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Microalgae are microorganisms that are rich in bioactive compounds, including pigments, proteins, lipids, and polysaccharides. These compounds can be utilized for a number of biomedical purposes, including drug delivery, wound healing, and tissue engineering. Nevertheless, encapsulating microalgae cells and microalgae bioactive metabolites is vital to protect them and prevent premature degradation. This also enables the development of intelligent controlled release strategies for the bioactive compounds. This review outlines the most employed encapsulation techniques for microalgae, with a particular focus on their biomedical applications. These include ionic gelation, oil-in-water emulsions, and spray drying. Such techniques have been widely explored, due to their ability to protect sensitive compounds from degradation, enhance their stability, extend their shelf life, mask undesirable tastes or odours, control the release of bioactive compounds, and enable targeted delivery to specific sites within the body or environment. Moreover, a patent landscape analysis is also provided, allowing an overview of the microalgae encapsulation technology development applied to a variety of fields, including pharmaceuticals, cosmetics, food, and agriculture., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Bone is a mineralized tissue with the intrinsic capacity for constant remodeling. Rapid prototyping techniques, using biomaterials that mimic the bone native matrix, have been used to develop osteoinductive and osteogenic personalized 3D structures, which can be further combined with drug delivery and phototherapy. Herein, a Fab@Home 3D Plotter printer was used to promote the layer-by-layer deposition of a composite mixture of gelatin, chitosan, tricalcium phosphate, and reduced graphene oxide (rGO). The phototherapeutic potential of the new NIR-responsive 3D_rGO scaffolds was assessed by comparing scaffolds with different rGO concentrations (1, 2, and 4 mg/mL). The data obtained show that the rGO incorporation confers to the scaffolds the capacity to interact with NIR light and induce a hyperthermy effect, with a maximum temperature increase of 16.7 °C after under NIR irradiation (10 min). Also, the increase in the rGO content improved the hydrophilicity and mechanical resistance of the scaffolds, particularly in the 3D_rGO4. Furthermore, the rGO could confer an NIR-triggered antibacterial effect to the 3D scaffolds, without compromising the osteoblasts' proliferation and viability. In general, the obtained data support the development of 3D_rGO for being applied as temporary scaffolds supporting the new bone tissue formation and avoiding the establishment of bacterial infections., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Asymmetric wound dressings have captured researchers' attention due to their ability to reproduce the structural and functional properties of the skin layers. Furthermore, recent studies also report the benefits of using near-infrared (NIR) radiation-activated photothermal therapies in treating infections and chronic wounds. Herein, a chitosan (CS) and reduced graphene oxide (rGO) hydrogel (CS_rGO) was combined with a polycaprolactone (PCL) and cellulose acetate (CA) electrospun membrane (PCL_CA) to create a new NIR-responsive asymmetric wound dressing. The rGO incorporation in the hydrogel increased the NIR absorption capacity and allowed a mild hyperthermy effect, a temperature increase of 12.4 °C when irradiated with a NIR laser. Moreover, the PCL_CA membrane presented a low porosity and hydrophobic nature, whereas the CS_rGO hydrogel showed the ability to provide a moist environment, prevent exudate accumulation and allow gaseous exchanges. Furthermore, the in vitro data demonstrate the capacity of the asymmetric structure to act as a barrier against bacteria penetration as well as mediating a NIR-triggered antibacterial effect. Additionally, human fibroblasts were able to adhere and proliferate in the CS_rGO hydrogel, even under NIR laser irradiation, presenting cellular viabilities superior to 90 %. Altogether, our data support the application of the NIR-responsive asymmetric wound dressings for skin regeneration., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mariana F. P. Graca reports financial support was provided by Foundation for Science and Technology. Bruna L. Melo reports financial support was provided by Foundation for Science and Technology. Rita Lima-Sousa reports financial support was provided by Foundation for Science and Technology. Andre F. Moreira reports financial support was provided by Foundation for Science and Technology. Ilidio J. Correia reports financial support was provided by Foundation for Science and Technology. Andre F. Moreira reports financial support was provided by Fundo Europeu de Desenvolvimento Regional. Ilidio J. Correia reports financial support was provided by Fundo Europeu de Desenvolvimento Regional., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

