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Biomaterials capable of precisely controlling the delivery of agrochemicals/biologics/drugs/fragrances have significant markets in the agriscience/healthcare industries. Here, we report the development of degradable electroactive polymers and their application for the controlled delivery of a clinically relevant drug (the anti-inflammatory dexamethasone phosphate, DMP). Electroactive copolymers composed of blocks of polycaprolactone (PCL) and naturally occurring electroactive pyrrole oligomers (e.g., bilirubin, biliverdin, and hemin) were prepared and solution-processed to produce films (optionally doped with DMP). A combination of in silico/in vitro/in vivo studies demonstrated the cytocompatibility of the polymers. The release of DMP in response to the application of an electrical stimulus was observed to be enhanced by ca. 10-30% relative to the passive release from nonstimulated samples in vitro. Such stimuli-responsive biomaterials have the potential for integration devices capable of delivering a variety of molecules for technical/medical applications.
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Materiales Biocompatibles , Polímeros , Electricidad , PirrolesRESUMEN
Plants produce a variety of high-value chemicals (e.g., secondary metabolites) which have a plethora of biological activities, which may be utilised in many facets of industry (e.g., agrisciences, cosmetics, drugs, neutraceuticals, household products, etc.). Exposure to various different environments, as well as their treatment (e.g., exposure to chemicals), can influence the chemical makeup of these plants and, in turn, which chemicals will be prevalent within them. Essential oils (EOs) usually have complex compositions (>300 organic compounds, e.g., alkaloids, flavonoids, phenolic acids, saponins and terpenes) and are obtained from botanically defined plant raw materials by dry/steam distillation or a suitable mechanical process (without heating). In certain cases, an antioxidant may be added to the EO (EOs are produced by more than 17,500 species of plants, but only ca. 250 EOs are commercially available). The interesting bioactivity of the chemicals produced by plants renders them high in value, motivating investment in their production, extraction and analysis. Traditional methods for effectively extracting plant-derived biomolecules include cold pressing and hydro/steam distillation; newer methods include solvent/Soxhlet extractions and sustainable processes that reduce waste, decrease processing times and deliver competitive yields, examples of which include microwave-assisted extraction (MAE), ultrasound-assisted extraction (UAE), subcritical water extraction (SWE) and supercritical CO2 extraction (scCO2). Once extracted, analytical techniques such as chromatography and mass spectrometry may be used to analyse the contents of the high-value extracts within a given feedstock. The bioactive components, which can be used in a variety of formulations and products (e.g., displaying anti-aging, antibacterial, anticancer, anti-depressive, antifungal, anti-inflammatory, antioxidant, antiparasitic, antiviral and anti-stress properties), are biorenewable high-value chemicals.
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Aceites Volátiles , Saponinas , Antibacterianos/química , Antifúngicos/análisis , Antioxidantes/química , Antiparasitarios , Antivirales/análisis , Dióxido de Carbono/química , Flavonoides , Aceites Volátiles/química , Extractos Vegetales/química , Plantas , Solventes/química , Vapor/análisis , TerpenosRESUMEN
Diabetes is a group of metabolic conditions resulting in high blood sugar levels over prolonged periods that affects hundreds of millions of patients worldwide. Measuring glucose concentration enables patient-specific insulin therapy, and is essential to reduce the severity of the disease, potential complications, and related mortalities. Recent advances and developments in smartphone-based colorimetric glucose detection systems are discussed in this review. The importance of glucose monitoring, data collection, transfer, and analysis, via non-invasive/invasive methods is highlighted. The review also presents various approaches using 3D-printed materials, screen-printed electrodes, polymer templates, designs allowing multiple glucose analysis, bioanalytes and/or nanostructures for glucose detection. The positive effects of advances in improving the performance of smartphone-based platforms are introduced along with future directions and trends in the application of emerging technologies in smartphone-based diagnostics.
