Functionalized polyester-based materials as UV curable adhesives

UV curable adhesives offer major advantages in comparison to other polymeric based adhesive systems, such as fast-curing rate and control of the polymerization heat evolution, being ideal for application on damaged tissues. Herein, functionalized polymers were prepared by modifying polycaprolactone diol (PCL) with an isocyanate-functional unsaturated acrylic ester, Laromer® 9000, using two different proportions. These functionalized materials were chemically/physically characterized and, after the addition of a biocompatible photoinitiator (Irgacure® 2959), were crosslinked by UV light irradiation. Such procedure allows the obtention of flexible transparent films. Films’ properties such as swelling, hydrolytic degradation, thermal stability, surface energy and adhesive capacity were evaluated. Furthermore, to assess the applicability of the films in biomedical applications, their haemocompatibility and biocompatibility were determined using human dermal fibroblasts as model.info:eu-repo/semantics/acceptedVersio

Optical clearing methods: An overview of the techniques used for the imaging of 3D spheroids

Spheroids have emerged as in vitro models that reproduce in a great extent the architectural microenvironment found in human tissues. However, the imaging of 3D cell cultures is highly challenging due to its high thickness, which results in a light-scattering phenomenon that limits light penetration. Therefore, several optical clearing methods, widely used in the imaging of animal tissues, have been recently explored to render spheroids with enhanced transparency. These methods are aimed to homogenize the microtissue refractive index (RI) and can be grouped into four different categories, namely (a) simple immersion in an aqueous solution with high RI; (b) delipidation and dehydration followed by RI matching; (c) delipidation and hyperhydration followed by RI matching; and (d) hydrogel embedding followed by delipidation and RI matching. In this review, the main optical clearing methods, their mechanism of action, advantages, and disadvantages are described. Furthermore, the practical examples of the optical clearing methods application for the imaging of 3D spheroids are highlighted.info:eu-repo/semantics/publishedVersio

Production and characterization of a novel asymmetric 3D printed construct aimed for skin tissue regeneration

Skin is a complex organ that act as the first protective barrier against any external threat. After an injury occurs, its structure and functions must be re-established as soon as possible. Among different available skin substitutes (epidermal, dermal and dermo-epidermal), none of them is fully capable of reproducing/re-establishing all the features and functions of native skin. Herein, a three-dimensional skin asymmetric construct (3D_SAC) was produced using electrospinning and 3D bioprinting techniques. A poly(caprolactone) and silk sericin blend was electrospun to produce a top layer aimed to mimic the epidermis features, i.e. to provide a protective barrier against dehydration and hazard agents. In turn, the dermis like layer was formed by printing layer-by-layer a chitosan/sodium alginate hydrogel. The results obtained in the in vitro assays revealed that the 3D_SAC display a morphology, porosity, mechanical properties, wettability, antimicrobial activity and a cytotoxic profile that grants their application as a skin substitute during the healing process.info:eu-repo/semantics/publishedVersio

Overview of stimuli-responsive mesoporous organosilica nanocarriers for drug delivery

The application of nanomaterials is regarded nowadays as a highly promising approach for overcoming the limitations of the currently available cancer treatments, contributing for the creation of more effective, precise, and safer therapies. In the last years, organosilica nanoparticles arisen as alternatives to the most common mesoporous silica nanoparticles. The organosilica nanoparticles combine the advantages of the mesoporous silica, such as structural stability and mesoporous structure, with the increased biocompatibility and biodegradability of organic materials. Therefore, the variety of organic bridges that can be incorporated into the silica matrix allowed the development of new and exciting compositions, properties, and functions for improving the therapeutic effectiveness of the anticancer nanomedicines. In this review, the strategies that have been explored to create stimuli-responsive organosilica-based drug delivery systems are highlighted, describing the practical approaches and mechanisms controlling the drug release. Additionally, the organosilica nanoparticles surface modifications aimed for increasing the blood circulation time and the tumor targeting are also described.info:eu-repo/semantics/publishedVersio

Graphene family nanomaterials for application in cancer combination photothermal therapy

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.grant UBI-Santander/Tottainfo:eu-repo/semantics/acceptedVersio

Electrospun Asymmetric Membranes as Promising Wound Dressings: A Review

Despite all the efforts that have been done up to now, the currently available wound dressings are still unable to fully re-establish all the structural and functional properties of the native skin. To overcome this situation, researchers from the tissue engineering area have been developing new wound dressings (hydrogels, films, sponges, membranes) aiming to mimic all the features of native skin. Among them, asymmetric membranes emerged as a promising solution since they reproduce both epidermal and dermal skin layers. Wet or dry/wet phase inversion, scCO2-assisted phase inversion, and electrospinning have been the most used techniques to produce such a type of membranes. Among them, the electrospinning technique, due to its versatility, allows the development of multifunctional dressings, using natural and/or synthetic polymers, which resemble the extracellular matrix of native skin as well as address the specific requirements of each skin layer. Moreover, various therapeutic or antimicrobial agents have been loaded within nanofibers to further improve the wound healing performance of these membranes. This review article provides an overview of the application of asymmetric electrospun membranes as wound dressings displaying antibacterial activity and as delivery systems of biomolecules that act as wound healing enhancers.info:eu-repo/semantics/publishedVersio

Optimization of gold core-mesoporous silica shell functionalization with TPGS and PEI for cancer therapy

