Micropatterned platelet lysate-based membranes for cell culture and cardiac regeneration

Detalhes bibliográficos
Autor(a) principal: Figueiredo, Samuel Garrido
Data de Publicação: 2021
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10773/32854
Resumo: Heart diseases are a major cause of dead worldwide. Myocardial infarction is one of the most serious problems, leading to the destruction of functional heart tissue and putting patients at constant risk of heart failure. Conventional pharmacologic therapies or organ transplantation are often not efficient and associated with multiple limitations, and therefore the search for other alternatives is a need. Tissue engineering (TE) has emerged as an alternative to produce structures that potentiate cardiac regeneration or microtissues development for in vitro drug screening. TE typically combines biomaterials, cells, and biochemical signals. The ideal 3D structure for a cardiac patch must combine several structural and functional properties that should match the existing in the native myocardium. Human methacryloyl platelet lysates (PLMA)-derived hydrogels have recently been reported as a human based biomaterial with tuneable mechanical properties that support human cell culture. In this thesis project, micropatterned PLMA-based hydrogels were developed. To do so, PLs were chemically modified with methacryloyl groups, thus becoming photocrosslinkable. Afterwards, polydimethylsiloxane (PDMS) was used to produce micropatterned structures with microwells to be used as counter molds. Two different micropillars patterns were made - hexagonal and square. Mechanical characterization shows that micropatterned PLMA hydrogels have mechanical properties dependent on the concentration of the polymer present in the precursor solution. Biological assays were performed in order to understand cells response to topography and results showed that PLMA-hydrogels support the adhesion and proliferation of both human umbilical vein endothelial cells (HUVECs) and myoblasts derived from embryonic myocardium rat tissue (H9c2(2-1)). In this work we were capable to produce micropatterned PLMA-hydrogels which have suitable biomechanical properties, allowing a good cell adhesion, proliferation, and pre-formation of a microtissue with potential crosstalk between cells at the scaffold.
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spelling Micropatterned platelet lysate-based membranes for cell culture and cardiac regenerationTissue engineeringCardiac patchesHydrogelsPLMAMicropillarsMicropatterned surfacesMicrofabricationHeart diseases are a major cause of dead worldwide. Myocardial infarction is one of the most serious problems, leading to the destruction of functional heart tissue and putting patients at constant risk of heart failure. Conventional pharmacologic therapies or organ transplantation are often not efficient and associated with multiple limitations, and therefore the search for other alternatives is a need. Tissue engineering (TE) has emerged as an alternative to produce structures that potentiate cardiac regeneration or microtissues development for in vitro drug screening. TE typically combines biomaterials, cells, and biochemical signals. The ideal 3D structure for a cardiac patch must combine several structural and functional properties that should match the existing in the native myocardium. Human methacryloyl platelet lysates (PLMA)-derived hydrogels have recently been reported as a human based biomaterial with tuneable mechanical properties that support human cell culture. In this thesis project, micropatterned PLMA-based hydrogels were developed. To do so, PLs were chemically modified with methacryloyl groups, thus becoming photocrosslinkable. Afterwards, polydimethylsiloxane (PDMS) was used to produce micropatterned structures with microwells to be used as counter molds. Two different micropillars patterns were made - hexagonal and square. Mechanical characterization shows that micropatterned PLMA hydrogels have mechanical properties dependent on the concentration of the polymer present in the precursor solution. Biological assays were performed in order to understand cells response to topography and results showed that PLMA-hydrogels support the adhesion and proliferation of both human umbilical vein endothelial cells (HUVECs) and myoblasts derived from embryonic myocardium rat tissue (H9c2(2-1)). In this work we were capable to produce micropatterned PLMA-hydrogels which have suitable biomechanical properties, allowing a good cell adhesion, proliferation, and pre-formation of a microtissue with potential crosstalk between cells at the scaffold.As doenças cardíacas são uma das principais causas de morte em todo o mundo. O enfarte do miocárdio é um dos problemas mais graves, levando à destruição de tecido cardíaco funcional e colocando os doentes em risco constante de insuficiência cardíaca. As terapias farmacológicas convencionais ou transplantes de órgãos não são muitas vezes eficientes e associadas a múltiplas limitações, pelo que a procura por outras alternativas é uma necessidade. A engenharia de tecidos surgiu como uma alternativa para produzir estruturas que potenciem a regeneração cardíaca ou o desenvolvimento de microtecidos para o teste de fármacos in vitro. A engenharia de tecidos combina tipicamente biomateriais, células e sinais bioquímicos. A estrutura 3D ideal para um patch cardíaco deve combinar várias propriedades estruturais e