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Progress in the nanotechnology field has led to the development of a new class of materials capable of producing a temperature increase triggered by near infrared light. These photothermal nanostructures have been extensively explored in the ablation of cancer cells. Nevertheless, the available data in the literature have exposed that systemically administered nanomaterials have a poor tumor-homing capacity, hindering their full therapeutic potential. This paradigm shift has propelled the development of new injectable hydrogels for the local delivery of nanomaterials aimed at cancer photothermal therapy. These hydrogels can be assembled at the tumor site after injection (in situforming) or can undergo a gel–sol–gel transition during injection (shear-thinning/self-healing). Besides incorporating photothermal nanostructures, these injectable hydrogels can also incorporate or be combined with other agents, paving the way for an improved therapeutic outcome. This review analyses the application of injectable hydrogels for the local delivery of nanomaterials aimed at cancer photothermal therapy as well as their combination with photodynamic-, chemo-, immuno- and radio-therapies.

Despite aiming to improve the healing process, the wound dressings that have been developed thus far still present high production costs, uncontrolled drug delivery, and are unable to fully re-establish all features of native skin. In this field, the development of light-responsive dressings has been emerging due to the possibility of controlling the delivery of therapeutic agents both in time and space. Moreover, this strategy has also been explored to guide the materials’ polymerization/crosslinking, as well as to mediate therapeutic approaches based on photothermal or photodynamic effects. Among the different approaches, the utilization of near-infrared (NIR) light holds a high translational potential due to the minimal interactions with the biological components and higher penetration capacity in human tissues. In this way, different biomaterials responsive to NIR light have been produced and explored in the production of active wound dressings. Therefore, this review aims to provide an overview of the advantages of NIR light to the wound healing process, in particular, its thermal, photodynamic, photobiomodulation, and imaging potential. Furthermore, the antibacterial, drug-release, and cellular responses that can be obtained with the application of NIR-responsive wound dressings are also described focusing on its impact on the healing process.

Cancer photothermal therapy (PTT) has captured the attention of researchers worldwide due to its localized and trigger-activated therapeutic effect. In this field, nanomaterials capable of converting the energy of the irradiation light into heat have been showing promising results in several pre-clinical and clinical assays. Such a therapeutic modality takes advantage of the innate capacity of nanomaterials to accumulate in the tumor tissue and their capacity to interact with NIR laser irradiation to exert a therapeutic effect. Therefore, several nanostructures composed of different materials and organizations for mediating a photothermal effect have been developed. In this review, the most common inorganic nanomaterials, such as gold, carbon-based materials, tungsten, copper, molybdenum, and iron oxide, which have been explored for mediating a tumor-localized photothermal effect, are summarized. Moreover, the physicochemical parameters of nanoparticles that influence the PTT effectiveness are discussed and the recent clinical advances involving inorganic nanomaterial-mediated cancer photothermal therapy are also presented.

Combining hyperthermia with other therapies holds a great potential for improving cancer treatment. In this approach, the increase in the body temperature can exert a therapeutic effect on cells and/or enhance the effectiveness of anticancer agents. However, the conventional methodologies available to induce hyperthermia cannot confine a high temperature increase to the tumor-site while maintaining healthy tissues unexposed and ensuring minimal invasiveness. To overcome these limitations, combination photothermal therapy (PTT) mediated by graphene family nanomaterials (GFN) has been showing promising results. Such is owed to the ability of GFN to accumulate at the tumor site and convert near infrared light into heat, enabling a hyperthermia with a high spatial-temporal resolution. Furthermore, GFN can also incorporate different therapeutic agents on their structure for delivery purposes to cancer cells. In this way, the combination PTT mediated by GFN can result in an improved therapeutic effect. In this review, the combination of GFN mediated PTT with chemo-, photodynamic-, gene-, radio-, and immuno-therapies is examined. Furthermore, the main parameters that influence these types of combination approaches are also analyzed, with emphasis on the photothermal potential of GFN and on the vascular and cellular effects produced by the temperature increase mediated by GFN.

