02-21MENEZES, Paula dos Passos. Tecnologias para estudo e tratamento da insuficiência venosa crônica: desenvolvimento de microambientes e abordagens nanotecnológicas. 2019. 156 f. Tese (Doutorado em Ciências da Saúde) - Universidade Federal de Sergipe, Aracaju, 2019.http://ri.ufs.br/jspui/handle/riufs/13054Venous insufficiency is a disease caused by valvular incompetence and is highly prevalent in Western countries, significantly burdening health systems. The most severe form of the disease consists of venous ulcers that are difficult to heal. In view of this, the main objective of this thesis was to develop biomaterials for the study and treatment of venous ulcers, through nanotechnological approaches and regenerative medicine. In order to do so, three-dimensional microenvironments (3D) were developed in order to investigate the response of stem cells to different mechanical properties of the extracellular matrix, as well as the expression of proteins released from nanoparticles containing messenger RNA (mRNA) in order to propose a model of pathology study. In addition, compression stockings containing nanoencapsulated hesperetin has been developed for the treatment of venous ulcers. In view of the above, 720 hydrogels of different mechanical properties (9 to 46 kPa) were printed as biomechanical platforms of the extracellular matrix. The response of stem cells to these matrices was directly related to stiffness of the microenvironment, without damage to cellular viability. In addition, stiffer matrices presented a greater expression of proteins, which contributes to new studies involving the biochemical factors present in the microenvironment of the venous disease. Compressive stockings containing nanoencapsulated hesperetin have been shown to be promising for the treatment of ulcers by controlled release of hesperetin from the textiles into the microenvironment of the lesions. These nanocapsules remained adhesive in the textile during five washes, which makes this biomaterial interesting to treat this disease, since it associates the effect of the compression to the hypotensive activity of the hesperetin in the vascular endothelium. In view of this, we present the case report of a patient with long unhealed venous ulcers for two years, with the therapies prescribed before the beginning of this study. After six months of treatment with these compressive stockings, the patient presented significant improvement in their quality of life, associated with the disappearance of pain associated with injury and excellent healing. In addition, a significant whitening of the perilesional area was observed due to reduction of melanin and erythema. The healing of the lesions also contributed to the reduction of the venous diameters of different segments of the saphenous vein. Together, these results contribute to the desired clinical outcomes in the treatment of venous ulcers and contribute to further studies with larger samples. This research therefore contributes to the emergence of new therapeutic options for a disease of such importance in the context of public health, which is an essential part of Health Policies and economic development.A insuficiência venosa é uma doença causada por incompetência valvular e é altamente prevalente em países ocidentais, onerando de forma significativa os sistemas de saúde. A forma mais grave da doença, consiste em úlceras venosas de difícil cicatrização. Diante disto, o principal objetivo desta tese consistiu em desenvolver biomateriais para o tratamento de úlceras venosas, através de abordagens nanotecnológicas e da medicina regenerativa. Para tanto, foram desenvolvidos microambientes tridimensionais (3D), a fim de investigar a resposta de células tronco a diferentes propriedades mecânicas da matriz extracelular, bem como a expresão de proteínas liberadas a partir de nanopartículas contendo RNA mensageiro (mRNA) na perspectiva de propor um modelo de estudo da patologia. Além disso, foram desenvolvidas meias de compressão contendo hesperetina nanoencapsulada para tratamento de úlceras venosas. Diante do exposto, foram impressos 720 hidrogéis de diferentes propriedades mecânicas (9 a 46 kPa), como plataformas biométicas da matriz extracelular. A resposta de células tronco a estas matrizes foi diretamente relacionada a rigidez do microambiente, sem danos a viabilidade celular (86 – 96%). Ademais, matrizes mais rígidas apresentaram uma maior expressão de proteínas, o que contribui para novos estudos envolvendo os fatores bioquímicos presentes no microambiente da doença venosa. As meias compressivas contendo hesperetina nanoencapsulada mostraram-se promissoras para o tratamento de úlceras, mediante liberação controlada