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Norbornene-chitosan nanoparticles with and without a conjugated VEGF-peptide an...

Alves, PM; Fonseca, DR; Bidarra, SJ; Gomes, A; Gomes, P; Barrias, CC; Martins, MCL

Impaired angiogenesis in skin chronic wounds prolongs inflammation and compromises wound healing. Several strategies have been attempted to improve vascularization, such as application of growth factors, like the vascular endothelial growth factor (VEGF). However, VEGF is expensive, has a short half-life in vivo and has been associated to tumorigenesis when used in high concentrations. QK peptide is a shorter (...


Enhancement of hMSC In Vitro Proliferation by Surface Immobilization of a Hepar...

Cimino, M; Parreira, P; Leiro, V; Sousa, A; Gonçalves, RM; Barrias, CC; Martins, MCL

The use of human Mesenchymal Stem Cells (hMSC) as therapeutic agents for advanced clinical therapies relies on their in vitro expansion. Over the last years, several efforts have been made to optimize hMSC culture protocols, namely by mimicking the cell physiological microenvironment, which strongly relies on signals provided by the extracellular matrix (ECM). ECM glycosaminoglycans, such as heparan-sulfate, se...


Engineering a Vascularized 3D Hybrid System to Model Tumor-Stroma Interactions ...

Teixeira, FC; Chaves, S; Torres, AL; Barrias, CC; Bidarra, SJ

The stromal microenvironment of breast tumors, namely the vasculature, has a key role in tumor development and metastatic spread. Tumor angiogenesis is a coordinated process, requiring the cooperation of cancer cells, stromal cells, such as fibroblasts and endothelial cells, secreted factors and the extracellular matrix (ECM). In vitro models capable of capturing such complex environment are still scarce, but a...


Engineering modular half-antibody conjugated nanoparticles for targeting CD44v6...

Lourenço, BN; Pereira, RF; Barrias, CC; Fischbach, C; Oliveira, C; Granja, PL

Gastric cancer (GC) remains a major cause of death worldwide mainly because of the late detection in advanced stage. Recently, we proposed CD44v6 as a relevant marker for early detection of GC, opening new avenues for GC-targeted theranostics. Here, we designed a modular nanoscale system that selectively targets CD44v6-expressing GC cells by the site-oriented conjugation of a new-engineered CD44v6 half-antibody...


Smart biomaterial-based systems for intrinsic stimuli-responsive chronic wound ...

Alves, PM; Barrias, CC; Gomes, P; Martins, MCL

Skin chronic wounds are associated with a state of persistent inflammation and often with infection, originating a specific microenvironment characterized by increased temperature, alkaline pH, elevated enzymatic activity, and high levels of reactive oxygen species (ROS). These alterations can be explored as intrinsic triggers in the design of stimuli-responsive biomaterials for the release of bioactive molecul...


Analysis of the effect of increased a2,3-sialylation on RTK activation in MKN45...

Balmaña, M; Diniz, F; Feijão, T; Barrias, CC; Mereiter, S; Reis, CA

In the scenario of personalized medicine, targeted therapies are currently the focus of cancer drug development. These drugs can block the growth and spread of tumor cells by interfering with key molecules involved in malignancy, such as receptor tyrosine kinases (RTKs). MET and Recepteur d’Origine Nantais (RON), which are RTKs frequently overactivated in gastric cancer, are glycoprotein receptors whose activat...


Development of an Improved 3D in vitro Intestinal Model to Perform Permeability...

Macedo, MH; Martínez, E; Barrias, CC; Sarmento, B

The small intestine is the primary site of drug absorption following oral administration, making paramount the proper monitoring of the absorption process. In vitro tools to predict intestinal absorption are particularly important in preclinical drug development since they are less laborious and cost-intensive and raise less ethical considerations compared to in vivo studies. The Caco-2 model is considered the ...


Glycosaminoglycan-inspired biomaterials for the development of bioactive hydrog...

Neves, MI; Araújo, M; Moroni, L; Silva, RMP; Barrias, CC

Glycosaminoglycans (GAG) are long, linear polysaccharides that display a wide range of relevant biological roles. Particularly, in the extracellular matrix (ECM) GAG specifically interact with other biological molecules, such as growth factors, protecting them from proteolysis or inhibiting factors. Additionally, ECM GAG are partially responsible for the mechanical stability of tissues due to their capacity to ...


Reshaping in vitro Models of Breast Tissue: Integration of Stromal and Parenchy...

Silva, PB; Coelho, M; Bidarra, SJ; Neves, SC; Barrias, CC

Breast tissue consists of an epithelial parenchyma embedded in stroma, of heterogeneous and complex composition, undergoing several morphological and functional alterations throughout females' lifespan. Improved knowledge on the crosstalk between parenchymal and stromal mammary cells should provide important insights on breast tissue dynamics, both under healthy and diseased states. Here, we describe an advance...


Modulating Alginate Hydrogels for Improved Biological Performance as Cellular 3...

Neves, MI; Moroni, L; Barrias, CC

The rational choice and design of biomaterials for biomedical applications is crucial for successful in vitro and in vivo strategies, ultimately dictating their performance and potential clinical applications. Alginate, a marine-derived polysaccharide obtained from seaweeds, is one of the most widely used polymers in the biomedical field, particularly to build three dimensional (3D) systems for in vitro culture...


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