The high near infrared (NIR) absorption displayed by reduced graphene oxide (rGO) nanostructures renders them a great potential for application in cancer photothermal therapy. However, the production of this material often relies on the use of hydrazine as a reductant, leading to poor biocompatibility and environmental-related issues. In addition, to improve rGO colloidal stability, this material has been functionalized with poly(ethylene glycol). However, recent studies have reported the immunogenicity of poly(ethylene glycol)-based coatings. In this work, the production of rGO, by using dopamine as the reducing agent, was optimized considering the size distribution and NIR absorption of the attained materials. The obtained results unveiled that the rGO produced by using a 1:5 graphene oxide:dopamine weight ratio and a reaction time of 4 h (termed as DOPA-rGO) displayed the highest NIR absorption while retaining its nanometric size distribution. Subsequently, the DOPA-rGO was functionalized with thiol-terminated poly(2-ethyl-2-oxazoline) (P-DOPA-rGO), revealing suitable physicochemical features, colloidal stability and cytocompatibility. When irradiated with NIR light, the P-DOPA-rGO could produce a temperature increase (ΔT) of 36 °C (75 μg/mL; 808 nm, 1.7 W/cm 2 , 5 min). The photothermal therapy mediated by P-DOPA-rGO was capable of ablating breast cancer cells monolayers (viability < 3%) and could reduce heterotypic breast cancer spheroids' viability to just 30%. Overall, P-DOPA-rGO holds a great potential for application in breast cancer photothermal therapy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Combinatorial therapies based on the simultaneous administration of multiple drugs can lead to synergistic effects, increasing the efficacy of the cancer therapy. However, it is crucial to develop new delivery systems that can increase the drugs' therapeutic selectivity and efficacy. Gold core silica shell (AuMSS) nanoparticles present physicochemical properties that allow their simultaneous application as drug delivery and imaging agents. Herein, poly(ethylene glycol) was modified with 4-methoxybenzamide and 3-(triethoxysilyl)propyl isocyanate (TPANIS) to create a novel surface functionalization capable of improving the colloidal stability and specificity of AuMSS nanospheres towards cancer cells. Moreover, a dual drug combination based on Doxorubicin (DOX) and Acridine orange (AO) was characterized and administered using the AuMSS-TPANIS nanospheres. The obtained results show that the DOX:AO drug combination can mediate a synergistic therapeutic effect in both HeLa and MCF-7 cells, particularly at the 2:1, 1:1, and 1:2 ratios. Additionally, the TPANIS functionalization increased the AuMSS nanospheres colloidal stability and selectivity towards MCF-7 cancer cells (overexpressing sigma receptors). Such also resulted in an enhanced cytotoxic effect against MCF-7 cells when administering the DOX:AO drug combination with the AuMSS-TPANIS nanospheres. Overall, the obtained results confirm the therapeutic potential of the DOX:AO drug combination as well as the targeting capacity of AuMSS-TPANIS, supporting its application in the cancer-targeted combinatorial chemotherapy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The plasmonic photothermal properties of gold nanoparticles have been widely explored in the biomedical field to mediate a photothermal effect in response to the irradiation with an external light source. Particularly, in cancer therapy, the physicochemical properties of gold-based nanomaterials allow them to efficiently accumulate in the tumor tissue and then mediate the light-triggered thermal destruction of cancer cells with high spatial-temporal control. Nevertheless, the gold nanomaterials can be produced with different shapes, sizes, and organizations such as nanospheres, nanorods, nanocages, nanoshells, and nanoclusters. These gold nanostructures will present different plasmonic photothermal properties that can impact cancer thermal ablation. This review analyses the application of gold-based nanomaterials in cancer photothermal therapy, emphasizing the main parameters that affect its light-to-heat conversion efficiency and consequently the photothermal potential. The different shapes/organizations (clusters, shells, rods, stars, cages) of gold nanomaterials and the parameters that can be fine-tuned to improve the photothermal capacity are presented. Moreover, the gold nanostructures combination with other materials (e.g. silica, graphene, and iron oxide) or small molecules (e.g. indocyanine green and IR780) to improve the nanomaterials photothermal capacity is also overviewed., Competing Interests: Declaration of Competing Interest The authors declare no financial or commercial conflict of interest., (Copyright © 2020. Published by Elsevier Ltd.)