de hesperetina a partir dos tecidos, para o microambiente das lesões. Estas nanocápsulas permaneceram adesivas no tecido durante cinco lavagens, o que torna este biomaterial interessante para tratar esta doença, uma vez que associa o efeito da compressão a atividade hipotensora da hesperetina no endotélio vascular. Diante disto, apresentamos o relato de caso de um paciente com úlceras venosas de longa extensão não cicatrizadas durante dois anos, com as terapias prescritas antes do início deste estudo. Após seis meses de tratamento com esta meia, o paciente apresentou melhora significativa na sua qualidade de vida, provavelmente associada ao desaparecimento das dores associadas a lesão e excelente cicatrização. Além disso, foi observada um importante clareamento da área perilesional devido a redução de melanina e eritema. A cicatrização das lesões contribuiu ainda para a redução dos diâmetros venosos de diferentes segmentos da veia safena. Juntos, estes resultados contribuem para os desfechos clínicos desejados no tratamento de úlceras venosas e para estudos posteriores com amostras maiores. A realização dessa pesquisa serve como base para o advento de novas opções terapêuticas para uma doença de tamanha importância no contexto da saúde pública, o que constitui parte essencial das Políticas de Saúde e desenvolvimento econômico.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESAracajuporBioimpressãoInsuficiência venosaHesperetinaMicroambiente celularNanotecnologiaÚlcera venosaBioprintingVenous insufficiencyHesperetinMicroenvironmentNanotechnologyVenous ulcerCIENCIAS DA SAUDETecnologias para estudo e tratamento da insuficiência venosa crônica: desenvolvimento de microambientes e abordagens nanotecnológicasTechnologies for study and treatment of chronic venous insufficiency: development of microenvironments and nanotechnological approachesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisPós-Graduação em Ciências da SaúdeUniversidade Federal de Sergipereponame:Repositório Institucional da UFSinstname:Universidade Federal de Sergipe (UFS)instacron:UFSinfo:eu-repo/semantics/openAccessTEXTPAULA_PASSOS_MENEZES.pdf.txtPAULA_PASSOS_MENEZES.pdf.txtExtracted texttext/plain266016https://ri.ufs.br/jspui/bitstream/riufs/13054/3/PAULA_PASSOS_MENEZES.pdf.txt97f7ff1c3e6ee64e81b9e2b0e2a1ce3eMD53THUMBNAILPAULA_PASSOS_MENEZES.pdf.jpgPAULA_PASSOS_MENEZES.pdf.jpgGenerated Thumbnailimage/jpeg1260https://ri.ufs.br/jspui/bitstream/riufs/13054/4/PAULA_PASSOS_MENEZES.pdf.jpg316f0262454a658b830344053277f18bMD54LICENSElicense.txtlicense.txttext/plain; charset=utf-81475https://ri.ufs.br/jspui/bitstream/riufs/13054/1/license.txt098cbbf65c2c15e1fb2e49c5d306a44cMD51ORIGINALPAULA_PASSOS_MENEZES.pdfPAULA_PASSOS_MENEZES.pdfapplication/pdf4404378https://ri.ufs.br/jspui/bitstream/riufs/13054/2/PAULA_PASSOS_MENEZES.pdf690b4953fbcc257c392bbd2bd11571a7MD52riufs/130542020-03-17 16:19:18.587oai:ufs.br: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Repositório InstitucionalPUBhttps://ri.ufs.br/oai/requestrepositorio@academico.ufs.bropendoar:2020-03-17T19:19:18Repositório Institucional da UFS - Universidade Federal de Sergipe (UFS)false
dc.title.pt_BR.fl_str_mv Tecnologias para estudo e tratamento da insuficiência venosa crônica: desenvolvimento de microambientes e abordagens nanotecnológicas
dc.title.alternative.eng.fl_str_mv Technologies for study and treatment of chronic venous insufficiency: development of microenvironments and nanotechnological approaches
title Tecnologias para estudo e tratamento da insuficiência venosa crônica: desenvolvimento de microambientes e abordagens nanotecnológicas
spellingShingle Tecnologias para estudo e tratamento da insuficiência venosa crônica: desenvolvimento de microambientes e abordagens nanotecnológicas
Menezes, Paula dos Passos
Bioimpressão
Insuficiência venosa
Hesperetina
Microambiente celular
Nanotecnologia
Úlcera venosa
Bioprinting
Venous insufficiency
Hesperetin
Microenvironment
Nanotechnology
Venous ulcer
CIENCIAS DA SAUDE
title_short Tecnologias para estudo e tratamento da insuficiência venosa crônica: desenvolvimento de microambientes e abordagens nanotecnológicas
title_full Tecnologias para estudo e tratamento da insuficiência venosa crônica: desenvolvimento de microambientes e abordagens nanotecnológicas
title_fullStr Tecnologias para estudo e tratamento da insuficiência venosa crônica: desenvolvimento de microambientes e abordagens nanotecnológicas
title_full_unstemmed Tecnologias para estudo e tratamento da insuficiência venosa crônica: desenvolvimento de microambientes e abordagens nanotecnológicas
title_sort Tecnologias para estudo e tratamento da insuficiência venosa crônica: desenvolvimento de microambientes e abordagens nanotecnológicas
