Nanofibras de PHBV contendo vidros boratos bioativos modificados com íons terapêuticos para regeneração tecidual
Data
2023-07-13
Autores
Santos, Verônica Ribeiro 
Orientadores
Trichês, Eliandra de Sousa
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
A regeneração de tecidos crônicos requer curativos inteligentes, e os esforços da biomedicina têm se voltado à nanofibras poliméricas eletrofiadas contendo compostos bioativos para promover maior velocidade de recuperação e bem-estar à pacientes lesionados. O poli(3-hidroxibutirato-co-3-hidroxivalerato) (PHBV) é um polímero biocompatível e natural cujas propriedades intrínsecas garante sua eficácia como um curativo avançado, enquanto o vidro borato bioativo de composição 45B5 (46,1% B2O3, 26,9% CaO, 24,4% Na2O e 2,6% P2O5, % em mol) pode propiciar a bioatividade ausente neste polímero. Adicionalmete, os produtos de dissolução do 45B5 acionam processos celulares que auxiliam a cicatrização, e se incorporados com íons terapêuticos como Co2+, Cu2+ e Zn2+ podem ainda promover ação angiogênica e/ou antibacteriana. Neste sentido, o objetivo deste trabalho foi produzir nanofibras de PHBV contendo vidro borato bioativo 45B5 dopados com Co2+, Cu2+ e Zn2+ (45B5Co, 45B5Cu e 45B5Zn, respectivamente) para aplicações na regeneração do tecido cutâneo. Os vidros bioativos foram obtidos pela técnica de glicotremia; uma metodologia desenvolvida neste projeto de pesquisa a partir da capacidade de álcoois glicóis de realizarem reações de transesterificação com precursores de óxidos ácidos e alcóxicos organometálicos. Os vidros 45B5 dopados com Co2+, Cu2+ e Zn2+ revelaram possuir grande similaridade estrutural entre si, sendo formadas predominantemente por unidades metaborato tipo anel. O ensaio de bioatividade indicou precipitação de hidroxiapatita (Ca5(PO4)3(OH)) logo nas primeiras horas para todos os vidros, além de ausência de citotoxicidade quando expostas à queratinócitos humanos (HaCat) em concentrações inferiores a 0,5 mg/mL em 24 horas de exposição, enquanto o vidro 45B5Zn revelou a maior atividade antibacteriana contra S. aureus. Os vidros 45B5 incorporados com Co2+, Cu2+ e Zn2+ foram encapsulados à nanofibras de PHBV, levando a obtenção de compósitos de inferiores grau de cristalinidade, temperatura de decomposição e propriedades mecânicas. As nanofibras encapsuladas com 45B5 e 45B5Co revelaram elevada viabilidade celular após 3 e 7 dias de exposição à queratinócitos humanos, indicando a bioatividade das mesmas. A partir da execução deste trabalho, os vidros boratos bioativos produzidos possuem alto potencial de aplicação na engenharia de tecidos moles em materiais e dispositivos para cicatrização de feridas. Além disso, o método de glicotermia gerou novas perspectivas para a síntese de uma ampla gama de composições de vidros bioativos.
