Chitosan/Virgin Coconut Oil-Based Emulsions Doped with Photosensitive Curcumin Loaded Capsules: A Functional Carrier to Topical Treatment.

In recent years, there has been a growing interest in developing smart drug delivery systems based on natural resources combined with stimulus-sensitive elements. This trend aims to formulate innovative and sustainable delivery platforms tailored for topical applications. This work proposed the use of layer-by-layer (LbL) methodology to fabricate biocompatible photo-responsive multilayer systems. These systems are composed of a polyoxometalate inorganic salt (POM) ([NaP5W30O110]14-) and a natural origin polymer, chitosan (CHT). Curcumin (CUR), a natural bioactive compound, was incorporated to enhance the functionality of these systems during the formation of hollow capsules. The capsules produced, with sizes between 2-5µm (SEM), were further dispersed into CHT/VCO (virgin coconut oil) emulsion solutions that were casted into molds and dried at 37 °C for 48 h. The system presented a higher water uptake in PBS than in acidic conditions, still significantly lower than that earlier reported to other CHT/VCO-based systems. The drug release profile is not significantly influenced by the medium pH reaching a maximum of 37% ± 1% after 48 h. The antioxidant performance of the designed structures was further studied, suggesting a synergistic beneficial effect resulting from CUR, POM, and VCO individual bioactivities. The increased amount of those excipients released to the media over time promoted an increase in the antioxidant activity of the system, reaching a maximum of 38.1% ± 0.1% after 48 h. This work represents a promising step towards developing advanced, sustainable drug delivery systems for topical applications.

COX-2 inhibitor delivery system aiming intestinal inflammatory disorders.

Selective COX-2 inhibitors such as etoricoxib (ETX) are potentially indicated for the treatment of intestinal inflammatory disorders. However, their systemic administration provokes some off-site secondary effects, decreasing the desirable local effectiveness. To circumvent such limitations, herein an ETX delivery system based on electrospun fibrous meshes (eFMs) was proposed. ETX at different concentrations (1, 2, and 3 mg mL-1) was loaded into eFMs, which not affect the morphology and the mechanical properties of this drug delivery system (DDS). The ETX showed a burst release within the first 12 h, followed by a faster release until 36 h, gradually decreasing over time. Importantly, the ETX studied concentrations were not toxic to human colonic cells (i.e. epithelial and fibroblast). Moreover, the DDS loading the highest concentration of ETX, when tested with stimulated human macrophages, promoted a reduction of PGE2, IL-8 and TNF-α secretion. Therefore, the proposed DDS may constitute a safe and efficient treatment of colorectal diseases promoted by inflammatory disorders associated with COX-2.

3D bioactive ionic liquid-based architectures: An anti-inflammatory approach for early-stage osteoarthritis.

