RESUMO
A key strategy in enhancing the efficacy of collagen-based hydrogels involves incorporating polysaccharides, which have shown great promise for wound healing. In this study, semi-interpenetrating polymeric network (semi-IPN) hydrogels comprised of collagen (Col) with the macrocyclic oligosaccharide ß-cyclodextrin (ß-CD) (20-80 wt.%) were synthesised. Fourier-transform infrared (FTIR) spectroscopy confirmed the successful fabrication of these Col/ß-CD hydrogels, evidenced by the presence of characteristic absorption bands, including the urea bond band at â¼1740 cm-1, related with collagen crosslinking. Higher ß-CD content was associated with increased crosslinking, higher swelling, and faster gelation. The ß-CD content directly influenced the morphology and semi-crystallinity. All Col/ß-CD hydrogels displayed superabsorbent properties, enhanced thermal stability, and exhibited slow degradation rates. Mechanical properties were significantly improved with contents higher than ß-CD 40 wt.%. These hydrogels inhibited the growth of Escherichia coli bacteria and facilitated the controlled release of agents, such as malachite green, methylene blue, and ketorolac. The chemical composition of the Col/ß-CD hydrogels did not induce cytotoxic effects on monocytes and fibroblast cells. Instead, they actively promoted cellular metabolic activity, encouraging cell growth and proliferation. Moreover, cell signalling modulation was observed, leading to changes in the expression of TNF-α and IL-10 cytokines. In summary, the results of this research indicate that these novel hydrogels possess multifunctional characteristics, including biocompatibility, super-swelling capacity, good thermal, hydrolytic, and enzymatic degradation resistance, antibacterial activity, inflammation modulation, and the ability to be used for controlled delivery of therapeutic agents, indicating high potential for application in advanced wound dressings.
Assuntos
Antibacterianos , Bandagens , Colágeno , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Escherichia coli , Hidrogéis , beta-Ciclodextrinas , Hidrogéis/química , Hidrogéis/farmacologia , beta-Ciclodextrinas/química , Antibacterianos/farmacologia , Antibacterianos/química , Preparações de Ação Retardada/química , Colágeno/química , Escherichia coli/efeitos dos fármacos , Humanos , Cicatrização/efeitos dos fármacos , Inflamação/tratamento farmacológico , Animais , CamundongosRESUMO
OBJECTIVES: This study aimed to develop and evaluate resin-based antibacterial materials incorporating carvone for restorative dentistry. The objectives included assessing antimicrobial activity, conversion degree, mechanical properties, hydrolytic and hygroscopic behavior, cytotoxicity, among others. METHODOLOGY: Carvone was incorporated into resin-based materials following established protocols. Antimicrobial activity was evaluated against S. Aureus. Conversion degree, polimerization kinetics, mechanical properties, hydrolytic and hygroscopic behavior, cytotoxicity, and other properties were assessed using standardized tests and methodologies. RESULTS: Carvone-incorporated materials demonstrated significant antimicrobial activity, minimal changes in conversion degree, comparable mechanical properties, improved hydrolytic and hygroscopic behavior, and lack of cytotoxicity. Antimicrobial resins were obtained due to the hydrophobic nature of carvone and its ability to diffuse through the cell walls of microorganisms, causing membrane damage. The polymerization process yielded successful conversion, ensuring adequate material performance. SIGNIFICANCE: This study showcases that incorporating carvone into methacrylate-based resins can confer antimicrobial properties while preserving key material attributes. Antimicrobial activity against S. aureus is achieved without cytotoxicity in human fibroblasts. While flexural properties are affected only at carvone concentrations exceeding 9%, conversion degree and polymerization kinetics remain stable, except for a specific experimental formulation. These findings highlight the balanced integration of carvone. However, further work, including assessing antimicrobial performance against specific strains like S. Mutans and/or C. Albicans, and evaluating long-term effectiveness, is essential to establish the potential of these materials for dental restorations.
Assuntos
Resinas Compostas , Staphylococcus aureus , Humanos , Resinas Compostas/química , Teste de Materiais , Metacrilatos/química , Antibacterianos/farmacologia , Antibacterianos/química , Polímeros , Materiais DentáriosRESUMO
In this work, hydrogels based on semi-interpenetrating polymeric networks (semi-IPN) based on collagen-polyurethane-alginate were studied physicochemically and from different approaches for biomedical application. It was determined that the matrices in the hydrogel state are crosslinked by the formation of urea and amide bonds between the biopolymer chains and the polyurethane crosslinker. The increment in alginate content (0-40 wt%) significantly increases the swelling capacity, generating semi-crystalline granular structures with improved storage modulus and resistance to thermal, hydrolytic, and proteolytic degradation. The in vitro bioactivity results indicated that the composition of these novel hydrogels stimulates the metabolic activity of monocytes and fibroblasts, benefiting their proliferation; while in cancer cell lines, it was determined that the composition of these biomaterials decreases the metabolic activity of breast cancer cells after 48 h of stimulation, and for colon cancer cells their metabolic activity decreases after 72 h of contact for the hydrogel with 40 wt% alginate. The matrices show a behavior of multidose release of ketorolac, and a higher concentration of analgesic is released in the semi-IPN matrix. The inhibition capacity of Escherichia coli is higher if the polysaccharide concentration is low (10 wt%). The in vitro wound closure test (scratch test) results indicate that the hydrogel with 20 wt% alginate shows an improvement in wound closure at 15 days of contact. Finally, the bioactivity of mineralization was evaluated to demonstrate that these hydrogels can induce the formation of carbonated apatite on their surface. The engineered hydrogels show biomedical multifunctionality and they could be applied in soft and hard tissue healing strategies, anticancer therapies, and drug release devices.