Bioinspired and adhesive multilayer membranes are produced using the layer-by-layer (LbL) assembly of chitosan (CHT), alginate (ALG) and hyaluronic acid modified with dopamine (HA-DN). Freestanding multilayer membranes without DN are also produced as a control. The success of the synthesis of HA-DN was confirmed using UV-visible spectroscopy. Scanning electron microscopy images indicate that the surface of the DN-containing membranes is more porous than the control ones; they also present a higher average thickness value for the same number of CHT/ALG/CHT/HA(-DN) tetralayers (n= 100). Also, water uptake, mechanical strength and adhesion are enhanced with the introduction of DN moieties along the nano-layers. Besides, human dermal fibroblast viability, enhanced adhesion and proliferation were confirmed by immunofluorescence assays and by measuring both the metabolic activity and DNA content. Moreover, in vivoassays with such kinds of DN-containing multilayer membranes were performed; the application of these membranes in the treatment of dermal wounds induced in Wistar rats results in the highest decrease of inflammation of rat skin, compared with the control conditions. Overall, this investigation suggests that these mussel-inspired freestanding multilayer membranes may enhance either their mechanical performance or cellular adhesion and proliferation, leading to an improved wound healing process, being a promising material to restore the structural and functional properties of wounded skin.

Cancer nanomedicines are designed to encapsulate different therapeutic agents, prevent their premature release, and deliver them specifically to cancer cells, due to their ability to preferentially accumulate in tumor tissue. However, after intravenous administration, nanoparticles immediately interact with biological components that facilitate their recognition by the immune system, being rapidly removed from circulation. Reports show that less than 1% of the administered nanoparticles effectively reach the tumor site. This suboptimal pharmacokinetic profile is pointed out as one of the main factors for the nanoparticles' suboptimal therapeutic effectiveness and poor translation to the clinic. Therefore, an extended blood circulation time may be crucial to increase the nanoparticles' chances of being accumulated in the tumor and promote a site‐specific delivery of therapeutic agents. For that purpose, the understanding of the forces that govern the nanoparticles' interaction with biological components and the impact of the physicochemical properties on the in vivo fate will allow the development of novel and more effective nanomedicines. Therefore, in this review, the nano–bio interactions are summarized. Moreover, the application of cell‐derived vesicles for extending the blood circulation time and tumor accumulation is reviewed, focusing on the advantages and shortcomings of each cell source. The creation of biomimetic coatings based on cell‐derived vesicles is an emerging concept to improve the nanomaterials' biological performance. Cell‐derived vesicles retain the antigenic diversity of the source cell, providing immune escape, targeting ability, and cellular related‐functions. Therefore, this review summarizes the application of cell‐derived vesicles, highlighting their potential for increasing the nanomaterials' blood circulation and tumor accumulation.

While developing tissue engineering strategies, inflammatory response caused by biomaterials is an unavoidable aspect to be taken into consideration, as it may be an early limiting step of tissue regeneration approaches. We demonstrate the application of flat and flexible films exhibiting patterned high-contrast wettability regions as implantable platforms for the high-content in vivostudy of inflammatory response caused by biomaterials. Screening biomaterials by using high-throughput platforms is a powerful method to detect hit spots with promising properties and to exclude uninteresting conditions for targeted applications. High-content analysis of biomaterials has been mostly restricted to in vitrotests where crucial information is lost, as in vivoenvironment is highly complex. Conventional biomaterials implantation requires the use of high numbers of animals, leading to ethical questions and costly experimentation. Inflammatory response of biomaterials has also been highly neglected in high-throughput studies. We designed an array of 36 combinations of biomaterials based on an initial library of four polysaccharides. Biomaterials were dispensed onto biomimetic superhydrophobic platforms with wettable regions and processed as freeze-dried three-dimensional scaffolds with a high control of the array configuration. These chips were afterward implanted subcutaneously in Wistar rats. Lymphocyte recruitment and activated macrophages were studied on-chip, by performing immunocytochemistry in the miniaturized biomaterials after 24 h and 7 days of implantation. Histological cuts of the surrounding tissue of the implants were also analyzed. Localized and independent inflammatory responses were detected. The integration of these data with control data proved that these chips are robust platforms for the rapid screening of early-stage in vivobiomaterials' response.

Cell-based therapies for regenerative medicine have been characterized by the low retention and integration of injected cells into host structures. Cell immobilization in hydrogels for target cell delivery has been developed to circumvent this issue. In this work mesenchymal stem cells isolated from Wistar rats bone marrow (rMSCs) were immobilized in alginate beads fabricated using an innovative approach involving the gellification of the liquid precursor droplets onto biomimetic superhydrophobic surfaces without the need of any precipitation bath. The process occurred in mild conditions preventing the loss of cell viability. Furthermore, fibronectin (FN) was also immobilized inside alginate beads with high efficiency in order to mimic the composition of the extracellular matrix. This process occurred in a very fast way (around 5 min), at room temperature, without aggressive mechanical strengths or particle aggregation. The methodology employed allowed the production of alginate beads exhibiting a homogenous rMSCs and FN distribution. Encapsulated rMSCs remained viable and were released from the alginate for more than 20 days. In vivoassays were also performed, by implanting these particles in a calvarial bone defect to evaluate their potential for bone tissue regeneration. Microcomputed tomography and histological analysis results showed that this hybrid system accelerated bone regeneration process. The methodology employed had a dual role by preventing cell and FN loss and avoiding any contamination of the beads or exchange of molecules with the surrounding environment. In principle, the method used for cell encapsulation could be extended to other systems aimed to be used in tissue regeneration strategies.

