Zinc ions and N-acetylcysteine (NAC) are bioactive agents with key physiological roles. When associated with biomacromolecules such as silk fibroin (SF), they offer a promising pathway for advanced biomedical applications. This study reports the synthesis of layered zinc hydroxide (LZH) intercalated with NAC as well as the development of LZH-NAC/SF scaffolds. The synthesis of LZH-NAC was conducted using a constant-pH method, and experimental parameters were controlled to obtain a monophasic LZH. Comprehensive structural, spectroscopic, textural, and thermal characterisation confirmed the successful intercalation of NAC into the LZH. The employed methodology enabled the production of an LZH-NAC nanomaterial with an encapsulation efficiency of approximately 80 % by mass and a loading capacity of around 30 %. To evaluate its biomedical potential, LZH-NAC/SF 3D composite scaffolds were prepared by dispersing LZH-NAC in SF solution, followed by freezing and freeze-drying. The average pore sizes observed in the scaffolds ranged from 75 to 87 mu m, and the swelling capacity was approximately 1700 % after incubation in phosphate-buffered saline (pH 7.4). Cytocompatibility assays revealed that LZH-NAC/SF scaffolds supported cell viability at a zinc concentration of 0.189 mg/mL, similar to that of the SF and NAC/SF scaffolds. These results underscore the potential of LZH-NAC/SF scaffolds as multifunctional biomaterials for the controlled delivery of therapeutic agents, with significant implications for tissue engineering and drug delivery systems.

Green manufacturing approaches and bioinspired materials are revolutionizing the healthcare sector by enabling the development of sustainable, high-performance biomaterials. Lepidopteran silk is an excellent natural material that combines adaptability, biocompatibility, and mechanical strength. The toolkit for turning silk into biomedical constructs has grown with the introduction of green solvents, particularly ionic liquids and deep eutectic solvents. Owing to their properties, such as negligible vapor pressure, chemical tunability, and recyclability, these solvents enable fine control over molecular conformation and the regeneration of silk proteins. This review brings together recent advances in the use of green solvents to produce tunable silk-based 2D/3D structures with enhanced chemical and biological performance. It also examines how green solvents influence intermolecular interactions in silk and their implications for therapeutic use. Remaining challenges, such as process reproducibility and scalability, are discussed, and an outline of future trends is presented to establish green solvent-based silk biomaterials as suitable processing platforms for regenerative medicine. This review brings together recent advances in the use of green solvents to produce tunable silk-based 2D/3D structures with enhanced chemical and biological performance. It also examines how green solvents influence intermolecular interactions in silk and their implications for therapeutic use.

Osteochondral defects present significant challenges for effective tissue regeneration due to the complex composition of bone and cartilage. To address this challenge, this study presents the fabrication of hierarchical scaffolds combining chitosan/β-tricalcium phosphate (β-TCP) to simulate a bone-like layer, interconnected with a silk fibroin layer to mimic cartilage, thus replicating the cartilage-like layer to mimic the native osteochondral tissue architecture. The scaffolds were produced by freeze-drying and then crosslinking with genipin. They have a crosslinking degree of up to 24%, which promotes a structural rearrangement and improved connection between the different layers. Micro-CT analysis demonstrated that the structures have distinct porosity values on their top layer (up to 84%), interface (up to 65%), and bottom layer (up to 77%) and are dependent on the concentration of β-tricalcium phosphate used. Both layers were confirmed to be clearly defined by the distribution of the components throughout the constructs, showing adequate mechanical properties for biomedical use. The scaffolds exhibited lower weight loss (up to 7%, 15 days) after enzymatic degradation due to the combined effects of genipin crosslinking and β-TCP incorporation. In vitro studies showed that the constructs supported ATDC5 chondrocyte-like cells and MC3T3 osteoblast-like cells in duo culture conditions, providing a suitable environment for cell adhesion and proliferation for up to 14 days. Overall, the physicochemical properties and biological results of the developed chitosan/β-tricalcium phosphate/silk fibroin bilayered scaffolds suggest that they may be potential candidates for osteochondral tissue strategies.

Silk is called the “Queen” of “fibers” due to its eco-friendly nature, robust mechanical properties, biocompatibility, heat conductivity, durability, luster, and tunable biodegradability. Consequently, silk has been widely used to fabricate matrices for many applications, including tissue engineering (bone, cartilage, skin regeneration), controlled drug delivery devices, and cancer therapy (in vitro models). Silk proteins fibroin and sericin-based architectures have been produced using electrospinning, solvent casting, freeze-drying, three-dimensional printing, and physical and chemical crosslinking to address the different challenges involved in these applications. This chapter discusses, in brief, the different types of mulberry and nonmulberry silkworm species and the properties of fibroin and sericin. Technological advances involving the utilization of silk-based biomaterials are addressed.