3D bioprinting enables the fabrication of biomimetic cell-laden constructs for cartilage regeneration, offering exclusive strategies for precise pharmacological screenings in osteoarthritis (OA). Synovial inflammation plays a crucial role in OA's early stage and progression, characterized by the increased of the synovial pro-inflammatory mediators and cytokines and chondrocyte apoptosis. Therefore, there is an urgent need to develop solutions for effectively managing the primary events associated with OA. To address these issues, a phenolic-based biocompatible ionic liquid approach, combining alginate (ALG), acemannan (ACE), and cholinium caffeate (Ch[Caffeate]), was used to produce easily printable bioinks. Through the use of this strategy 3D constructs with good printing resolution and high structural integrity were obtained. The encapsulation of chondrocytes like ATDC5 cells provided structures with good cell distribution, viability, and growth, for up to 14 days. The co-culture of the constructs with THP-1 macrophages proved their ability to block pro-inflammatory cytokines (TNF-α and IL-6) and mediators (GM-CSF), released by the cultured cells. Moreover, incorporating the biocompatible ionic liquid into the system significantly improved its bioactive performance without compromising its physicochemical features. These findings demonstrate that ALG/ACE/Ch[Caffeate] bioinks have great potential for bioengineering cartilage tissue analogs. Besides, the developed ALG/ACE/Ch[Caffeate] bioinks protected encapsulated chondrocyte-like cells from the effect of the inflammation, assessed by a co-culture system with THP-1 macrophages. These results support the increasing use of Bio-ILs in the biomedical field, particularly for developing 3D bioprinting-based constructs to manage inflammatory-based changes in OA. STATEMENT OF SIGNIFICANCE: Combining natural resources with active biocompatible ionic liquids (Bio-IL) for 3D printing is herein presented as an approach for the development of tools to manage inflammatory osteoarthritis (OA). We propose combining alginate (ALG), acemannan (ACE), and cholinium caffeate (Ch[Caffeate]), a phenolic-based Bio-IL with anti-inflammatory and antioxidant features, to produce bioinks that allow to obtain 3D constructs with good printing resolution, structural integrity, and that provide encapsulated chondrocyte-like cells good viability. The establishment of a co-culture system using the printed constructs and THP-1-activated macrophages allowed us to study the encapsulated chondrocyte-like cells behaviour within an inflammatory scenario, a typical event in early-stage OA. The obtained outcomes support the beneficial use of Bio-ILs in the biomedical field, particularly for the development of 3D bioprinting-based models that allow the monitoring of inflammatory-based events in OA.

Chitosan/Virgin-Coconut-Oil-Based System Enriched with Cubosomes: A 3D Drug-Delivery Approach.

Emulsion-based systems that combine natural polymers with vegetable oils have been identified as a promising research avenue for developing structures with potential for biomedical applications. Herein, chitosan (CHT), a natural polymer, and virgin coconut oil (VCO), a resource obtained from coconut kernels, were combined to create an emulsion system. Phytantriol-based cubosomes encapsulating sodium diclofenac, an anti-inflammatory drug, were further dispersed into CHT/VCO- based emulsion. Then, the emulsions were frozen and freeze-dried to produce scaffolds. The scaffolds had a porous structure ranging from 20.4 to 73.4 µm, a high swelling ability (up to 900%) in PBS, and adequate stiffness, notably in the presence of cubosomes. Moreover, a well-sustained release of the entrapped diclofenac in the cubosomes into the CHT/VCO-based system, with an accumulated release of 45 ± 2%, was confirmed in PBS, compared to free diclofenac dispersed (80 ± 4%) into CHT/VCO-based structures. Overall, the present approach opens up new avenues for designing porous biomaterials for drug delivery through a sustainable pathway.

Building Fucoidan/Agarose-Based Hydrogels as a Platform for the Development of Therapeutic Approaches against Diabetes.

Current management for diabetes has stimulated the development of versatile 3D-based hydrogels as in vitro platforms for insulin release and as support for the encapsulation of pancreatic cells and islets of Langerhans. This work aimed to create agarose/fucoidan hydrogels to encapsulate pancreatic cells as a potential biomaterial for diabetes therapeutics. The hydrogels were produced by combining fucoidan (Fu) and agarose (Aga), marine polysaccharides derived from the cell wall of brown and red seaweeds, respectively, and a thermal gelation process. The agarose/fucoidan (AgaFu) blended hydrogels were obtained by dissolving Aga in 3 or 5 wt % Fu aqueous solutions to obtain different proportions (4:10; 5:10, and 7:10 wt). The rheological tests on hydrogels revealed a non-Newtonian and viscoelastic behavior, while the characterization confirmed the presence of the two polymers in the structure of the hydrogels. In addition, the mechanical behavior showed that increasing Aga concentrations resulted in hydrogels with higher Young's modulus. Further, the ability of the developed materials to sustain the viability of human pancreatic cells was assessed by encapsulation of the 1.1B4HP cell line for up to 7 days. The biological assessment of the hydrogels revealed that cultured pancreatic beta cells tended to self-organize and form pseudo-islets during the period studied.

