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Engineering graphene-based electrodes for optical neural stimulation

Rodrigues, Artur Filipe; Tavares, Ana P. M.; Simões, Susana; Silva, Rui P. F. F.; Sobrino, Tomás; Figueiredo, Bruno R.; Sales, Goreti; Ferreira, Lino

Graphene-based materials (GBM) have been investigated in recent years with the aim of developing flexible interfaces to address a range of neurological disorders, where electrical stimulation may improve brain function and tissue regeneration. The recent discovery that GBM electrodes can generate an electrical response upon light exposure has inspired the development of non-genetic approaches capable of selecti...


Extracellular vesicles enriched with an endothelial cell pro-survival microRNA ...

Fernandes, Hugo; Zonnari, Alessandra; Abreu, Ricardo Cerqueira de; Aday, Sezin; Barão, Marta; Albino, Inês; Lino, Miguel; Branco, Ana; Seabra, Cátia

Endothelial cell (EC) activity is essential for tissue regeneration in several (patho)physiological contexts. However, our capacity to deliver in vivo biomolecules capable of controlling EC fate is relatively limited. Here, we screened a library of microRNA (miR) mimics and identified 25 miRs capable of enhancing the survival of ECs exposed to ischemia-mimicking conditions. In vitro, we showed that miR-425-5p, ...


Efficient spatially targeted gene editing using a near-infrared activatable pro...

Rebelo, Catarina; Reis, Tiago; Guedes, Joana; Saraiva, Cláudia; Rodrigues, Artur Filipe; Simões, Susana; Bernardino, Liliana; Peça, João

Spatial control of gene expression is critical to modulate cellular functions and deconstruct the function of individual genes in biological processes. Light-responsive gene-editing formulations have been recently developed; however, they have shown limited applicability in vivo due to poor tissue penetration, limited cellular transfection and the difficulty in evaluating the activity of the edited cells. Here,...


Induced pluripotent stem cell-derived vascular networks to screen nano-bio inte...

Estronca, Luís; Francisco, Vitor; Pitrez, Patrícia; Honório, Inês; Carvalho, Lara; Vazão, Helena; Blersh, Josephine; Rai, Akhilesh; Nissan, Xavier

This work was funded by FEDER through the Program COMPETE and by Portuguese fund through FCT in context of the projects PTDC/SAU-TOX/121887/2010, POCI-01-0145-FEDER-029229, POCI-01-0145-FEDER-016390 and POCI-01-0145-FEDER-029414, as well as the European project ERAatUC (ref. 669088). PRP wishes to thank FCT for a BD fellowship (SFRH/BD/71042/2010). The iMM Fish Facility was supported by CONGENTO LISBOA-01-0145-...


Therapeutic Nanoparticles for the Different Phases of Ischemic Stroke

Bernardo-Castro, Sara; Albino, Inês; Barrera-Sandoval, Ángela María; Tomatis, Francesca; Sousa, João André; Martins, Emanuel; Simões, Susana

Stroke represents the second leading cause of mortality and morbidity worldwide. Ischemic strokes are the most prevalent type of stroke, and they are characterized by a series of pathological events prompted by an arterial occlusion that leads to a heterogeneous pathophysiological response through different hemodynamic phases, namely the hyperacute, acute, subacute, and chronic phases. Stroke treatment is highl...


Interindividual heterogeneity affects the outcome of human cardiac tissue decel...

Tenreiro, Miguel F; Almeida, Henrique V.; Calmeiro, Tomás; Fortunato, Elvira; Ferreira, Lino; Alves, Paula M; Serra, Margarida

The extracellular matrix (ECM) of engineered human cardiac tissues corresponds to simplistic biomaterials that allow tissue assembly, or animal derived off-the-shelf non-cardiac specific matrices. Decellularized ECM from human cardiac tissue could provide a means to improve the mimicry of engineered human cardiac tissues. Decellularization of cardiac tissue samples using immersion-based methods can produce acce...


Exogenous loading of miRNAs into small extracellular vesicles

Abreu, Ricardo C de; Ramos, Cristiana V; Becher, Clarissa; Lino, Miguel; Jesus, Carlos; Martins, Paula A da Costa; Martins, Patrícia A T

Small extracellular vesicles (sEVs), through their natural ability to interact with biological membranes and exploit endogenous processing pathways to convey biological information, are quintessential for the delivery of therapeutically relevant compounds, such as microRNAs (miRNAs) and proteins. Here, we used a fluorescently-labelled miRNA to quantify the efficiency of different methods to modulate the cargo o...


High-throughput screening of nanoparticles in drug delivery

Tomé, Inês; Francisco, Vitor; Fernandes, Hugo; Ferreira, Lino

The use of pharmacologically active compounds to manage and treat diseases is of utmost relevance in clinical practice. It is well recognized that spatial-temporal control over the delivery of these biomolecules will greatly impact their pharmacokinetic profile and ultimately their therapeutic effect. Nanoparticles (NPs) prepared from different materials have been tested successfully in the clinic for the deliv...


Engineered extracellular vesicles as brain therapeutics

Lino, Miguel M.; Simões, Susana; Tomatis, Francesca; Albino, Inês; Barrera, Angela; Vivien, Denis; Sobrino, Tomás; Ferreira, Lino

Extracellular vesicles (EVs) are communication channels between different cell types in the brain, between the brain and the periphery and vice-versa, playing a fundamental role in physiology and pathology. The evidence that EVs might be able to cross the blood-brain barrier (BBB) make them very promising candidates as nanocarriers to treat brain pathologies. EVs contain a cocktail of bioactive factors, yet the...


Re-Use of Caco-2 Monolayers in Permeability Assays—Validation Regarding Cell Mo...

Pires, Cristiana L.; Praça, Catarina; Martins, Patrícia A. T.; Batista de Carvalho, Ana L. M.; Ferreira, Lino; Catarro, Maria Paula M. Marques

Caco-2 monolayers are a common in vitro model used to evaluate human intestinal absorption. The reference protocol requires 21 days post-seeding to establish a stable and confluent cell monolayer, which is used in a single permeability assay during the period of monolayer stability (up to day 30). In this work, we characterize variations in the tightness of the cell monolayer over the stable time interval and e...


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