Silk fibroin (SF) is a well-known natural protein with considerable potential to develop high-value materials for biomedical applications due to its intrinsic features, such as availability, versatility, and biocompatibility. In recent investigations, ionic liquids (ILs) have attracted attention as green solvents for tuning SF-based biomaterials. Like traditional solvents, ILs can be used as a solvent to process SF in different shapes, such as films, hydrogels, sponges, and microparticles. The resulting architectures can be applied to regenerate skin, bone, and cartilage and act as drug-delivery systems. Additionally, the IL platform has demonstrated its potential for creating SF-based therapeutic platforms with enhanced environmental and biological features. This chapter provides an up-to-date review of the SF-based matrices produced using ILs, the strategies used for processing, main properties, biomedical applications, and future perspectives.

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.

Acmella oleracea (L.) is a plant popularly known as jambu in the Brazilian Amazon. This species has several biological properties, such as anaesthetic, antioxidant and anti-inflammatory activities, among others. However, there is limited information on its anticancer activity. In this context, this study aims to evaluate the effects of the hydroethanolic extract of jambu and its active compound (spilanthol) on gastric cancer cells. Hydroethanolic jambu inflorescence extract was obtained, and spilanthol was isolated by HPLC. Biological cytotoxicity assays were determined using MTT tests. In addition, an in silico study using molecular docking evaluated the inhibitory properties of spilanthol against JAK1 and JAK2 proteins. The results showed that the hydroethanolic extract and the isolated compound spilanthol exhibited cytotoxicity against cancer cells. Molecular docking revealed that spilanthol has inhibitory potential for JAK1 and JAK2 proteins. Thus, extract of jambu and spilanthol can be a possible candidate for the treatment of gastric carcinoma.

Two Amazonian fungi strains - Aspergillus sp. A1C2-06 and Talaromyces verruculosus A1C2-05 - were studied about their potential as cellulase producers and theis applications in the saccharification of sugarcane bagasse and babassu lignocellulosic biomass. For the cellulase production was studied the influence of cultivation pa-rameters during the solid-state fermentation. The best initial pH were 3,0 and 7,0 for T. verruculosus and Aspergillus sp., respectively, and the optimum temperature was 35 degrees C for both strains. The ideal Mandel' solution volume was 7,5 ml and 10,0 ml for T. verruculosus and Aspergillus sp., respectively. The optimal conditions during the hydrolysis of filter paper cellulose were determined, being 2,8 the optimal pH for both cellulases and the optimal temperature were 50 degrees C and 60 degrees C forAspergillus sp and T. verruculosus, respectively. The cellulases from both Aspergillus sp and T. verruculosus were capable of hydrolyzing the lignocellulosic biomasses but in different degree of saccharification. The saccharification degree for both pretreated biomasses reached 80% when cel-lulases from T. verruculosus were applied for 72h, while the untreated biomasses reached only 60% for babassu and 50% for sugarcane bagasse, indicating that the removal of lignin has an important role in the process of biomass saccharification.

The potential of essential oils (EOs) has been proven for several solutions in the agricultural sector, among others, which makes the exploration of this matrix an ongoing activity. From this perspective, this work investigated essential oils from medicinal and condimentary species commonly used in the Amazon region for the control of Eragrostis plana Nees, an invasive species with a great impact on forage production. The EOs of Copaifera sp., Bixa orellana L., Piper tuberculatum Jacq., Chenopodium ambrosioides L. and Ocimum gratissimum L. were obtained via hydrodistillation, characterized via GC-MS and used in the preparation of solutions that were applied in vitro tests E. plana. All EOs tested affected the germination and initial growth of E. plana, but that of C. ambrosioides was the most efficient in inhibiting emergence, reaching a reduction greater than 97 % in accumulated germination when applied at a concentration of 0.1 %, followed by the EO of O. gratissimum, with inhibition of almost 75 % at the same concentration. The other oils, although in higher concentrations, also showed an interesting potential for controlling the germination of this invasive species. Similarly, a significant and more pronounced reduction in the initial growth of seedlings was observed in exposure to the EO of C. ambrosioides, which showed a major volatile composition characterized by the identification of ascaridol (5.75 %), glycosylated ascaridol (10.58 %), linalool acetate (11.26 %) and dihydrocitronellol acetate (19.53 %). These results, although initial, validate the efficiency of essential oils as promising biological products for application in the agricultural sector. (c) 2023 SAAB. Published by Elsevier B.V. All rights reserved.