Chronic wounds require intelligent dressings, and biomedicine has relied on electrospun polymeric nanofibers containing bioactive compounds to promote greater speed of recovery and well-being to injured patients. Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) is a biocompatible and natural polymer whose intrinsic properties guarantee its effectiveness as an advanced dressing, while the bioactive borate glass of composition 45B5 (46.1% B2O3, 26, 9% CaO, 24.4% Na2O and 2.6% P2O5, % in mol) can provide the bioactivity absent in this polymer. Additionally, 45B5 dissolution products trigger cellular processes that aid healing, and if incorporated with therapeutic ions such as Co2+, Cu2+ and Zn2+ may even promote angiogenic and/or antibacterial action. In this sense, the aim of this work was to produce PHBV nanofibers containing bioactive borate glass 45B5 doped with Co2+, Cu2+ and Zn2+ (45B5Co, 45B5Cu and 45B5Zn, respectively) for applications in skin tissue regeneration. The bioactive glasses wer obtained by the glycolthermal method, a technique developed in this research project based on the ability of glycol alcohols to carry out transesterification reactions with acidic and organometallic alkoxides oxide precursors. The 45B5 glasses doped with Co2+, Cu2+, and Zn2+ revealed to have great structural similarity was verified between all compositions; being formed predominantly by ring-type metaborate. The bioactivity assay indicated precipitation of hydroxyapatite (Ca5(PO4)3(OH)) in the first hours for all glasses, in addition to the absence of cytotoxicity when exposed to human keratinocytes (HaCat) at concentrations below 0.5 mg/mL in 24 hours of exposure. Furthermore, the 45B5Zn glass showed the highest antibacterial activity against S. aureus. The produced glasses were encapsulated in PHBV nanofibers, leading to composites with lower degrees of crystallinity, decomposition temperature and mechanical properties. Nanofibers encapsulated with 45B5 and 45B5Co showed high cell viability after 3 and 7 days of exposure to human keratinocytes, indicating their bioactivity. From the execution of this research, the bioactive borate glasses produced have a high potential for application in soft tissue engineering materials and devices for wound healing. In addition, the glycolthermal method has generated new perspectives for the synthesis of a wide range of bioactive glass compositions and their application in tissue engineering.
Chronic wounds require intelligent dressings, and biomedicine has relied on electrospun polymeric nanofibers containing bioactive compounds to promote greater speed of recovery and well-being to injured patients. Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) is a biocompatible and natural polymer whose intrinsic properties guarantee its effectiveness as an advanced dressing, while the bioactive borate glass of composition 45B5 (46.1% B2O3, 26, 9% CaO, 24.4% Na2O and 2.6% P2O5, % in mol) can provide the bioactivity absent in this polymer. Additionally, 45B5 dissolution products trigger cellular processes that aid healing, and if incorporated with therapeutic ions such as Co2+, Cu2+ and Zn2+ may even promote angiogenic and/or antibacterial action. In this sense, the aim of this work was to produce PHBV nanofibers containing bioactive borate glass 45B5 doped with Co2+, Cu2+ and Zn2+ (45B5Co, 45B5Cu and 45B5Zn, respectively) for applications in skin tissue regeneration. The bioactive glasses wer obtained by the glycolthermal method, a technique developed in this research project based on the ability of glycol alcohols to carry out transesterification reactions with acidic and organometallic alkoxides oxide precursors. The 45B5 glasses doped with Co2+, Cu2+, and Zn2+ revealed to have great structural similarity was verified between all compositions; being formed predominantly by ring-type metaborate. The bioactivity assay indicated precipitation of hydroxyapatite (Ca5(PO4)3(OH)) in the first hours for all glasses, in addition to the absence of cytotoxicity when exposed to human keratinocytes (HaCat) at concentrations below 0.5 mg/mL in 24 hours of exposure. Furthermore, the 45B5Zn glass showed the highest antibacterial activity against S. aureus. The produced glasses were encapsulated in PHBV nanofibers, leading to composites with lower degrees of crystallinity, decomposition temperature and mechanical properties. Nanofibers encapsulated with 45B5 and 45B5Co showed high cell viability after 3 and 7 days of exposure to human keratinocytes, indicating their bioactivity. From the execution of this research, the bioactive borate glasses produced have a high potential for application in soft tissue engineering materials and devices for wound healing. In addition, the glycolthermal method has generated new perspectives for the synthesis of a wide range of bioactive glass compositions and their application in tissue engineering.
Descrição
Citação
Santos, V. R. Nanofibras de PHBV contendo vidros boratos bioativos modificados com íons terapêuticos para regeneração tecidual. São José dos Campos, 2023. 129 p. Tese (Doutorado em Engenharia e Ciências de Materiais) - Universidade Federal de São Paulo.