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Colorimetría , Diabetes Mellitus , Glucemia , Automonitorización de la Glucosa Sanguínea , Diabetes Mellitus/diagnóstico , Glucosa , Humanos , Teléfono InteligenteRESUMEN
Smart or stimuli-responsive materials are an emerging class of materials used for tissue engineering and drug delivery. A variety of stimuli (including temperature, pH, redox-state, light, and magnet fields) are being investigated for their potential to change a material's properties, interactions, structure, and/or dimensions. The specificity of stimuli response, and ability to respond to endogenous cues inherently present in living systems provide possibilities to develop novel tissue engineering and drug delivery strategies (for example materials composed of stimuli responsive polymers that self-assemble or undergo phase transitions or morphology transformations). Herein, smart materials as controlled drug release vehicles for tissue engineering are described, highlighting their potential for the delivery of precise quantities of drugs at specific locations and times promoting the controlled repair or remodeling of tissues.
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Sistemas de Liberación de Medicamentos/métodos , Polímeros de Estímulo Receptivo/química , Ingeniería de Tejidos/métodos , Materiales Biocompatibles/química , Concentración de Iones de Hidrógeno , Oxidación-Reducción , Transición de Fase , Polímeros/química , Polímeros de Estímulo Receptivo/metabolismo , TemperaturaRESUMEN
Severe burn injuries can lead to delays in healing and devastating scar formation. Attempts have been made to develop a suitable skin substitute for the scarless healing of such skin wounds. Currently, there is no effective strategy for completely scarless healing after the thermal injuries. In our recent work, we fabricated and evaluated a 3D protein-based artificial skin made from decellularized human amniotic membrane (AM) and electrospun nanofibrous silk fibroin (ESF) in vitro. We also characterized both biophysical and cell culture investigation to establish in vitro performance of the developed bilayer scaffolds. In this report, we evaluate the appropriate utility of this fabricated bilayered artificial skin in vivo with particular emphasis on healing and scar formation due to the biochemical and biomechanical complexity of the skin. For this work, AM and AM/ESF membranes alone or seeded with adipose-tissue-derived mesenchymal stem cells (AT-MSCs) are implanted on full-thickness burn wounds in mice. The healing efficacy and scar formation are evaluated at 7, 14, and 28 days post-implantation in vivo. Our data reveal that ESF accelerates the wound-healing process through the early recruitment of inflammatory cells such as macrophages into the defective site as well as the up-regulation of angiogenic factors from the AT-MSCs and the facilitation of the remodeling phase. In vivo application of the prepared AM/ESF membrane seeded with the AT-MSCs reduces significantly the post-burn scars. The in vivo data suggest that the potential applications of the AM/ESF bilayered artificial skin may be considered a clinical translational product with stem cells to guide the scarless healing of severe burn injuries.
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Quemaduras/terapia , Regeneración Tisular Dirigida/métodos , Piel Artificial , Cicatrización de Heridas , Amnios/química , Animales , Fibroínas/química , Masculino , Trasplante de Células Madre Mesenquimatosas/métodos , Células Madre Mesenquimatosas/citología , Ratones , Ratones Endogámicos BALB CRESUMEN
PURPOSE: To develop the first photoactive biomaterial coating capable of controlled drug dosing via inclusion of synthesised drug-3,5-dimethoxybenzoin (DMB) conjugates in a poly(2-methyoxyethyl acrylate) (pMEA) scaffold. METHODS: Flurbiprofen- and naproxen-DMB conjugates were prepared via esterification and characterised via NMR spectroscopy and mass spectrometry following chromatographic purification. Conjugate photolysis was investigated in acetonitrile solution and within the pMEA matrix following exposure to low-power 365 nm irradiation. Photo-liberation of drug from pMEA into phosphate buffered saline was monitored using UV-vis spectroscopy. RESULTS: The synthetic procedures yielded the desired drug conjugates with full supporting characterisation. Drug regeneration through photolysis of the synthesised conjugates was successful in both acetonitrile solution and within the pMEA scaffold upon UV irradiation. Conjugates were retained within the pMEA scaffold with exclusive drug liberation following irradiation and increased drug dose with increasing exposure. Multi-dosing capacity was demonstrated though the ability of successive irradiation periods to generate further bursts of drug. CONCLUSION: This study demonstrates the first application of photochemically controlled drug release from a biomaterial coating and the feasibility of using pMEA as a scaffold for housing the photoactive drug-DMB conjugates.