Alginate/acemannan-based beads loaded with a biocompatible ionic liquid as a bioactive delivery system.

Combining biomacromolecules with green chemistry principles and clean technologies has proven to be an effective approach for drug delivery, providing a prolonged and sustained release of the encapsulated material. The current study investigates the potential of cholinium caffeate (Ch[Caffeate]), a phenolic-based biocompatible ionic liquid (Bio-IL) entrapped in alginate/acemannan beads, as a drug delivery system able to reduce local joint inflammation on osteoarthritis (OA) treatment. The synthesized Bio-IL has antioxidant and anti-inflammatory actions that, combined with biopolymers as 3D architectures, promote the entrapment and sustainable release of the bioactive molecules over time. The physicochemical and morphological characterization of the beads (ALC, ALAC0,5, ALAC1, and ALAC3, containing 0, 0.5, 1, and 3 %(w/v) of Ch[Caffeate], respectively) revealed a porous and interconnected structure, with medium pore sizes ranging from 209.16 to 221.30 µm, with a high swelling ability (up 2400 %). Ch[Caffeate] significantly improved the antioxidant activities of the constructs by 95 % and 97 % for ALAC1 and ALAC3, respectively, when compared to ALA (56 %). Besides, the structures provided the environment for ATDC5 cell proliferation, and cartilage-like ECM formation, supported by the increased GAGs in ALAC1 and ALAC3 formulations after 21 days. Further, the ability to block the secretion of pro-inflammatory cytokines (TNF-α and IL-6), from differentiated THP-1 was evidenced by ChAL-Ch[Caffeate] beads. These outcomes suggest that the established strategy based on using natural and bioactive macromolecules to develop 3D constructs has great potential to be used as therapeutic tools for patients with OA.

Advanced Polymeric Membranes as Biomaterials Based on Marine Sources Envisaging the Regeneration of Human Tissues.

The self-repair capacity of human tissue is limited, motivating the arising of tissue engineering (TE) in building temporary scaffolds that envisage the regeneration of human tissues, including articular cartilage. However, despite the large number of preclinical data available, current therapies are not yet capable of fully restoring the entire healthy structure and function on this tissue when significantly damaged. For this reason, new biomaterial approaches are needed, and the present work proposes the development and characterization of innovative polymeric membranes formed by blending marine origin polymers, in a chemical free cross-linking approach, as biomaterials for tissue regeneration. The results confirmed the production of polyelectrolyte complexes molded as membranes, with structural stability resulting from natural intermolecular interactions between the marine biopolymers collagen, chitosan and fucoidan. Furthermore, the polymeric membranes presented adequate swelling ability without compromising cohesiveness (between 300 and 600%), appropriate surface properties, revealing mechanical properties similar to native articular cartilage. From the different formulations studied, the ones performing better were the ones produced with 3 % shark collagen, 3% chitosan and 10% fucoidan, as well as with 5% jellyfish collagen, 3% shark collagen, 3% chitosan and 10% fucoidan. Overall, the novel marine polymeric membranes demonstrated to have promising chemical, and physical properties for tissue engineering approaches, namely as thin biomaterial that can be applied over the damaged articular cartilage aiming its regeneration.

Tailoring Natural-Based Oleogels Combining Ethylcellulose and Virgin Coconut Oil.

Oleogels are becoming an attractive research field, since they have recently been shown to be feasible for the food and pharmaceutical sectors and provided some insights into the biomedical area. In this work, edible oleogels were tailored through the combination of ethylcellulose (EC), a gelling agent, with virgin coconut oil (VCO), vegetable oil derived from coconut. The influence of the different EC and VCO ratios on the structural, physical, and thermal properties of the oleogels was studied. All EC/VCO-based oleogels presented a stable network with a viscoelastic nature, adequate structural stability, modulable stiffness, high oil-binding capability, antioxidant activity, and good thermal stability, evidencing the EC and VCO's good compatibility.

