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The high near infrared (NIR) absorption displayed by reduced graphene oxide (rGO) nanostructures renders them a great potential for application in cancer photothermal therapy. However, the production of this material often relies on the use of hydrazine as a reductant, leading to poor biocompatibility and environmental-related issues. In addition, to improve rGO colloidal stability, this material has been functionalized with poly(ethylene glycol). However, recent studies have reported the immunogenicity of poly(ethylene glycol)-based coatings. In this work, the production of rGO, by using dopamine as the reducing agent, was optimized considering the size distribution and NIR absorption of the attained materials. The obtained results unveiled that the rGO produced by using a 1:5 graphene oxide:dopamine weight ratio and a reaction time of 4 h (termed as DOPA-rGO) displayed the highest NIR absorption while retaining its nanometric size distribution. Subsequently, the DOPA-rGO was functionalized with thiol-terminated poly(2-ethyl-2-oxazoline) (P-DOPA-rGO), revealing suitable physicochemical features, colloidal stability and cytocompatibility. When irradiated with NIR light, the P-DOPA-rGO could produce a temperature increase (ΔT) of 36 °C (75 μg/mL; 808 nm, 1.7 W/cm2, 5 min). The photothermal therapy mediated by P-DOPA-rGO was capable of ablating breast cancer cells monolayers (viability < 3%) and could reduce heterotypic breast cancer spheroids' viability to just 30%. Overall, P-DOPA-rGO holds a great potential for application in breast cancer photothermal therapy.

Functionalized graphene oxide (GO) and reduced GO (rGO) based nanomaterials hold a great potential for cancer photothermal therapy. However, their systemic administration has been associated with an accelerated blood clearance and/or with suboptimal tumor uptake. To address these limitations, the local delivery of GO/rGO to the tumor site by 3D matrices arises as a promising strategy. In this work, injectable chitosan-agarose in situ forming thermo-responsive hydrogels incorporating GO (thermogel-GO) or rGO (thermogel-rGO) were prepared for the first time. The hydrogels displayed suitable injectability and gelation time, as well as good physicochemical properties and cytocompatibility. When irradiated with near infrared (NIR) light, the thermogel-rGO produced a 3.8-times higher temperature increase than thermogel-GO, thus decreasing breast cancer cells' viability to 60%. By incorporating an optimized molar ratio of the Doxorubicin:Ibuprofen combination on thermogel-rGO, this formulation mediated a chemo-photothermal effect that further diminished cancer cells' viability to 34%. In addition, the hydrogels' antibacterial activity was further enhanced upon NIR laser irradiation, which is an important feature considering the possible risk of infection at the site of administration. Overall, thermogel-rGO is a promising injectable in situ forming hydrogel for combinatorial chemo-photothermal therapy of breast cancer cells and NIR light enhanced antibacterial applications.

The incidence of fractures and bone-related diseases like osteoporosis has been increasing due to aging of the world's population. Up to now, grafts and titanium implants have been the principal therapeutic approaches used for bone repair/regeneration. However, these types of treatment have several shortcomings, like limited availability, risk of donor-to-recipient infection and tissue morbidity. To overcome these handicaps, new 3D templates, capable of replicating the features of the native tissue, are currently being developed by researchers from the area of tissue engineering. These 3D constructs are able to provide a temporary matrix on which host cells can adhere, proliferate and differentiate. Herein, 3D cylindrical scaffolds were designed to mimic the natural architecture of hollow bones, and to allow nutrient exchange and bone neovascularization. 3D scaffolds were produced with tricalcium phosphate (TCP)/alginic acid (AA) using a Fab@home 3D printer. Furthermore, graphene oxide (GO) was incorporated into the structure of some scaffolds to further enhance their mechanical properties. The results revealed that the scaffolds incorporating GO displayed greater porosity, without impairing their mechanical properties. These scaffolds also presented a controlled swelling profile, enhanced biomineralization capacity and were able to increase the Alkaline Phosphatase (ALP) activity. Such characteristics make TCP/AA scaffolds functionalized with GO promising 3D constructs for bone tissue engineering applications.

The pursuit of effective treatments for metastatic cancer is still one of the most intensive areas of research in the biomedical field. In a not-so-distant past, the scientific community has witnessed the rise of immunotherapy based on immune checkpoint inhibitors (ICIs). This therapeutic modality intends to abolish immunosuppressive interactions, re-establishing T cell responses against metastasized cancer cells. Despite the initial enthusiasm, the ICIs were later found to be associated with low clinical therapeutic outcomes and immune-related side effects. To address these limitations, researchers are exploring the combination of ICIs with nanomaterial-mediated phototherapies. These nanomaterials can accumulate within the tumor and produce, upon interaction with light, a temperature increase (photothermal therapy) and/or reactive oxygen species (photodynamic therapy), causing damage to cancer cells. Importantly, these photothermal-photodynamic effects can pave the way for an enhanced ICI-based immunotherapy by inducing the release of tumor-associated antigens and danger-associated molecular patterns, as well as by relieving tumor hypoxia and triggering a pro-inflammatory response. This progress report analyses the potential of nanomaterial-mediated photothermal-photodynamic therapy in combination with ICIs, focusing on their ability to modulate T cell populations leading to an anti-metastatic abscopal effect and on their capacity to generate immune memory that prevents tumor recurrence.

Nowadays, despite the intensive research performed in the area of skin tissue engineering, the treatment of skin lesions remains a big challenge for healthcare professionals. In fact, none of the wound dressings currently used in the clinic is capable of re-establishing all the native features of skin. An ideal wound dressing must confer protection to the wound from external microorganisms, chemical, and physical aggressions, as well as promote the healing process by stimulating the cell adhesion, differentiation, and proliferation. In recent years different types of wound dressings (such as films, hydrocolloids, hydrogels, micro/nano fibers) have been developed. Among them, electrospun nanofibrous membranes due to their intrinsic properties like high surface area-to-volume ratio, porosity and structural similarity with the skin extracellular matrix have been regarded as highly promising for wound dressings applications. Additionally, the nanofibers available in these membranes can act as drug delivery systems, which prompted the incorporation of biomolecules within their structure to prevent skin infections as well as improve the healing process. In this review, examples of different bioactive molecules that have been loaded on polymeric nanofibers are presented, highlighting the antibacterial biomolecules (e.g. antibiotics, silver nanoparticles and natural extracts-derived products) and the molecules capable of enhancing the healing process (e.g. growth factors, vitamins, and anti-inflammatory molecules).

The incidence of bone disorders, whether due to trauma or pathology, has been trending upward with the aging of the worldwide population. The currently available treatments for bone injuries are rather limited, involving mainly bone grafts and implants. A particularly promising approach for bone regeneration uses rapid prototyping (RP) technologies to produce 3D scaffolds with highly controlled structure and orientation, based on computer-aided design models or medical data. Herein, tricalcium phosphate (TCP)/alginate scaffolds were produced using RP and subsequently their physicochemical, mechanical and biological properties were characterized. The results showed that 60/40 of TCP and alginate formulation was able to match the compression and present a similar Young modulus to that of trabecular bone while presenting an adequate biocompatibility. Moreover, the biomineralization ability, roughness and macro and microporosity of scaffolds allowed cell anchoring and proliferation at their surface, as well as cell migration to its interior, processes that are fundamental for osteointegration and bone regeneration.