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Artificial skin involves multidisciplinary efforts, including materials science, biology, medicine, and tissue engineering. Recent studies have aimed at creating skins that are multifunctional, intelligent, and capable of regenerating tissue. In this work, we present a specialized 3D printing ink composed of polyurethane and bioactive glass (PU-BG) and prepare dual-function skin patch by microfluidic-regulated 3D bioprinting (MRBP) technique. The MRBP endows the skin patch with a highly controlled microstructure and superior strength. Besides, an asymmetric tri-layer is further constructed, which promotes cell attachment and growth through a dual transport mechanism based on hydrogen bonds and gradient structure from hydrophilic to superhydrophilic. More importantly, by combining the features of biomedical skin with electronic skin (e-skin), we achieved a biomedical and electronic dual-function skin patch. In vivo experiments have shown that this skin patch can enhance hemostasis, resist bacterial growth, stimulate the regeneration of blood vessels, and accelerate the healing process. Meanwhile, it also mimics the sensory functions of natural skin to realize signal detection, where the sensitivity reached up to 5.87 kPa-1, as well as cyclic stability (over 500 cycles), a wide detection range of 0-150 kPa, high pressure resolution of 0.1 % under the pressure of 100 kPa. This work offers a versatile and effective method for creating dual-function skin patches and provide new insights into wound healing and tissue repair, which have significant implications for clinical applications.
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Nowadays, immunotherapy is one of the most essential treatments for various diseases and a broad spectrum of disorders are assumed to be treated by altering the function of the immune system. For this reason, immunotherapy has attracted a great deal of attention and numerous studies on different approaches for immunotherapies have been investigated, using multiple biomaterials and carriers, from nanoparticles (NPs) to microneedles (MNs). In this review, the immunotherapy strategies, biomaterials, devices, and diseases supposed to be treated by immunotherapeutic strategies are reviewed. Several transdermal therapeutic methods, including semisolids, skin patches, chemical, and physical skin penetration enhancers, are discussed. MNs are the most frequent devices implemented in transdermal immunotherapy of cancers (e.g., melanoma, squamous cell carcinoma, cervical, and breast cancer), infectious (e.g., COVID-19), allergic and autoimmune disorders (e.g., Duchenne's muscular dystrophy and Pollinosis). The biomaterials used in transdermal immunotherapy vary in shape, size, and sensitivity to external stimuli (e.g., magnetic field, photo, redox, pH, thermal, and even multi-stimuli-responsive) were reported. Correspondingly, vesicle-based NPs, including niosomes, transferosomes, ethosomes, microemulsions, transfersomes, and exosomes, are also discussed. In addition, transdermal immunotherapy using vaccines has been reviewed for Ebola, Neisseria gonorrhoeae, Hepatitis B virus, Influenza virus, respiratory syncytial virus, Hand-foot-and-mouth disease, and Tetanus.
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Neoplasias de la Mama , COVID-19 , Animales , Humanos , Femenino , Sistemas de Liberación de Medicamentos/métodos , Materiales Biocompatibles , COVID-19/terapia , Administración Cutánea , Piel , Liposomas , Inmunoterapia , AgujasRESUMEN
Innovations on materials and technologies have greatly promoted the rapid development of wearable electronics from disease diagnosis to therapeutics. For superficial skin tumors, skin-attachable patches possess the advantages of minimally invasive property, alleviative side effects, and high efficiency. The development of noninvasive techniques and devices is still in urgent demands. Here, a flexible skin patch fabricated through a facile preparation method is reported for noninvasive hybrid thermophysical therapy and adaptative immune function enhancement. The liquid metal enabled skin patch is demonstrated with high conductivity, certain stability, biocompatibility, and an enhanced adhesive merit on skin surfaces for cryoablation therapy and magnetic hyperthermia therapy. The skin patch exhibits remarkably conformable heating and cooling performance toward the treatment of 4T1 breast tumors. The magnetic resonance images also indicate the significant tumor ablation effect. Interestingly, a relatively stable proportion of both CD8+ T and CD4+ T cells in the peripheral blood is identified after tumor therapy in comparison with the decreased trend in the untreated group, representing an efficient antitumor immune response induced by the skin patch. The developed skin patch would provide a promising noninvasive approach for tumor therapies by direct tumor destruction and maintenance of the antitumor immune response.