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Flurbiprofeno/efectos de la radiación , Naproxeno/efectos de la radiación , Ácidos Polimetacrílicos/efectos de la radiación , Antiinflamatorios no Esteroideos/química , Portadores de Fármacos , Liberación de Fármacos , Flurbiprofeno/administración & dosificación , Flurbiprofeno/química , Humanos , Naproxeno/administración & dosificación , Naproxeno/química , Procesos Fotoquímicos , Fotólisis , Ácidos Polimetacrílicos/química , Rayos UltravioletaRESUMEN
We describe, for the first time, stimulus-responsive hydrogel-forming microneedle (MN) arrays that enable delivery of a clinically relevant model drug (ibuprofen) upon application of light. MN arrays were prepared using a polymer prepared from 2-hydroxyethyl methacrylate (HEMA) and ethylene glycol dimethacrylate (EGDMA) by micromolding. The obtained MN arrays showed good mechanical properties. The system was loaded with up to 5% (w/w) ibuprofen included in a light-responsive 3,5-dimethoxybenzoin conjugate. Raman spectroscopy confirmed the presence of the conjugate inside the polymeric MN matrix. In vitro, this system was able to deliver up to three doses of 50 mg of ibuprofen upon application of an optical trigger over a prolonged period of time (up to 160 h). This makes the system appealing as a controlled release device for prolonged periods of time. We believe that this technology has potential for use in "on-demand" delivery of a wide range of drugs in a variety of applications relevant to enhanced patient care.
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Antiinflamatorios no Esteroideos/metabolismo , Sistemas de Liberación de Medicamentos/instrumentación , Hidrogeles/química , Ibuprofeno/metabolismo , Luz , Agujas , Polímeros/química , Administración Cutánea , Antiinflamatorios no Esteroideos/administración & dosificación , Humanos , Ibuprofeno/administración & dosificación , Ensayo de Materiales , Microinyecciones , PielRESUMEN
A huge variety of proteins are able to form fibrillar structures, especially at high protein concentrations. Hence, it is surprising that spider silk proteins can be stored in a soluble form at high concentrations and transformed into extremely stable fibres on demand. Silk proteins are reminiscent of amphiphilic block copolymers containing stretches of polyalanine and glycine-rich polar elements forming a repetitive core flanked by highly conserved non-repetitive amino-terminal and carboxy-terminal domains. The N-terminal domain comprises a secretion signal, but further functions remain unassigned. The C-terminal domain was implicated in the control of solubility and fibre formation initiated by changes in ionic composition and mechanical stimuli known to align the repetitive sequence elements and promote beta-sheet formation. However, despite recent structural data, little is known about this remarkable behaviour in molecular detail. Here we present the solution structure of the C-terminal domain of a spider dragline silk protein and provide evidence that the structural state of this domain is essential for controlled switching between the storage and assembly forms of silk proteins. In addition, the C-terminal domain also has a role in the alignment of secondary structural features formed by the repetitive elements in the backbone of spider silk proteins, which is known to be important for the mechanical properties of the fibre.
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Secuencia Conservada , Seda/química , Seda/metabolismo , Arañas/química , Animales , Rastreo Diferencial de Calorimetría , Dicroismo Circular , Interacciones Hidrofóbicas e Hidrofílicas , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Estructura Terciaria de Proteína , Espectrometría de Fluorescencia , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
Electrical stimulation to manipulate the central nervous system (CNS) has been applied as early as the 1750s to produce visual sensations of light. Deep brain stimulation (DBS), cochlear implants, visual prosthetics, and functional electrical stimulation (FES) are being applied in the clinic to treat a wide array of neurological diseases, disorders, and injuries. This review describes the history of electrical stimulation of the CNS microenvironment; recent advances in electrical stimulation of the CNS, including DBS to treat essential tremor, Parkinson's disease, and depression; FES for the treatment of spinal cord injuries; and alternative electrical devices to restore vision and hearing via neuroprosthetics (retinal and cochlear implants). It also discusses the role of electrical cues during development and following injury and, importantly, manipulation of these endogenous cues to support regeneration of neural tissue.