Metronidazole Delivery Nanosystem Able To Reduce the Pathogenicity of Bacteria in Colorectal Infection.

Metronidazole (MTZ) is a drug potentially used for the treatment of intestinal infections, namely, the ones caused by colorectal surgery. The traditional routes of administration decrease its local effectiveness and present off-site effects. To circumvent such limitations, herein a drug delivery system (DDS) based on MTZ-loaded nanoparticles (NPs) immobilized at the surface of electrospun fibrous meshes is proposed. MTZ at different concentrations (1, 2, 5, and 10 mg mL-1) was loaded into chitosan-sodium tripolyphosphate NPs. The MTZ loaded into NPs at the highest concentration showed a quick release in the first 12 h, followed by a gradual release. This DDS was not toxic to human colonic cells. When tested against different bacterial strains, a significant reduction of Escherichia coli and Staphylococcus aureus was observed, but no effect was found against Enterococcus faecalis. Therefore, this DDS offers high potential to locally prevent the occurrence of infections after colorectal anastomosis.

Surface Functionalization of Ureteral Stents-Based Polyurethane: Engineering Antibacterial Coatings.

Bacterial colonization of polyurethane (PU) ureteral stents usually leads to severe and challenging clinical complications. As such, there is an increasing demand for an effective response to this unmet medical challenge. In this study, we offer a strategy based on the functionalization of PU stents with chitosan-fatty acid (CS-FA) derivatives to prevent bacterial colonization. Three different fatty acids (FAs), namely stearic acid (SA), oleic acid (OA), and linoleic acid (LinA), were successfully grafted onto chitosan (CS) polymeric chains. Afterwards, CS-FA derivatives-based solutions were coated on the surface of PU stents. The biological performance of the modified PU stents was evaluated against the L929 cell line, confirming negligible cytotoxicity of the developed coating formulations. The antibacterial potential of coated PU stents was also evaluated against several microorganisms. The obtained data indicate that the base material already presents an adequate performance against Staphylococcus aureus, which slightly improved with the coating. However, the performance of the PU stents against Gram-negative bacteria was markedly increased with the surface functionalization approach herein used. As a result, this study reveals the potential use of CS-FA derivatives for surface functionalization of ureteral PU stents and allows for conjecture on its successful application in other biomedical devices.

Chitosan/ß-TCP composites scaffolds coated with silk fibroin: a bone tissue engineering approach.

Bone regeneration and natural repair are long-standing processes that can lead to uneven new tissue growth. By introducing scaffolds that can be autografts and/or allografts, tissue engineering provides new approaches to manage the major burdens involved in this process. Polymeric scaffolds allow the incorporation of bioactive agents that improve their biological and mechanical performance, making them suitable materials for bone regeneration solutions. The present work aimed to create chitosan/beta-tricalcium phosphate-based scaffolds coated with silk fibroin and evaluate their potential for bone tissue engineering. Results showed that the obtained scaffolds have porosities up to 86%, interconnectivity up to 96%, pore sizes in the range of 60-170 µm, and a stiffness ranging from 1 to 2 MPa. Furthermore, when cultured with MC3T3 cells, the scaffolds were able to form apatite crystals after 21 d; and they were able to support cell growth and proliferation up to 14 d of culture. Besides, cellular proliferation was higher on the scaffolds coated with silk. These outcomes further demonstrate that the developed structures are suitable candidates to enhance bone tissue engineering.

Physicochemical features assessment of acemannan-based ternary blended films for biomedical purposes.

The exploitation of natural origin macromolecules, as complex physical mixtures or drugs, increases in biomedical or tissue engineering (TE) solutions. Aloe Vera is a highly explored medicinal plant, from which the main polysaccharide is acemannan (ACE). The ACE combination with chitosan and alginate results in interactions that lead to mixed junction zones formation, predicting membrane functionality improvement. This work proposes the development and characterization of ACE-based blended films as a promising strategy to design a nature-derived bioactive platform. The results confirmed that stable complex polyelectrolyte structures were formed through different intermolecular interactions. The films present good dimensional stability, flexibility, an adequate swelling ability with mostly radial water uptake, and a sustainable ACE release to the medium. Positive biological performance of the ACE-based blended films with L929 cells also suggested that they can be applied in TE solutions, with the potential to act as bioactive topical platforms.