author Menezes, Paula dos Passos
author_facet Menezes, Paula dos Passos
author_role author
dc.contributor.author.fl_str_mv Menezes, Paula dos Passos
dc.contributor.advisor1.fl_str_mv Araújo, Adriano Antunes de Souza
dc.contributor.advisor-co1.fl_str_mv Guterres, Silvia Stanisçuaski
contributor_str_mv Araújo, Adriano Antunes de Souza
Guterres, Silvia Stanisçuaski
dc.subject.por.fl_str_mv Bioimpressão
Insuficiência venosa
Hesperetina
Microambiente celular
Nanotecnologia
Úlcera venosa
topic Bioimpressão
Insuficiência venosa
Hesperetina
Microambiente celular
Nanotecnologia
Úlcera venosa
Bioprinting
Venous insufficiency
Hesperetin
Microenvironment
Nanotechnology
Venous ulcer
CIENCIAS DA SAUDE
dc.subject.eng.fl_str_mv Bioprinting
Venous insufficiency
Hesperetin
Microenvironment
Nanotechnology
Venous ulcer
dc.subject.cnpq.fl_str_mv CIENCIAS DA SAUDE
description Venous insufficiency is a disease caused by valvular incompetence and is highly prevalent in Western countries, significantly burdening health systems. The most severe form of the disease consists of venous ulcers that are difficult to heal. In view of this, the main objective of this thesis was to develop biomaterials for the study and treatment of venous ulcers, through nanotechnological approaches and regenerative medicine. In order to do so, three-dimensional microenvironments (3D) were developed in order to investigate the response of stem cells to different mechanical properties of the extracellular matrix, as well as the expression of proteins released from nanoparticles containing messenger RNA (mRNA) in order to propose a model of pathology study. In addition, compression stockings containing nanoencapsulated hesperetin has been developed for the treatment of venous ulcers. In view of the above, 720 hydrogels of different mechanical properties (9 to 46 kPa) were printed as biomechanical platforms of the extracellular matrix. The response of stem cells to these matrices was directly related to stiffness of the microenvironment, without damage to cellular viability. In addition, stiffer matrices presented a greater expression of proteins, which contributes to new studies involving the biochemical factors present in the microenvironment of the venous disease. Compressive stockings containing nanoencapsulated hesperetin have been shown to be promising for the treatment of ulcers by controlled release of hesperetin from the textiles into the microenvironment of the lesions. These nanocapsules remained adhesive in the textile during five washes, which makes this biomaterial interesting to treat this disease, since it associates the effect of the compression to the hypotensive activity of the hesperetin in the vascular endothelium. In view of this, we present the case report of a patient with long unhealed venous ulcers for two years, with the therapies prescribed before the beginning of this study. After six months of treatment with these compressive stockings, the patient presented significant improvement in their quality of life, associated with the disappearance of pain associated with injury and excellent healing. In addition, a significant whitening of the perilesional area was observed due to reduction of melanin and erythema. The healing of the lesions also contributed to the reduction of the venous diameters of different segments of the saphenous vein. Together, these results contribute to the desired clinical outcomes in the treatment of venous ulcers and contribute to further studies with larger samples. This research therefore contributes to the emergence of new therapeutic options for a disease of such importance in the context of public health, which is an essential part of Health Policies and economic development.
publishDate 2019
dc.date.issued.fl_str_mv 2019-02-21
dc.date.accessioned.fl_str_mv 2020-03-17T19:19:18Z
dc.date.available.fl_str_mv 2020-03-17T19:19:18Z
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dc.identifier.citation.fl_str_mv MENEZES, Paula dos Passos. Tecnologias para estudo e tratamento da insuficiência venosa crônica: desenvolvimento de microambientes e abordagens nanotecnológicas. 2019. 156 f. Tese (Doutorado em Ciências da Saúde) - Universidade Federal de Sergipe, Aracaju, 2019.
dc.identifier.uri.fl_str_mv http://ri.ufs.br/jspui/handle/riufs/13054
identifier_str_mv MENEZES, Paula dos Passos. Tecnologias para estudo e tratamento da insuficiência venosa crônica: desenvolvimento de microambientes e abordagens nanotecnológicas. 2019. 156 f. Tese (Doutorado em Ciências da Saúde) - Universidade Federal de Sergipe, Aracaju, 2019.
url http://ri.ufs.br/jspui/handle/riufs/13054
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