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., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Gold-core mesoporous silica shell (AuMSS) nanorods unique physicochemical properties makes them versatile and promising nanomedicines for cancer photothermal therapy. Nevertheless, these nanomaterials present a reduced half-life in the blood and poor specificity towards the tumor tissue. Herein, d-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) and Hyaluronic Acid (HA) were combined for the first time to improve the AuMSS nanorods biological performance. The obtained results revealed that AuMSS surface functionalization induced the surface charge neutralization, from -28 ± 10 mV to -3 ± 5 mV and -10 ± 4 mV for AuMSS-TPGS-HA (1:1) and (4:1) formulations, without impacting on nanomaterials' photothermal capacity. Moreover, the AuMSS functionalization improved the nanomaterials hemocompatibility and selectivity towards the cancer cells, particularly in the AuMSS-TPGS-HA (4:1) formulation. Furthermore, both formulations were able to mediate an on-demand photothermal effect, that induced the HeLa cancer cells death, confirming its potential for being applied as targeted multifunctional theragnostic nanomedicines., Competing Interests: Declaration of Competing Interest There are no conflicts to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Macroscale delivery systems that can be locally implanted on the tumor tissue as well as avoid all the complications associated to the systemic delivery of therapeutics have captured researchers' attention, in recent years. Particularly, the microneedle-based devices can be used to efficiently deliver both small and macro-molecules, like chemotherapeutics, proteins, and genetic material, along with nanoparticle-based anticancer therapies. Such capacity prompted the application of microneedle devices for the development of new anticancer vaccines that can permeate the tumor tissue and simultaneously improve the effectiveness of therapeutic agents. Based on the promising results demonstrated by the microneedle systems in the local administration of anticancer therapeutics, this review summarizes the different microneedle formulations developed up to now aimed for application on cancer therapy (mphasizing those produced with polymers). Additionally, the microneedles' general properties, type of therapeutic approach and its main advantages are also highlighted., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

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&#95;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&#95;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., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Cancer is one of the major world public health problems and the currently available treatments are nonspecific and ineffective. This reality highlights the importance of developing novel therapeutic approaches. In this field, multifunctional nanomedicines have the potential to revolutionize the currently available treatments. These unique nanodevices can simultaneously act as therapeutic and imaging agents allowing the real-time monitoring of the nanoparticles biodistribution and the treatment outcome. Among the different nanoparticles, the gold-core silica shell (AuMSS) nanoparticles advantageous physicochemical and biological properties make them promising nanoplatforms for cancer therapy. Nevertheless, their successful application as an effective cancer nanomedicine is limited by the unfavorable pharmacokinetics and uncontrolled release of the therapeutic payloads. Herein, a new polymeric coating for AuMSS nanospheres was developed by combining different ratios (25/75, 50/50 and 75/25) of two materials, Poly-2-ethyl-2-oxazoline (PEOZ) and β-cyclodextrin (β-CD). The surface functionalization of AuMSS nanospheres led to a size increase and to the neutralization of the surface charge. On the other side, the nanoparticles biological performance was improved. The coated AuMSS nanospheres showed an increased cytocompatibility and internalization rate by the HeLa cancer cells. Overall, the obtained data confirm the successful modification of the AuMSS nanospheres with PEOZ and β-CD as well as their promising properties for being applied in cancer therapy., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The