Approach on chitosan/virgin coconut oil-based emulsion matrices as a platform to design superabsorbent materials.

The design of innovative pharmaceutical products, able to reach unexplored market niches, requires natural materials use with improved swelling and moisture properties. Herein, chitosan (CHT), a natural polymer, was combined with virgin coconut oil (VCO), a resource extracted from coconut kernels, to develop emulsion-based films for biomedical purposes. The film's properties were tuned by changing VCO concentrations, and the structural, morphological, and physical properties of the films were evaluated. The CHT/VCO-based film morphology showed the presence of VCO droplets at different sizes, both in the surface and inner part. Moreover, the capability to develop CHT/VCO-films as superabsorbent materials was shown. The film extracts cytotoxicity was assessed using human adipose stem cells, and metabolic activity was confirmed. The findings suggest that incorporating a small volume of VCO into the CHT system, superabsorbent materials with the potential to be applied in biomedical devices that require high swelling properties, can be developed.

Marine-Derived Polymers in Ionic Liquids: Architectures Development and Biomedical Applications.

Marine resources have considerable potential to develop high-value materials for applications in different fields, namely pharmaceutical, environmental, and biomedical. Despite that, the lack of solubility of marine-derived polymers in water and common organic solvents could restrict their applications. In the last years, ionic liquids (ILs) have emerged as platforms able to overcome those drawbacks, opening many routes to enlarge the use of marine-derived polymers as biomaterials, among other applications. From this perspective, ILs can be used as an efficient extraction media for polysaccharides from marine microalgae and wastes (e.g., crab shells, squid, and skeletons) or as solvents to process them in different shapes, such as films, hydrogels, nano/microparticles, and scaffolds. The resulting architectures can be applied in wound repair, bone regeneration, or gene and drug delivery systems. This review is focused on the recent research on the applications of ILs as processing platforms of biomaterials derived from marine polymers.

Engineered tubular structures based on chitosan for tissue engineering applications.

The development of versatile tubular structures is a subject of broad interest in tissue engineering applications. Herein, we demonstrate the production of tubular structures based on chitosan through a combination of dipping, freeze-drying and supercritical technology approaches. The combination of these techniques yields versatile tubes with a perfectly defined hollow imprint, which upon chemical cross-linking with genipin acquire enhanced mechanical properties (Young Modulus ( E) and ultimate tensile stress (σmax)), as well as improved stability in wet conditions. The biological performance reveals that cells remain attached, well-spread and viable on the surface of cross-linked tubes. As so, is envisioned that our methodology opens up new avenues on tissue engineering approaches, where the design of tubular structures with tuned length, diameter and elasticity is required.

Light responsive multilayer surfaces with controlled spatial extinction capability.

Multilayer systems obtained using the Layer-by-Layer (LbL) technology have been proposed for a variety of biomedical applications in tissue engineering and regenerative medicine. LbL assembly is a simple and highly versatile method to modify surfaces and fabricate robust and highly-ordered nanostructured coatings over almost any type of substrates and with a wide range of substances. The incorporation of polyoxometalate (POM) inorganic salts as constituents of the layers presents a possibility of promoting light-stimuli responses in LbL substrates. We propose the design of a biocompatible photo-responsive multilayer system based on a Preyssler-type POM ([NaP5W30O110]14-) and a natural origin polymer, chitosan, using the LbL methodology. The photo-reduction properties of the POM allow the spatially controlled disruption of the assembled layers due to the weakening of the electrostatic interactions between the layers. This system has found applicability in detaching devices, such as the cell sheet technology, which may solve the drawbacks actually found in other cell treatment proposals.