Blau: Biokompatible und biologisch abbaubare, wasserlösliche Dendrimere mit Harnstoffgruppen im Inneren und Aminogruppen auf der Außenseite wurden in überkritischem Kohlendioxid synthetisiert (siehe ein Dendrimer der ersten Generation). Diese neue Klasse von Dendrimeren zeigt eine pH‐abhängige intrinsische blaue Fluoreszenz bei niedrigen Konzentrationen, was sie zu vielversprechenden Zellmarkern macht.

Blue: Biocompatible and biodegradable water‐soluble dendrimers comprising ureas within the interior and amino groups on the periphery were synthesized in supercritical carbon dioxide (dendrimer of generation 1 shown in picture). This novel class of dendrimers shows a pH‐dependent intrinsic blue fluorescence at very low concentrations, which makes them potential polymeric fluorescent cell markers.

The facultative aerobic bacterium Shewanella frigidimarina produces a small c-type tetrahaem cytochrome (86 residues) under anaerobic growth conditions. This protein is involved in the respiration of iron and shares 42% sequence identity with the N-terminal domain of a soluble flavocytochrome, isolated from the periplasm of the same bacterium, which also contains four c-type haem groups. The thermodynamic properties of the redox centres and of an ionizable centre in the tetrahaem cytochrome were determined using NMR and visible spectroscopy techniques. This is the first detailed thermodynamic study performed on a tetrahaem cytochrome isolated from a facultative aerobic bacterium and reveals that this protein presents unique features. The redox centres have negative and different redox potentials, which are modulated by redox interactions between the four haems (covering a range of 8—56mV) and by redox—Bohr interactions between the haems and an ionizable centre (-4 to −36mV) located in close proximity to haem III. All of the interactions between the five centres are clearly dominated by electrostatic effects and the microscopic reduction potential of haem III is the one most affected by the oxidation of the other haems and by the protonation state of the molecule. Altogether, this study indicates that the tetrahaem cytochrome isolated from S. frigidimarina (Sfc) has the thermodynamic properties to work as an electron wire between its redox partners. Considering the high degree of sequence identity between Sfc and the cytochrome domain of flavocytochrome c3, the structural similarities of the haem core, and that the macroscopic potentials are also identical, the results obtained in this work are rationalized in order to put forward a putative redox model for flavocytochrome c3.

Developing technologies that allow the simultaneous diagnosis and treatment of cancer (theragnostic) has been the quest of numerous interdisciplinary research teams. In this context, nanomaterials incorporating prototypic near infrared (NIR)‐light responsive heptamethine cyanines have been showing very promising results for cancer theragnostic. The precisely engineered features of these nanomaterials endow them with the ability to achieve a high tumor accumulation, enabling a tumor's visualization by NIR fluorescence and photoacoustic imaging modalities. Upon interaction with NIR light, the tumor‐homed heptamethine cyanine‐incorporating nanomaterials can also produce a photothermal/photodynamic effect with a high spatio‐temporal resolution and minimal side effects, leading to an improved therapeutic outcome. This progress report analyses the application of nanomaterials incorporating prototypic NIR‐light responsive heptamethine cyanines (IR775, IR780, IR783, IR797, IR806, IR808, IR820, IR825, IRDye 800CW, and Cypate) for cancer photothermal therapy, photodynamic therapy, and imaging. Overall, the continuous development of nanomaterials incorporating the prototypic NIR absorbing heptamethine cyanines will cement their phototheragnostic capabilities. Nanomaterials incorporating prototypic heptamethine cyanines have the ability to be used for cancer photothermal and photodynamic therapies as well as for tumor imaging (near infrared fluorescence and photoacoustic imaging). This progress report analyses the optical properties of the different prototypic heptamethine cyanines, focusing on their incorporation into nanomaterials in order to achieve an improved cancer phototheragnostic.