Photothermal therapy (PTT) has captured the attention of different researchers around the world, since the application of NIR light responsive-nanomaterials has shown promising results in cancer therapy. Gold-core mesoporous silica shell (Au-MSS) nanoparticles allow the combination of gold mediated PTT with the drug delivery in order to improve their therapeutic potential. In this study, two different methodologies, electrostatic or chemical linkage, were explored to functionalize Au-MSS nanorods with TPGS and PEI. For that purpose, the TPGS and PEI were chemically coupled to each other or modified with 3-(triethoxysilyl)propyl isocyanate. The produced Au-MSS nanorods display a uniform morphology and a well-defined gold nucleus and silica shell. Further, the particles surface charge was dependent on the synthesis methodology. The particles modified by electrostatic interactions (Au-MSS/TPGS-PEI) were slightly negative (−16.9 and −5.1 mV) whereas the formulations produced by chemical linkage (Au-MSS/TPGS/PEI) resulted in positively charged nanoparticles (30.9 and 6.8 mV). The successful incorporation of the polymers was confirmed by Fourier Transformed Infrared spectroscopy and thermogravimetric analysis. Moreover, the Au-MSS functionalization did not affect the particles PTT capacity. However, the Au-MSS/TPGS/PEI nanorods displayed a decreased drug encapsulation efficiency. In vitro assays demonstrated the cytocompatibility of Au-MSS up to concentrations of 200 μg/mL, however the positively charged formulations only remained biocompatible until 100 and 125 μg/mL. Overall, the attained data confirm the successful modification of Au-MSS nanorods with TPGS and PEI as well as their applicability as PTT and drug delivery agents.info:eu-repo/semantics/publishedVersio

Photocurable Polymeric Blends for Surgical Application

The preparation of photocrosslinkable bioadhesives synthesized from oligomers of lactic acid and polycaprolactone (PCL), both functionalized with 2-isocyanoethyl acrylate (AOI), were studied. The obtained modified macromers of LA-AOI (mLA) and PCL-AOI (mCL) were chemically characterized by 1H NMR and used to formulate polymeric blends with different mass proportions, 1:1, 1:2 and 2:1, respectively. Subsequently, the produced blends were crosslinked, considering two UV irradiation times: 30 and 120 s. After their production, the thermal and mechanical properties of bioadhesives were assessed, where upon the rheology, gel content, hydrolytic degradation and dynamic contact angles were determined. Furthermore, the cytotoxic profile of bioadhesives was evaluated in contact with human dermal fibroblasts cells, whereas their antibacterial effect was studied monitoring Escherichia coli and S. aureus growth. Overall, flexible and resistant films were obtained, presenting promising features to be used as surgical bioadhesives.info:eu-repo/semantics/publishedVersio

Lignin-enriched tricalcium phosphate/sodium alginate 3D scaffolds for application in bone tissue regeneration

The bone is a connective, vascularized, and mineralized tissue that confers protection to organs, and participates in the support and locomotion of the human body, maintenance of homeostasis, as well as in hematopoiesis. However, throughout the lifetime, bone defects may arise due to traumas (mechanical fractures), diseases, and/or aging, which when too extensive compromise the ability of the bone to self-regenerate. To surpass such clinical situation, different therapeutic approaches have been pursued. Rapid prototyping techniques using composite materials (consisting of ceramics and polymers) have been used to produce customized 3D structures with osteoinductive and osteoconductive properties. In order to reinforce the mechanical and osteogenic properties of these 3D structures, herein, a new 3D scaffold was produced through the layer-by-layer deposition of a tricalcium phosphate (TCP), sodium alginate (SA), and lignin (LG) mixture using the Fab@Home 3D-Plotter. Three different TCP/LG/SA formulations, LG/SA ratio 1:3, 1:2, or 1:1, were produced and subsequently evaluated to determine their suitability for bone regeneration. The physicochemical assays demonstrated that the LG inclusion improved the mechanical resistance of the scaffolds, particularly in the 1:2 ratio, since a 15 % increase in the mechanical strength was observed. Moreover, all TCP/LG/SA formulations showed an enhanced wettability and maintained their capacity to promote the osteoblasts' adhesion and proliferation as well as their bioactivity (formation of hydroxyapatite crystals). Such results support the LG inclusion and application in the development of 3D scaffolds aimed for bone regeneration.info:eu-repo/semantics/publishedVersio

Optimization of the GSH-Mediated Formation of Mesoporous Silica-Coated Gold Nanoclusters for NIR Light-Triggered Photothermal Applications

Cancer light-triggered hyperthermia mediated by nanomaterials aims to eliminate cancer cells by inducing localized temperature increases to values superior to 42 C, upon irradiation with a laser. Among the different nanomaterials with photothermal capacity, the gold-based nanoparticles have been widely studied due to their structural plasticity and advantageous physicochemical properties. Herein, a novel and straightforward methodology was developed to produce gold nanoclusters coated with mesoporous silica (AuMSS), using glutathione (GSH) to mediate the formation of the gold clusters. The obtained results revealed that GSH is capable of triggering and control the aggregation of gold nanospheres, which enhanced the absorption of radiation in the NIR region of the spectra. Moreover, the produced AuMSS nanoclusters mediated a maximum temperature increase of 20 C and were able to encapsulate a drug model (acridine orange). In addition, these AuMSS nanoclusters were also biocompatible with both healthy (fibroblasts) and carcinogenic (cervical cancer) cells, at a maximum tested concentration of 200 g/mL. Nevertheless, the AuMSS nanoclusters’ NIR light-triggered heat generation successfully reduced the viability of cervical cancer cells by about 80%. This confirms the potential of the AuMSS nanoclusters to be applied in cancer therapy, namely as theragnostic agents.info:eu-repo/semantics/publishedVersio