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Encéfalo/patología , Sistema Nervioso Central/fisiología , Estimulación Encefálica Profunda/métodos , Animales , Implantes Cocleares , Depresión/terapia , Estimulación Eléctrica , Temblor Esencial/terapia , Humanos , Imagen por Resonancia Magnética/métodos , Trastornos del Movimiento/terapia , Enfermedades del Sistema Nervioso/terapia , Enfermedades Neurodegenerativas/terapia , Neuroglía/patología , Neuronas/metabolismo , Enfermedad de Parkinson/patología , Enfermedad de Parkinson/terapia , Sistema Nervioso Periférico/patología , Diseño de Prótesis , Traumatismos de la Médula Espinal/terapia , Células Madre/citologíaRESUMEN
Tissue scaffolds allowing the behavior of the cells that reside within them to be controlled are of particular interest for tissue engineering. Herein, the preparation of conductive fiber-based bone tissue scaffolds (nonwoven mats of electrospun polycaprolactone with an interpenetrating network of polypyrrole and polystyrenesulfonate) is described that enable the electrical stimulation of human mesenchymal stem cells to enhance their differentiation toward osteogenic outcomes.
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Back Cover: Tissue scaffolds allowing the behavior of the cells that reside within them to be controlled are of particular interest for tissue engineering. Herein, the preparation of conductive nanofiber-based bone tissue scaffolds are described, made from nonwoven mats of electrospun polycaprolactone with an interpenetrating network of polypyrrole and polystyrenesulfonate. These scaffolds enable the electrical stimulation of human mesenchymal stem cells to enhance their differentiation toward osteogenic outcomes. Further details can be found in the article by J. G. Hardy,* M. K. Villancio-Wolter, R. C. Sukhavasi, D. J. Mouser, D. Aguilar Jr., S. A. Geissler, D. L. Kaplan,* and C. E. Schmidt* on page 1884.
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Tissues in the body are hierarchically structured composite materials with tissue-specific properties. Urea self-assembles via hydrogen bonding interactions into crystalline supracolloidal assemblies that can be used to impart macroscopic pores to polymer-based tissue scaffolds. In this communication, we explain the solvent interactions governing the solubility of urea and thereby the scope of compatible polymers. We also highlight the role of solvent interactions on the morphology of the resulting supracolloidal crystals. We elucidate the role of polymer-urea interactions on the morphology of the pores in the resulting biomaterials. Finally, we demonstrate that it is possible to use our urea templating methodology to prepare Bombyx mori silk protein-based biomaterials with pores that human dermal fibroblasts respond to by aligning with the long axis of the pores. This methodology has potential for application in a variety of different tissue engineering niches in which cell alignment is observed, including skin, bone, muscle and nerve.
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Materiales Biocompatibles/química , Seda/química , Coloides , Fibroblastos/citología , Fibroblastos/metabolismo , Humanos , Porosidad , Solubilidad , Solventes/química , Andamios del Tejido/química , Urea/químicaRESUMEN
We describe the synthesis of spin-labeled bis-ureas which coassemble with bis-urea gelators and report on self-assembly as detected using electron paramagnetic resonance spectroscopy (EPR). Specifically, EPR detects the gel-sol transition and allows us to quantify how much spin-label is immobilized within the gel fibers and how much is present in mobile solvent pools-as controlled by temperature, gelator structure, and thermal history. EPR is also able to report on the initial self-assembly processes below the gelation threshold which are not macroscopically visible and appears to be more sensitive than NMR to intermediate-sized nongelating oligomeric species. By studying dilute solutions of gelator molecules and using either single or double spin-labels, EPR allows quantification of the initial steps of the hierarchical self-assembly process in terms of cooperativity and association constant. Finally, EPR enables us to estimate the degree of gel-fiber solvation by probing the distances between spin-labels. Comparison of experimental data against the predicted distances assuming the nanofibers are only composed of gelator molecules indicates a significant difference, which can be assigned to the presence of a quantifiable number of explicit solvent molecules. In summary, EPR provides unique data and yields powerful insight into how molecular-scale mobility and solvation impact on assembly of supramolecular gels.
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Metallosupramolecular grid complexes (hereafter referred to as metallogrids) are well-defined oligonuclear metal ion complexes involving essentially planar arrays of the metal ions sited at the points of intersection of square or rectangular metallogrids and possess a variety of interesting optical, electronic, magnetic and supramolecular properties. Herein I aim to give the reader an overview of the synthesis, properties and potential for a variety of high-tech applications of metallogrids.
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Complejos de Coordinación/química , Nanoestructuras/química , Cristalografía por Rayos X , Ligandos , Magnetismo , Modelos Biológicos , Modelos Moleculares , Solventes/químicaRESUMEN
A gel can be defined as a semi-solid structure that has mechanical properties ranging from tough to soft, depending on their constituents [...].
