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]14â) 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 2â 5μm (SEM), were further dispersed into CHT/VCO (virgin coconut oil) emulsion solutions that were casted into molds and dried at 37 â ¦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.The authors would like to thank the contributions to this research from the project “TERM RES Hub–Scientific Infrastructure for Tissue Engineering and Regenerative Medicine”, reference PINFRA/22190/2016 (Norte-01-0145-FEDER-022190), funded by the Portuguese National Science Foundation (FCT) in cooperation with the Northern Portugal Regional Coordination and Development Commission (CCDR-N), for providing relevant lab facilities, state-of-the art equipment and highly qualified human resources

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.FCT (JMG, PD/BD/135247/2017 and LCR, SFRH/BPD/93697/2013). This work was also financially supported by a PhD programme in Advanced Therapies for Health (PATH) (PD/00169/2013); FCT R&D&I projects with references PTDC/BII‐BIO/31570/2017, PTDC/CTM‐CTM/29813/2017 and PTDC/CTM‐BIO/4706/2014‐(POCI‐01‐0145‐ FEDER‐016716) and R&D&I Structured Projects with reference NORTE‐01‐0145‐FDER‐00002

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.The authors especially acknowledge the financial support from the Portuguese FCT (grants CEECIND/01306/2018, SFRH/BPD/93697/2013, and SFRH/BPD/85790/2012). This work was also financially supported by the FCT R&D&I project, with reference PTDC/BII-BIO/31570/2017, and the R&D&I Structured Projects, with reference NORTE-01-0145-FDER-000021. We also acknowledge the financial support from São Paulo Research Foundation (FAPESP) in Brasil through projects 2015/25406-5 and 2021/12071-6, and for the postdoctoral grant to D.G.V., 2019/12665-3. The project 2018/08045-7 is part of a bilateral agreement between FAPESP and the FCT (Portugal), involving the project Nature4Health

Acemannan-based films: an improved approach envisioning biomedical applications

In the last years, a renewed interest in natural compounds from medicinal plants uses arose due totheir intrinsic bioactive properties. Acemannan(ACE), aloe vera leaves the main polysaccharide, iscytocompatible, wound healing inducer, antibacterial and immunomodulator. Thus, its associationwith natural polymers as chitosan(CHT)and alginate(ALG)can result in strong synergistic effects,due to the interactions established between the polymers leading to mixed junction zones formation.In this work, ACE-basedfilms were prepared through the combination of ACE with CHT or ALG.Films were characterized to evaluate their physical features and chemical composition. Thefindingsrevealed that the presence of calcium ions into ACE composition induced an effective gelation withALG and a polymeric arrangement with CHT. Moreover, an increase of ACE ratio in ALG/ACE leadto more resistant and stable structures. Thefindings obtained suggest that ACE-basedfilms are goodcandidates to be used as bioactive platforms.L.C. Rodrigues specially acknowledge financial support from Portuguese FCT (SFRH/BPD/93697/2013). This work is also financially supported by the FCT R&D&I projects with references SFRH/BPD/93697/2013- (POCI-01–0145-FEDER-016716) and R&D&I Structured Projects with reference NORTE-01-0145-FDER000021

Biopolymer membranes in tissue engineering

In tissue engineering and regenerative medicine, the combination of biomaterials, cells, and bioactive molecules is the key to promote tissue regeneration or even to create therapeutic systems. The use of natural biomacromolecules in the processing of membranes has been extensively applied in association with traditional processing techniques. The resulting structures present multiple mechanical and biological features that allow their application as wound dressings for skin regeneration, drug delivery systems, and bone regeneration supports. This chapter provides an up-to-date review of the most promising natural biopolymers processed as membranes, focusing on polysaccharides, proteins and their combinations, strategies for processing, and their applications in the tissue-engineering field

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.The authors especially acknowledge financial support from Portuguese Fundação para a Ciência e Tecnologia (FCT) (PD/BD/135247/2017, SFRH/BPD/93697/2013 and CEECIND/01306/2018). This work is also financially supported by PhD Programme in Advanced Therapies for Health (PATH) (PD/00169/2013), FCT R&D&I projects with references PTDC/BII-BIO/31570/2017, PTDC/CTM-CTM/29813/2017, and R&D&I Structured Projects with reference NORTE-01-0145-FDER000021

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 (smax)), 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.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The research leading to these results has received funding from the Portuguese Foundation for Science and Technology (FCT) by PTDC/CTM-BIO/4706/2014 and SFRH/BPD/ 93697/2013 and from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement number REGPOT-CT2012- 316331-POLARIS.info:eu-repo/semantics/publishedVersio

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.L.C. Rodrigues especially acknowledges financial support from Portuguese FCT (SFRH/BPD/93697/2013). This work is also financially supported by the FCT R&D&I projects with references PTDC/CTM-BIO/ 4706/2014-(POCI-01-0145-FEDER-016716), PTDC/CTM-CTM/29813/ 2017-(POCI-01-0145-FEDER-029813), PTDC/BII-BIO/31570/2017, and R&D&I Structured Projects with reference NORTE-01-0145- FEDER-000021

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 Youngâ 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.This research was funded by the Portuguese Foundation for Science and Technology (FCT), under the scope of individual fellowships/contracts (SFRH/BD/112139/2015, and SFRH/BPD/93697/ 2013, SFRH/BPD/85790/2012 and CEECIND/01306/2018) and research projects (PTDC/CTMCTM//29813/2017 and PTDC/BII-BIO/31570/2017); by the Northern Portugal Regional Operational Programme (NORTE 2020), under the scope of Structured Projects NORTE-01-0145-FEDER-000021 and NORTE-01-0145-FEDER-000023; and by European Union Transborder Cooperation Program Interreg España-Portugal 2014-2020 (POCTEP), under the scope of project 0302_CVMAR_I_1_P

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, of- fering exclusive strategies for precise pharmacological screenings in osteoarthritis (OA). Synovial inflam- mation plays a crucial role in OAâ s early stage and progression, characterized by the increased of the syn- ovial 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), aceman- nan (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 distribu- tion, 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- αand IL-6) and mediators (GM-CSF), re- leased by the cultured cells. Moreover, incorporating the biocompatible ionic liquid into the system sig- nificantly 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.The authors especially acknowledge financial support from Portuguese FCT (PD/BD/135247/2017, SFRH/BPD/93697/2013, CEECINST/00018/2021 and CEECIND/04687/2017). This work is also financially supported by PhD programme in Advanced Thera pies for Health (PATH) (PD/00169/2013), FCT R&D&I project with reference PTDC/BII-BIO/31570/2017. The authors would like to thank the contributions to this research from the project “TERMRES Hub – Scientific Infrastructure for Tissue Engineering and Regenerative Medicine”, reference PINFRA/22190/2016 (Norte-01-0145-FEDER-022190), funded by the Portuguese National Science Foundation (FCT) in cooperation with the Northern Portugal Regional Coordination and Development Commission (CCDR-N), for providing relevant lab facilities, state-of-the-art equipment and highly qualified human resource