[en] Al-free glasses of general composition 0.340SiO₂:0.300ZnO:(0.250-a-b)CaO:aSrO:bMgO:0.050Na₂O:0.060P₂O₅ (a, b = 0.000 or 0.125) were synthesized by melt quenching and their ability to form glass-ionomer cements was evaluated using poly(acrylic acid) and water. We evaluated the influence of the poly(acrylic acid) molecular weight and glass particle size in the cement mechanical performance. Higher compressive strength (25 ± 5 MPa) and higher compressive elastic modulus (492 ± 17 MPa) were achieved with a poly(acrylic acid) of 50 kDa and glass particle sizes between 63 and 125 μm. Cements prepared with glass formulation a = 0.125 and b = 0.000 were analyzed after immersion in simulated body fluid; they presented a surface morphology consistent with a calcium phosphate coating and a Ca/P ratio of 1.55 (similar to calcium-deficient hydroxyapatite). Addition of starch to the cement formulation induced partial degradability after 8 weeks of immersion in phosphate buffer saline containing α-amylase. Micro-computed tomography analysis revealed that the inclusion of starch increased the cement porosity from 35% to 42%. We were able to produce partially degradable Al-free glass-ionomer bone cements with mechanical performance, bioactivity and biodegradability suitable to be applied on non-load bearing sites and with the appropriate physical characteristics for osteointegration upon partial degradation. Zn release studies (concentrations between 413 μM and 887 μM) evidenced the necessity to tune the cement formulations to reduce the Zn concentration in the surrounding environment. Highlights: ► We developed partially degradable, bioactive, Al-free glass-ionomer cements (GICs). ► Enhanced mechanical behavior was achieved using 63–125 μm glass particle size range. ► The highest mechanical resistance was obtained using poly(acrylic acid) of 50 kDa. ► Biodegradation was successfully tuned to start 8 weeks after GIC preparation. ► Zn release should be tuned to the non-cytotoxic levels

[en] The objective of this study was to investigate the influence of silk fibroin and oxidized starch conjugation on the enzymatic degradation behavior and the cytocompatability of chitosan based biomaterials. The tensile stress of conjugate membranes, which was at 50 Megapascal (MPa) for the lowest fibroin and starch composition (10 weight percent (wt.%)), was decreased significantly with the increased content of fibroin and starch. The weight loss of conjugates in α-amylase was more notable when the starch concentration was the highest at 30 wt.%. The conjugates were resistant to the degradation by protease and lysozyme except for the conjugates with the lowest starch concentration. After 10 days of cell culture, the proliferation of osteoblast-like cells (SaOS-2) was stimulated significantly by higher fibroin compositions and the DNA synthesis on the conjugate with the highest fibroin (30 wt.%) was about two times more compared to the native chitosan. The light microscopy and the image analysis results showed that the cell area and the lengths were decreased significantly with higher fibroin/chitosan ratio. The study proved that the conjugation of fibroin and starch with the chitosan based biomaterials by the use of non-toxic reductive alkylation crosslinking significantly improved the cytocompatibility and modulated the biodegradation, respectively. - Highlights: ► Silk fibroin, starch and chitosan conjugates were prepared by reductive alkylation. ► The enzymatic biodegradation and the cytocompatibility of conjugates were tested. ► The conjugate with 30% starch composition was degraded by α-amylase significantly. ► Higher starch composition in conjugates prevented protease and lysozyme degradation. ► Fibroin incorporation effectively increased the cell proliferation of conjugates.

[en] In the last years, a renewed interest in natural compounds from medicinal plants uses arose due to their intrinsic bioactive properties. Acemannan (ACE), aloe vera leaves the main polysaccharide, is cytocompatible, wound healing inducer, antibacterial and immunomodulator. Thus, its association with 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-based films were prepared through the combination of ACE with CHT or ALG. Films were characterized to evaluate their physical features and chemical composition. The findings revealed that the presence of calcium ions into ACE composition induced an effective gelation with ALG and a polymeric arrangement with CHT. Moreover, an increase of ACE ratio in ALG/ACE lead to more resistant and stable structures. The findings obtained suggest that ACE-based films are good candidates to be used as bioactive platforms. (paper)