wound healing process involves highly complex and dynamic events that allow the re-establishment of skin's structural integrity. To further improve or to overcome the drawbacks associated with this process, researchers have been focused on the development of new therapeutics. Among them, asymmetric membranes are currently one of the most promising approaches to be used in wound healing due to its structural similarities with the epidermal and dermal layers of the native skin. The outer layer of asymmetric membranes provides a barrier that protects the wound from external damages (e.g. microorganisms and chemical agents), whereas the interior porous layer acts as template for supporting cell adhesion, migration and proliferation. Among the different materials used to produce these distinct layers, the chitosan arises as one of the preeminent materials due to its inherent biocompatibility, antibacterial, hemostatic, and healing properties. Therefore, in this review, it is provided an overview of the different chitosan-based asymmetric membranes developed for wound dressing applications. Further, the chitosan modifications to enhance its bioactivity as well as the asymmetric membranes general properties and production techniques are also described., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Nowadays, wound dressings with improved properties are under development and among them, asymmetric membranes have gained an increasing interest due to their two-layered structure that mimic both the epidermis and dermis layers of the skin. Herein, a new asymmetric membrane was produced using the electrospinning technique. The top layer was produced with silk fibroin (SF) and poly(caprolactone) to reproduce the dense nature and waterproof ability of the epidermis. On the other hand, the dermis-like bottom layer was manufactured with SF and hyaluronic acid loaded with an herbal drug (thymol (THY)). All the data gathered showed that the produced electrospun asymmetric membrane exhibited the porosity, wettability, and mechanical properties suitable for the healing process. Further, the in vitro data also demonstrated that the human fibroblast is able to adhere and spread at the membranes' surface, thus confirming their biocompatibility. Moreover, the incorporation of THY into the bottom layer of the membrane, improved its antioxidant and antibacterial properties. Overall, the obtained results demonstrate the appropriateness of the produced membrane for wound healing applications., (Copyright © 2018. Published by Elsevier B.V.)

Drug-DNA combination therapies are receiving an ever growing focus due to their potential for improving cancer treatment. However, such approaches are still limited by the lack of multipurpose delivery systems that encapsulate drugs and condense DNA simultaneously. In this study, we describe the successful formulation of gas-generating pH-responsive D-α-tocopherol PEG succinate-poly(D,L-lactic-co-glycolic acid) (TPGS-PLGA) hollow microspheres loaded with both Doxorubicin (Dox) and minicircle DNA (mcDNA) nanoparticles as a strategy to co-deliver these therapeutics. For this study mcDNA vectors were chosen due to their increased therapeutic efficiency in comparison to standard plasmid DNA. The results demonstrate that TPGS-PLGA microcarriers can encapsulate Dox and chitosan nanoparticles completely condense mcDNA. The loading of mcDNA-nanoparticles into microspheres was confirmed by 3D confocal microscopy and co-localization analysis. The resulting TPGS-PLGA-Dox-mcDNA nanoparticle-in-microsphere hybrid carriers exhibit a well-defined spherical shape and neutral surface charge. Microcarriers incubation in acidic pH produced a gas-mediated Dox release, corroborating the microcarriers stimuli-responsive character. Also, the dual-loaded TPGS-PLGA particles achieved 5.2-fold higher cellular internalization in comparison with non-pegylated microspheres. This increased intracellular concentration resulted in a higher cytotoxic effect. Successful transgene expression was obtained after nanoparticle-mcDNA co-delivery in the microspheres. Overall these findings support the concept of using nanoparticle-microsphere multipart systems to achieve efficient co-delivery of various drug-mcDNA combinations., (Copyright © 2015 Elsevier B.V. All rights reserved.)