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Hipertermia Inducida , Neoplasias Cutáneas , Dispositivos Electrónicos Vestibles , Humanos , Parche Transdérmico , InmunidadRESUMEN
The skin is a complex layer system and the most important barrier between the environment and the organism. In this review, we describe some widespread skin problems, with a focus on eczema, which are affecting more and more people all over the world. Most of treatment methods for atopic dermatitis (AD) are focused on increasing skin moisture and protecting from bacterial infection and external irritation. Topical and transdermal treatments have specific requirements for drug delivery. Breathability, flexibility, good mechanical properties, biocompatibility, and efficacy are important for the patches used for skin. Up to today, electrospun fibers are mostly used for wound dressing. Their properties, however, meet the requirements for skin patches for the treatment of AD. Active agents can be incorporated into fibers by blending, coaxial or side-by-side electrospinning, and also by physical absorption post-processing. Drug release from the electrospun membranes is affected by drug and polymer properties and the technique used to combine them into the patch. We describe in detail the in vitro release mechanisms, parameters affecting the drug transport, and their kinetics, including theoretical approaches. In addition, we present the current research on skin patch design. This review summarizes the current extensive know-how on electrospun fibers as skin drug delivery systems, while underlining the advantages in their prospective use as patches for atopic dermatitis. This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement Therapeutic Approaches and Drug Discovery > Emerging Technologies.
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Dermatitis Atópica , Humanos , Dermatitis Atópica/tratamiento farmacológico , Piel , Sistemas de Liberación de Medicamentos , Cicatrización de Heridas , VendajesRESUMEN
In the present study, the preparation of controlled-released leflunomide (LFD)-loaded skin patches was evaluated, utilizing the combination of chitosan (CS) nanoparticles (NPs) incorporated into suitable poly(l-lactic acid) (PLLA) or poly(lactic-co-glycolic acid) (PLGA) polyester matrices. Initially, LFD-loaded CS NPs of ~600 nm and a smooth surface were prepared, while strong inter-molecular interactions between the drug and the CS were unraveled. In the following step, the prepared LFD-loaded CS NPs were incorporated into PLLA or PLGA, and thin-film patches were prepared via spin-coating. Analysis of the prepared films showed that the incorporation of the drug-loaded CS NPs resulted in a significant increase in the drug's release rate and extent as compared to neat LFD-loaded polyester patches (i.e., prepared without the use of CS NPs). In-depth analysis of the prepared formulations showed that the amorphization of the drug within the matrix and the increased wetting properties of the prepared CS NPs were responsible for the improved thin-film patch characteristics.
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Atopic dermatitis (eczema), one of the most common disease and also most difficult to treat, is seeking for novel development not only in medicine but also in bioengineering. Moisturization is the key in eczema treatment as dry skin triggers inflammation that damages the skin barrier. Thus, here we combine electrospun hydrophobic polystyrene (PS) and hydrophilic nylon 6 (PA6) with oils to create patches helping to moisturize atopic skin. The fibrous membranes manufactured using electrospinning: PS, PA6, composite PS - PA6 and sandwich system combining them were characterized by water vapor transmission rates (WVTR) and fluid uptake ability (FUA). To create the most effective moisturizing patches we use borage, black cumin seed and evening primrose oil and tested their spreading. We show a great potential of our designed patches, the oil release tests on a skin and their moisturizing effect were verified. Our results distinctly reveal that both fiber sizes and hydrophilicity/hydrophobicity of polymer influence oil spreading, release from membranes and WVTR measurements. Importantly, the direct skin test indicates the evident increase of hydration for both dry and normal skin after using the patches. The electrospun patches based on the hydrophobic and hydrophilic polymers have outstanding properties to be used as oil carriers for atopic dermatitis treatment.