funcionais que devem corresponder às do miocárdio nativo. Os hidrogéis derivados de lisados de plaquetas humanas metacrilatados (PLMA) foram recentemente reportados como um biomaterial de base humana com propriedades mecânicas adaptáveis que suportam a cultura de células humanas. Neste projeto de tese, foram desenvolvidos hidrogéis micropadronizados à base de PLMA. Para tal, os PL foram quimicamente modificados com grupos metacrílicos, tornando-se assim foto reticuláveis. Posteriormente, o polidimetilsiloxano (PDMS) foi utilizado para produzir estruturas micropadronizadas com micropoços para serem utilizados como contra moldes. Foram feitos dois padrões diferentes de micropilares - hexagonais e quadrados - com uma estrutura bem definida. A caracterização mecânica demonstrou que os hidrogéis de PLMA micropadronizados têm propriedades mecânicas ajustáveis dependentes da concentração de polímero usado na solução precursora. Foram realizados ensaios biológicos para compreender a resposta das células à topografia e os resultados mostraram que os hidrogéis de PLMA suportam a adesão e proliferação tanto das células endoteliais da veia umbilical humana (HUVECs) como dos cardiomioblastos derivados do tecido embrionário do miocárdio de rato (H9c2(2-1)). Neste trabalho fomos capazes de produzir hidrogéis micropadronizados à base de PLMA com propriedades biomecânicas adequadas, permitindo uma boa adesão celular, proliferação e pré-formação de um microtecido com potencial comunicação entre células no scaffold.2023-12-14T00:00:00Z2021-12-10T00:00:00Z2021-12-10info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10773/32854engFigueiredo, Samuel Garridoinfo:eu-repo/semantics/embargoedAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-02-22T12:03:18Zoai:ria.ua.pt:10773/32854Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:04:24.868652Repositório 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 Micropatterned platelet lysate-based membranes for cell culture and cardiac regeneration
title Micropatterned platelet lysate-based membranes for cell culture and cardiac regeneration
spellingShingle Micropatterned platelet lysate-based membranes for cell culture and cardiac regeneration
Figueiredo, Samuel Garrido
Tissue engineering
Cardiac patches
Hydrogels
PLMA
Micropillars
Micropatterned surfaces
Microfabrication
title_short Micropatterned platelet lysate-based membranes for cell culture and cardiac regeneration
title_full Micropatterned platelet lysate-based membranes for cell culture and cardiac regeneration
title_fullStr Micropatterned platelet lysate-based membranes for cell culture and cardiac regeneration
title_full_unstemmed Micropatterned platelet lysate-based membranes for cell culture and cardiac regeneration
title_sort Micropatterned platelet lysate-based membranes for cell culture and cardiac regeneration
author Figueiredo, Samuel Garrido
author_facet Figueiredo, Samuel Garrido
author_role author
dc.contributor.author.fl_str_mv Figueiredo, Samuel Garrido
dc.subject.por.fl_str_mv Tissue engineering
Cardiac patches
Hydrogels
PLMA
Micropillars
Micropatterned surfaces
Microfabrication
topic Tissue engineering
Cardiac patches
Hydrogels
PLMA
Micropillars
Micropatterned surfaces
Microfabrication
description Heart diseases are a major cause of dead worldwide. Myocardial infarction is one of the most serious problems, leading to the destruction of functional heart tissue and putting patients at constant risk of heart failure. Conventional pharmacologic therapies or organ transplantation are often not efficient and associated with multiple limitations, and therefore the search for other alternatives is a need. Tissue engineering (TE) has emerged as an alternative to produce structures that potentiate cardiac regeneration or microtissues development for in vitro drug screening. TE typically combines biomaterials, cells, and biochemical signals. The ideal 3D structure for a cardiac patch must combine several structural and functional properties that should match the existing in the native myocardium. Human methacryloyl platelet lysates (PLMA)-derived hydrogels have recently been reported as a human based biomaterial with tuneable mechanical properties that support human cell culture. In this thesis project, micropatterned PLMA-based hydrogels were developed. To do so, PLs were chemically modified with methacryloyl groups, thus becoming photocrosslinkable. Afterwards, polydimethylsiloxane (PDMS) was used to produce micropatterned structures with microwells to be used as counter molds. Two different micropillars patterns were made - hexagonal and square. Mechanical characterization shows that micropatterned PLMA hydrogels have mechanical properties dependent on the concentration of the polymer present in the precursor solution. Biological assays were performed in order to understand cells response to topography and results showed that PLMA-hydrogels support the adhesion and proliferation of both human umbilical vein endothelial cells (HUVECs) and myoblasts derived from embryonic myocardium rat tissue (H9c2(2-1)). In this work we were capable to produce micropatterned PLMA-hydrogels which have suitable biomechanical properties, allowing a good cell adhesion, proliferation, and pre-formation of a microtissue with potential crosstalk between cells at the scaffold.
publishDate 2021
dc.date.none.fl_str_mv 2021-12-10T00:00:00Z
2021-12-10
2023-12-14T00:00:00Z
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