Assuntos
Alginatos , Hidrogéis , Hidrogéis/química , Alginatos/química , Poliuretanos , Sistemas de Liberação de Medicamentos , Colágeno , Polímeros/químicaRESUMO
Aberrant expression of CD43 in malignant tumors of nonhematopoietic origin such as those from lung, cervix, colon, and breast has been shown to correlate with poor prognosis, providing tumor cells with enhanced motility, anchorage-independent growth, and in vivo tumor size, while protecting the cells of NK lysis and apoptosis. To further characterize the role of CD43 in cell transformation, we tested whether interfering its expression modified the capacity of the A549 non-small cell lung cancer cells to secrete molecules contributing to malignancy. The proteomic analysis of the secretome of serum-starved A549 cells revealed that cells expressing normal levels of CD43 released significantly high levels of molecules involved in extracellular matrix organization, angiogenesis, platelet degranulation, collagen degradation, and inflammation, as compared to CD43 RNAi cells. This data reveals a novel and unexpected role for CD43 in lung cancer development, mainly in remodeling the tumor microenvironment.
Assuntos
Matriz Extracelular/metabolismo , Leucossialina/metabolismo , Neoplasias Pulmonares/irrigação sanguínea , Neoplasias Pulmonares/metabolismo , Neovascularização Patológica/metabolismo , Células A549 , Inativação Gênica , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , NF-kappa B/metabolismo , Fator de Transcrição STAT3/metabolismo , Microambiente TumoralRESUMO
Basement membrane (BM) is a complex network of interacting proteins, including type IV collagen (Col IV) that acts as a scaffold that stabilizes the physical structures of tissues and regulates cellular processes. In the mammary gland, BM is a continuous deposit that separates epithelial cells from stroma, and its degradation is related with an increased potential for invasion and metastasis. Epithelial to mesenchymal transition (EMT) is a process by which epithelial cells are transdifferentiated to one mesenchymal state, and is a normal process during embryonic development, tissue remodeling and wound healing, as well as it has been implicated during cancer progression. In breast cancer cells, native Col IV induces migration and gelatinases secretion. However, the role of native Col IV on the EMT process in human mammary epithelial cells remains to be investigated. In the present study, we demonstrate that native Col IV induces down-regulation of E-cadherin expression, accompanied with an increase of Snail1, Snail2 and Sip1 transcripts. Native Col IV also induces an increase in N-cadherin and vimentin expression, an increase of MMP-2 secretion, the activation of FAK and NFκB, cell migration and invasion in MCF10A cells. In summary, these findings demonstrate, for the first time, that native Col IV induces an EMT-like process in MCF10A human mammary non-tumorigenic epithelial cells.
Assuntos
Colágeno Tipo IV/fisiologia , Células Epiteliais/fisiologia , Transição Epitelial-Mesenquimal , Glândulas Mamárias Humanas/citologia , Antígenos CD/genética , Antígenos CD/metabolismo , Caderinas/genética , Caderinas/metabolismo , Linhagem Celular , Movimento Celular , Receptor com Domínio Discoidina 1 , Ativação Enzimática , Células Epiteliais/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Quinase 1 de Adesão Focal/metabolismo , Expressão Gênica , Regulação da Expressão Gênica , Humanos , Metaloproteinase 2 da Matriz/metabolismo , NF-kappa B/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Fosforilação , Processamento de Proteína Pós-Traducional , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Fatores de Transcrição da Família Snail , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Regulação para Cima , Vimentina/genética , Vimentina/metabolismoRESUMO
Epidemiological studies and animal models suggest an association between high levels of dietary fat intake and an increased risk of developing breast cancer. Epithelial-mesenchymal-transition (EMT) is a process, by which epithelial cells are transdifferentiated to a mesenchymal state, and it has been implicated in cancer progression, including invasion and metastasis. Linoleic acid (LA) induces proliferation and invasion in breast cancer cells. However, the role of LA on the EMT process in human mammary epithelial cells remains to be studied. In the present study, we demonstrate that LA induces a transient down-regulation of E-cadherin expression, accompanied with an increase of Snail1, Snail2, Twist1, Twist2 and Sip1 expressions. Furthermore, LA induces FAK and NFκB activation, MMP-2 and -9 secretions, migration and invasion. In summary, our findings demonstrate, for the first time, that LA promotes an EMT-like process in MCF10A human mammary epithelial cells.