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Close-to-native bone repair via tissue-engineered endochondral ossification app...

Nadine, Sara; Fernandes, Inês J.; Correia, Clara R.; Mano, João F.

In order to solve the clinical challenges related to bone grafting, several tissue engineering (TE) strategies have been proposed to repair critical-sized defects. Generally, the classical TE approaches are designed to promote bone repair via intramembranous ossification. Although promising, strategies that direct the osteogenic differentiation of mesenchymal stem/stromal cells are usually characterized by a la...


Engineering immunomodulatory hydrogels and cell-laden systems towards bone rege...

Nadine, Sara; Correia, Clara R.; Mano, João F.

The well-known synergetic interplay between the skeletal and immune systems has changed the design of advanced bone tissue engineering strategies. The immune system is essential during the bone lifetime, with macrophages playing multiple roles in bone healing and biomaterial integration. If in the past, the most valuable aspect of implants was to avoid immune responses of the host, nowadays, it is well-establis...


Bioengineering the human bone marrow microenvironment in liquefied compartments...

Oliveira, Cláudia S.; Nadine, Sara; Gomes, Maria C.; Correia, Clara R.; Mano, João F.

Recreating the biological complexity of living bone marrow (BM) in a single in vitro strategy has faced many challenges. Most bioengineered strategies propose the co-culture of BM cellular components entrapped in different matrices limiting their migration and self-organization capacity or in open scaffolds enabling their escaping. We propose a methodology for fabricating a "human bone marrow-in-a-liquefied-cap...


Liquefied microcapsules compartmentalizing macrophages and umbilical cord-deriv...

Nadine, Sara; Fernandes, Inês; Patrício, Sónia G.; Correia, Clara R.; Mano, João F.

Extraordinary capabilities underlie the potential use of immune cells, particularly macrophages, in bone tissue engineering. Indeed, the depletion of macrophages during bone repair often culminates in disease scenarios. Inspired by the native dynamics between immune and skeletal systems, this work proposes a straightforward in vitro method to bioengineer biomimetic bone niches using biological waste. For that, ...


Minimalist tissue engineering approaches using low material-based bioengineered...

Correia, Clara; Bjorge, Isabel M.; Nadine, Sara; Mano, João F.

From an “over-engineering” era in which biomaterials played a central role, now it is observed to the emergence of “developmental” tissue engineering (TE) strategies which rely on an integrative cell-material perspective that paves the way for cell self-organization. The current challenge is to engineer the microenvironment without hampering the spontaneous collective arrangement ability of cells, while simulta...


An immunomodulatory miniaturized 3D screening platform using liquefied capsules

Nadine, Sara; Correia, Clara R.; Mano, João F.

A critical determinant of successful clinical outcomes is the host's response to the biomaterial. Therefore, the prediction of the immunomodulatory bioperformance of biomedical devices following implantation is of utmost importance. Herein, liquefied capsules are proposed as immunomodulatory miniaturized 3D platforms for the high-content combinatorial screening of different polymers that could be used generical...



Geometrically controlled liquefied capsules for modular tissue engineering stra...

Nadine, Sara; Patrício, Sónia G.; Barrias, Cristina C.; Choi, Insung S.; Matsusaki, Michiya; Correia, Clara R.; Mano, João F.

A plethora of bioinspired cell-laden hydrogels are being explored as building blocks that once assembled are able to create complex and highly hierarchical structures recapitulating the heterogeneity of living tissues. Yet, the resulting 3D bioengineered systems still present key limitations, mainly related with limited diffusion of essential molecules for cell survival, which dictates the failure of most strat...


Dynamic microfactories co-encapsulating osteoblastic and adipose-derived stroma...

Nadine, Sara; Patrício, Sónia G.; Correia, Clara R.; Mano, João F.

Cells with differentiation potential into mesodermal types are the focus of emerging bone tissue engineering (TE) strategies as an alternative autologous source. When the source of cells is extremely limited or not readily accessible, such as in severe injuries, a tissue biopsy may not yield the required number of viable cells. In line, adipose-derived stromal cells (ASCs) quickly became attractive for bone TE,...


Potential role of immunotherapy in advanced non-small-cell lung cancer

De Mello, Ramon Andrade; Veloso, Ana Flavia; Catarina, Paulo Esrom; Nadine, Sara; Antoniou, Georgios

Immuno checkpoint inhibitors have ushered in a new era with respect to the treatment of advanced non-small-cell lung cancer. Many patients are not suitable for treatment with epidermal growth factor receptor tyrosine kinase inhibitors (eg, gefitinib, erlotinib, and afatinib) or with anaplastic lymphoma kinase inhibitors (eg, crizotinib and ceritinib). As a result, anti-PD- 1/PD-L1 and CTLA-4 inhibitors may play...


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