[en] In this work, we focused on the potential of bioceramics from different marine sponges—namely Petrosia ficiformis , Agelas oroides and Chondrosia reniformis— for novel biomedical/industrial applications. The bioceramics from these sponges were obtained after calcination at 750 °C for 6 h in a furnace. The morphological characteristics were evaluated by scanning electron microscopy (SEM). The in vitro bioactivity of the bioceramics was evaluated in simulated body fluid (SBF) after 14 and 21 d. Observation of the bioceramics by SEM after immersion in SBF solution, coupled with spectroscopic elemental analysis (EDS), showed that the surface morphology was consistent with a calcium-phosphate (Ca/P) coating, similar to hydroxyapatite crystals (HA). Evaluation of the characteristic peaks of Ca/P crystals by Fourier transform infrared spectroscopy and x-ray diffraction further confirmed the existence of HA. Cytotoxicity studies were carried out with the different ceramics and these were compared with a commercially available Bioglass^®. In vitro tests demonstrated that marine bioceramics from these sponges are non-cytotoxic and have the potential to be used as substitutes for synthetic Bioglass^®. (paper)

[en] Kefiran from kefir grains, an exopolysaccharide (EPS) produced by lactic acid bacteria (LAB), has received an increasing interest because of its safe status. This natural biopolymer is a water-soluble glucogalactan with probed health-promoting properties. However, its biological performance has yet to be completely recognized and properly exploited. This research was carried out to evaluate the in vitro antioxidant and the in vitro anti-inflammatory properties of Kefiran biopolymer. Regarding antioxidant activity, the results demonstrated that the Kefiran extract possessed the strongest reducing power and superoxide radical scavenging, over hyaluronic acid (HA, gold standard viscosupplementation treatment). This exopolysaccharide showed a distinct antioxidant performance in the majority of in vitro working mechanisms of antioxidant activity comparing to HA. Moreover, Kefiran presented an interesting capacity to scavenge nitric oxide radical comparing to the gold standard that did not present any potency. Finally, the cytotoxic effects of Kefiran extracts on hASCs were also performed and demonstrated no cytotoxic response, ability to improve cellular function of hASCs. This study demonstrated that Kefiran represented a great scavenger for reactive oxygen and nitrogen species and showed also that it could be an excellent candidate to promote tissue repair and regeneration.

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[en] Oral administration of drugs presents important limitations, which are frequently not granted the importance that they really have. For instance, hepatic metabolism means an important drug loss, while some patients have their ability to swell highly compromised (i.e. unconsciousness, cancer…). Sublingual placement of an accurate Pharmaceutical Dosage Form is an attractive alternative. This work explores the use of the β-chitosan membranes, from marine industry residues, composed with marine sediments for dual sublingual drug delivery. As proof of concept, the membranes were loaded with a hydrophilic (gentamicin) and a hydrophobic (dexamethasone) drug. The physico-chemical and morphological characterization indicated the successful incorporated of diatomaceous earth within the chitosan membranes. Drug delivery studies showed the potential of all formulations for the immediate release of hydrophilic drugs, while diatomaceous earth improved the loading and release of the hydrophobic drug. These results highlight the interest of the herein developed membranes for dual drug delivery.

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[en] The use of magnetic nanoparticles (MNPs) towards the musculoskeletal tissues has been the focus of many studies, regarding MNPs ability to promote and direct cellular stimulation and orient tissue responses. This is thought to be mainly achieved by mechano-responsive pathways, which can induce changes in cell behavior, including the processes of proliferation and differentiation, in response to external mechanical stimuli. Thus, the application of MNP-based strategies in tissue engineering may hold potential to propose novel solutions for cell therapy on bone and cartilage strategies to accomplish tissue regeneration. The present work aims at studying the influence of MNPs on the osteogenic and chondrogenic differentiation of human adipose derived stem cells (hASCs). MNPs were incorporated in hASCs and cultured in medium supplemented for osteogenic and chondrogenic differentiation. Cultures were maintained up to 28 days with/without an external magnetic stimulus provided by a magnetic bioreactor, to determine if the MNPs alone could affect the osteogenic or chondrogenic phenotype of the hASCs. Results indicate that the incorporation of MNPs does not negatively affect the viability nor the proliferation of hASCs. Furthermore, Alizarin Red staining evidences an enhancement in extracellular (ECM) mineralization under the influence of an external magnetic field. Although not as evident as for osteogenic differentiation, Toluidine blue and Safranin-O stainings also suggest the presence of a cartilage-like ECM with glycosaminoglycans and proteoglycans under the magnetic stimulus provided. Thus, MNPs incorporated in hASCs under the influence of an external magnetic field have the potential to induce differentiation towards the osteogenic and chondrogenic lineages. - Highlights: • Cellular viability was not negatively influenced by the nanoparticles. • Chondrogenic medium influences more the synthesis of cartilage-like ECM than MNPs. • Synergetic effect among osteogenic supplements, magnetic field and MNPs. • MNPs systems are promising candidates for bone and cartilage TE strategies