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.

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.

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.

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.

Microencapsulating pancreatic islets in immunoprotective alginate hydrogels is a promising strategy for treatment of type 1 diabetes. However, this strategy is limited by inflammation and hypoxia mediated oxidative stress, due to encapsulation and the hydrogel itself, leading to impaired insulin secretion and limited short and long term cell survival. Herein, the antioxidant effect of fucoidan, an algae derived polysaccharide, on beta cells, and its positive effects on encapsulated beta cell viability and function is presented. Fucoidan from Fucus vesiculosus (FF) exhibits a high total antioxidant capacity, and free radical scavenging activity, and is able to significantly alleviate intracellular oxidative stress in rat insolinoma beta cells (INS1E). In addition, FF significantly increases insulin secretion in a dose‐ and time‐dependent manner. When FF is incorporated in ultrapure alginate used for microencapsulation of primary rat islets, both viability and glucose responsiveness of rat islets in these socalled Fucogel microcapsules (Fucocaps) are found to be significantly higher compared to islets encapsulated in alginate alone. Similar results are obtained with INS1E pseudoislets and neonatal pig islets. Fucocaps can provide a redox‐modulatory niche and an immune barrier for islets and beta cells in the same time leading to significantly improved survival and endocrine function by mitigating oxidative stress.

Vegetable oils have been suggested in polymer science as an environmentally friendly feedstock existing in abundance in nature, with worldwide availability and low cost. Although they have been widely explored as building blocks for polymers synthesis, their functional roles as owners of potent biomolecules are less unexplored. Their ancient biomolecules support natural biological roles such as antioxidant, antibacterial, anti-inflammatory, and anti-tumor properties, which are considered a great promise for biomedical proposes. This comprehensive review provides an overview of grape, soybean, castor, sesame, olive vegetable oils where their native anti-inflammatory, anti-tumor, antioxidant, and antibacterial biological compounds bring health benefits that can be translated to the biomedical field. These plant oils are considered the most relevant for the molecular design of functional and high-performance biomaterials that can contribute to the reduction of carbon footprint. The representative examples of vegetable oil-derived biomaterials, their main composition, shape, and the processing technology will be covered and innovative strategies toward the development of new multifunctional polymeric materials for pharmacological patches, wound healing devices, drug carriers, and scaffolds for tissue engineering applications will be discussed.

The combination of natural resources with biologically active biocompatible ionic liquids (Bio-IL) is pre-sented as a combinatorial approach for developing tools to manage inflammatory diseases. Innovative biomedical solutions were constructed combining silk fibroin (SF) and Ch[Gallate], a Bio-IL with antioxidant and anti-inflammatory features, as freeze-dried 3D-based sponges. An evaluation of the effect of the Ch[Gallate] concentration ( <= 3% w/v) on the SF/Ch[Gallate] sponges was studied. Structural changes observed on the sponges revealed that the Ch[Gallate] presence positively affected the beta-sheet formation while not influencing the silk native structure, which was suggested by the FTIR and solid-state NMR results, respectively. Also, it was possible to modulate their mechanical properties, antioxidant activity and stability/degradation in an aqueous environment, by changing the Ch[Gallate] concentration. The architectures showed high water uptake ability and a weight loss that follows the controlled Ch[Gallate] release rate studied for 7 days. Furthermore, the sponges supported human adipose stem cells growth and prolif-eration, up to 7 days. TNF-alpha, IL-6 (pro-inflammatory) and IL-10 (anti-inflammatory) release quantification from a human monocyte cell line revealed a decrease in the pro-inflammatory cytokines concentrations in samples containing Ch[Gallate]. These outcomes encourage the use of the developed architectures as tissue engineering solutions, potentially targeting inflammation processes. Statement of Significance Combining natural resources with active biocompatible ionic liquids (Bio-IL) is herein presented as a combinatorial approach for the development of tools to manage inflammatory diseases. We propose using silk fibroin (SF), a natural protein, with cholinium gallate, a Bio-IL, with antioxidant and anti-inflammatory properties, to construct 3D-porous sponges through a sustainable methodology. The mor-phological features, swelling, and stability of the architectures were controlled by Bio-IL content in the matrices. The sponges were able to support human adipose stem cells growth and proliferation, and their therapeutic effect was proved by the blockage of TNF-alpha from activated and differentiated THP-1 mono-cytes. We believe that these bio-friendly and bioactive SF/Bio-IL-based sponges are effective for targeting pathologies with associated inflammatory processes. (C) 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.