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Dermatitis Atópica , Eccema , Dermatitis Atópica/tratamiento farmacológico , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , PielRESUMEN
Increasing evidence suggests that in hosts infected with parasites of the Leishmania donovani complex, transmission of infection to the sand fly vector is linked to parasite repositories in the host skin. However, a detailed understanding of the dispersal (the mechanism of spread) and dispersion (the observed state of spread) of these obligatory-intracellular parasites and their host phagocytes in the skin is lacking. Using endogenously fluorescent parasites as a proxy, we apply image analysis combined with spatial point pattern models borrowed from ecology to characterize dispersion of parasitized myeloid cells (including ManR+ and CD11c+ cells) and predict dispersal mechanisms in a previously described immunodeficient model of L. donovani infection. Our results suggest that after initial seeding of infection in the skin, heavily parasite-infected myeloid cells are found in patches that resemble innate granulomas. Spread of parasites from these initial patches subsequently occurs through infection of recruited myeloid cells, ultimately leading to self-propagating networks of patch clusters. This combination of imaging and ecological pattern analysis to identify mechanisms driving the skin parasite landscape offers new perspectives on myeloid cell behavior following parasitism by L. donovani and may also be applicable to elucidating the behavior of other intracellular tissue-resident pathogens and their host cells.
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Procesamiento de Imagen Asistido por Computador , Leishmania donovani/patogenicidad , Leishmaniasis Visceral/parasitología , Microscopía Confocal , Microscopía Fluorescente , Células Mieloides/parasitología , Piel/parasitología , Análisis Espacial , Animales , Antígenos CD11/metabolismo , Análisis por Conglomerados , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Modelos Animales de Enfermedad , Interacciones Huésped-Parásitos , Insectos Vectores/parasitología , Leishmania donovani/inmunología , Leishmaniasis Visceral/inmunología , Leishmaniasis Visceral/metabolismo , Leishmaniasis Visceral/transmisión , Receptor de Manosa/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Modelos Teóricos , Células Mieloides/inmunología , Células Mieloides/metabolismo , Phlebotomus/parasitología , Piel/inmunología , Piel/metabolismoRESUMEN
Patients with psoriasis are dissatisfied with the standard pharmacological treatments, whether systemic or topical, with many of them showing interest in complementary and alternative medicine. Curcumin (Cur), a natural polyphenol derived from turmeric, has recently gained attention for skin-related diseases because of its proven anti-inflammatory action. However, topical treatment with Cur would be inadequate because of its hydrophobicity, instability, and low bioavailability. In addition, hyperkeratosis and lack of moisture in psoriatic skin result in low penetration that would prevent actives from permeating the stratum corneum. In this work, a polymer-based formulation of Cur for the topical treatment of psoriasis is reported. To improve the physicochemical stability of Cur, it was first encapsulated in chitosan nanoparticles. The Cur-loaded nanoparticles were incorporated in a hydrophilic, biocompatible collagen-based patch. The nanoparticle-containing porous collagen patches were then chemically cross-linked. Morphology, chemical interactions, swelling ratio, enzymatic hydrolysis, and Cur release from the patches were evaluated. All patches showed excellent swelling ratio, up to ~1500%, and after cross-linking, the pore size decreased, and their hydrolysis rates decelerated. The in vitro release of Cur was sustained with an initial burst release, reaching 55% after 24 h. Cur within the scaffolds imparted a proliferation inhibitory effect on psoriatic human keratinocytes in vitro.