[en] Melanin function in the skin has been associated with pigmentation but other properties such as electrical conductance, photoprotection, and antioxidant and antimicrobial activity have also been recognized. Nonetheless, the use of melanin in a skin wound healing context has never been considered. In this sense, eumelanin particles with a typical round and nano-sized morphology and electrical conductivity of 2.09 × 10⁻⁸ S cm⁻¹ were extracted from the ink of Sepia officinalis . The ability of primary human keratinocytes (hKCs) to phagocyte eumelanin, which was then accumulated in cytosolic vesicles and nuclei surroundings, was demonstrated. Keratinocyte viability and maturation was not affected by eumelanin contact, but at eumelanin amounts higher than 0.1 mg l⁻¹ cell morphology was altered and cell proliferation was inhibited. A time and eumelanin amount-dependent reduction of reactive oxygen species (ROS) released by eumelanin-containing ultraviolet (UV)-irradiated keratinocytes was observed. Eumelanin-containing gellan gum (GG) spongy-like hydrogels allowed a sustained release of eumelanin in the range of 0.1 to 5 mg l⁻¹, which was shown in vitro to not be harmful to hKCs, and the absence of a strong host reaction after subcutaneous implantation in mice. Herein, we propose spongy-like hydrogels as sustained release matrices of S. officinalis eumelanin for predicting a beneficial role in skin wound healing through a direct effect over keratinocytes. (paper)

[en] This study reports on an original concept of additive manufacturing for the fabrication of tissue engineered constructs (TEC), offering the possibility of concomitantly manufacturing a customized scaffold and a bioreactor chamber to any size and shape. As a proof of concept towards the development of anatomically relevant TECs, this concept was utilized for the design and fabrication of a highly porous sheep tibia scaffold around which a bioreactor chamber of similar shape was simultaneously built. The morphology of the bioreactor/scaffold device was investigated by micro-computed tomography and scanning electron microscopy confirming the porous architecture of the sheep tibiae as opposed to the non-porous nature of the bioreactor chamber. Additionally, this study demonstrates that both the shape, as well as the inner architecture of the device can significantly impact the perfusion of fluid within the scaffold architecture. Indeed, fluid flow modelling revealed that this was of significant importance for controlling the nutrition flow pattern within the scaffold and the bioreactor chamber, avoiding the formation of stagnant flow regions detrimental for in vitro tissue development. The bioreactor/scaffold device was dynamically seeded with human primary osteoblasts and cultured under bi-directional perfusion for two and six weeks. Primary human osteoblasts were observed homogenously distributed throughout the scaffold, and were viable for the six week culture period. This work demonstrates a novel application for additive manufacturing in the development of scaffolds and bioreactors. Given the intrinsic flexibility of the additive manufacturing technology platform developed, more complex culture systems can be fabricated which would contribute to the advances in customized and patient-specific tissue engineering strategies for a wide range of applications. (paper)

[en] The potential of magnetically assisted strategies within the remit of cell-based therapies is increasing, creating new opportunities for biomedical platforms and in the field of tissue engineering and regenerative medicine. Among the magnetic elements approached for building magnetically responsive strategies, superparamagnetic iron oxide nanoparticles (SPIONs) represent tunable and precise tools whose properties can be modelled for detection, diagnosis, targeting and therapy purposes. The most investigated clinical role of SPIONs is as contrast imaging agents for tracking and monitoring cells and tissues. Nevertheless, magnetic detection also includes biomarker mapping, cell labelling and cell/drug targeting to monitor cell events and anticipate the disruption of homeostatic conditions and the progression of disease. Additionally, the isolation and screening techniques of cell subsets in heterogeneous populations or of proteins of interest have been explored in a magnetic sorting context. More recently, SPION-based technologies have been applied to stimulate cell differentiation and mechanotransduction processes and to transport genetic or drug cargo to study biological mechanisms and contribute to improved therapies. Magnetically based strategies significantly contribute to magnetic tissue engineering (magTE), in which magnetically responsive actuators built from magnetic labelled cells or magnetic functionalized systems can be remotely controlled and spatially manipulated upon the actuation of an external magnetic field for the delivery or target of TE solutions. SPION functionalities combined with magnetic responsiveness in multifactorial magnetically assisted platforms can revolutionize diagnosis and therapeutics, providing new diagnosis and theranostic tools, encouraging regenerative medicine approaches and having potential for more effective therapies. This review will address the contribution of SPION-based technologies as multifunctional tools in boosting magnetically assisted cell-based strategies to explore diagnostics and tracking solutions for the detection and analysis of pathologies, and to generate improved treatments and therapies, envisioning precise and customized answers for the management of numerous diseases. (review)