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Injectable in situ-forming scaffolds that induce both angiogenesis and osteogenesis have been proven to be promising for bone healing applications. Here, we report the synthesis of an injectable hydrogel containing cobalt-doped bioactive glass (BG)-loaded microspheres. Silk fibroin (SF)/gelatin microspheres containing BG particles were fabricated through microfluidics. The microspheres were mixed in an injectable alginate solution, which formed an in situ hydrogel by adding CaCl2. The hydrogel was evaluated for its physicochemical properties, in vitro interactions with osteoblast-like and endothelial cells, and bone healing potential in a rat model of calvarial defect. The microspheres were well-dispersed in the hydrogel and formed pores of >100 µm. The hydrogel displayed shear-thinning behavior and modulated the cobalt release so that the optimal cobalt concentration for angiogenic stimulation, cell proliferation, and deposition of mineralized matrix was only achieved by the scaffold that contained BG doped with 5% wt/wt cobalt (A-S-G5Co). In the scaffold containing higher cobalt content, a reduced biomimetic mineralization on the surface was observed. The gene expression study indicated an upregulation of the osteogenic genes of COL1A1, ALPL, OCN, and RUNX2 and angiogenic genes of HIF1A and VEGF at different time points in the cells cultured with the A-S-G5Co. Finally, the in vivo study demonstrated that A-S-G5Co significantly promoted both angiogenesis and osteogenesis and improved bone healing after 12 weeks of follow-up. These results show that incorporation of SF/gelatin microspheres containing cobalt-doped BG in an injectable in situ-forming scaffold can effectively enhance its bone healing potential through promotion of angiogenesis and osteogenesis.
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Microneedle arrays are minimally invasive devices that have been extensively investigated for the transdermal/intradermal delivery of drugs/bioactives. Here, we demonstrate the release of bioactive molecules (estradiol, melatonin and meropenem) from poly(2-hydroxyethyl methacrylate), pHEMA, hydrogel-based microneedle patches in vitro. The pHEMA hydrogel microneedles had mechanical properties that were sufficiently robust to penetrate soft tissues (exemplified here by phantom tissues). The bioactive release from the pHEMA hydrogel-based microneedles was fitted to various models (e.g., zero order, first order, second order). Such pHEMA microneedles have potential application in the transdermal delivery of bioactives (exemplified here by estradiol, melatonin and meropenem) for the treatment of various conditions.
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Light-responsive biomaterials can be used for the delivery of therapeutic drugs and nucleic acids, where the tunable/precise delivery of payload highlights the potential of such biomaterials for treating a variety of conditions. The translucency of eyes and advances of laser technology in ophthalmology make light-responsive delivery of drugs feasible. Importantly, light can be applied in a non-invasive fashion; therefore, light-triggered drug delivery systems have great potential for clinical impact. This review will examine various types of light-responsive polymers and the chemistry that underpins their application as ophthalmic drug delivery systems.
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Materiales Biocompatibles , Sistemas de Liberación de Medicamentos , PolímerosRESUMEN
Fourier domain optical coherence tomography (FD-OCT) is a well-established imaging technique that provides high-resolution internal structure images of an object at a fast speed. Modern FD-OCT systems typically operate at speeds of 40,000-100,000 A-scans/s, but are priced at least tens of thousands of pounds. In this study, we demonstrate a line-field FD-OCT (LF-FD-OCT) system that achieves an OCT imaging speed of 100,000 A-scan/s at a hardware cost of thousands of pounds. We demonstrate the potential of LF-FD-OCT for biomedical and industrial imaging applications such as corneas, 3D printed electronics, and printed circuit boards.
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Additive manufacturing, widely known as 3D printing, has revolutionized the production of biomaterials. While conventional 3D-printed structures are perceived as static, 4D printing introduces the ability to fabricate materials capable of self-transforming their configuration or function over time in response to external stimuli such as temperature, light, or electric field. This transformative technology has garnered significant attention in the field of biomedical engineering due to its potential to address limitations associated with traditional therapies. Here, we delve into an in-depth review of 4D-printing systems, exploring their diverse biomedical applications and meticulously evaluating their advantages and disadvantages. We emphasize the novelty of this review paper by highlighting the latest advancements and emerging trends in 4D-printing technology, particularly in the context of biomedical applications.