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AIMS: To evaluate the effectiveness and safety of Xin Huang Pian skin patches for patients with acute gouty arthritis. BACKGROUND: In China, patients with acute gouty arthritis benefit from skin patcheses with herbal medicines. But the clinical effects of skin patches with Xin Huang Pian are rarely reported. DESIGN: A Randomized, Double-Blind, Active-Controlled Trial. METHODS: The trial was performed from January 2015-December 2018 at the First Affiliated Hospital of Sun Yat-sen University in China. It was conducted with one intervention group (skin patches of Xin Huang Pian, N = 30) and one active control group (skin patches of Diclofenac Diethylamine Emulgel, N = 31). Participants and study investigators were both blinded to the treatment assignments. The primary outcomes were the improvement of joints' symptoms. The secondary outcomes were changes in white blood cells, erythrocyte sedimentation rate and C-reactive protein. RESULTS: Skin patches of Xin Huang Pian showed quick effect on decreasing joint pain at 3rd day of treatment. Wherever only at 7th day, Diclofenac Diethylamine Emulgel markedly lowered joint pain. Xin Huang Pian also showed superior effect than Diclofenac Diethylamine Emulgel on improving joint swelling and range of motion and decreasing the levels of C-reactive protein and erythrocyte sedimentation rate. No adverse reactions were observed in skin patches of Xin Huang Pian treatment. CONCLUSION: Skin patches of Xin Huang Pian appeared to be safe and efficacious for relieving joint symptoms in patients with acute gouty arthritis. The mechanism might be associated with the decreased levels of C-reactive protein and erythrocyte sedimentation rate. IMPACT: Skin-patcheses with Xin Huang Pian are more effective than Diclofenac Diethylamine Emulgel on improving joint pain, swelling and range of motion. Xin Huang Pian treatment showed superior effects compared with Diclofenac Diethylamine Emulgel on decreasing levels of C-reactive protein and erythrocyte sedimentation rate. Patients with acute gouty arthritis may benefit from skin patches of Xin Huang Pian for effective relief from joint pain and swelling. Chinese Clinical Trial Registration: ChiCTR-TRC-1300 4122.
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Analgésicos/uso terapéutico , Antiinflamatorios/uso terapéutico , Artritis Gotosa/tratamiento farmacológico , Diclofenaco/uso terapéutico , Dietilaminas/uso terapéutico , Medicamentos Herbarios Chinos/uso terapéutico , Supresores de la Gota/uso terapéutico , Administración Cutánea , Analgésicos/administración & dosificación , Antiinflamatorios/administración & dosificación , China , Diclofenaco/administración & dosificación , Método Doble Ciego , Medicamentos Herbarios Chinos/administración & dosificación , Femenino , Supresores de la Gota/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Fitoterapia , Distribución AleatoriaRESUMEN
Recent advances in biosensors and point-of-care (PoC) devices are poised to change and expand the delivery of diagnostics from conventional lateral-flow assays and test strips that dominate the market currently, to newly emerging wearable and implantable devices that can provide continuous monitoring. Soft and flexible materials are playing a key role in propelling these trends towards real-time and remote health monitoring. Affinity biosensors have the capability to provide for diagnosis and monitoring of cancerous, cardiovascular, infectious and genetic diseases by the detection of biomarkers using affinity interactions. This review tracks the evolution of affinity sensors from conventional lateral-flow test strips to wearable/implantable devices enabled by soft and flexible materials. Initially, we highlight conventional affinity sensors exploiting membrane and paper materials which have been so successfully applied in point-of-care tests, such as lateral-flow immunoassay strips and emerging microfluidic paper-based devices. We then turn our attention to the multifarious polymer designs that provide both the base materials for sensor designs, such as PDMS, and more advanced functionalised materials that are capable of both recognition and transduction, such as conducting and molecularly imprinted polymers. The subsequent content discusses wearable soft and flexible material-based affinity sensors, classified as flexible and skin-mountable, textile materials-based and contact lens-based affinity sensors. In the final sections, we explore the possibilities for implantable/injectable soft and flexible material-based affinity sensors, including hydrogels, microencapsulated sensors and optical fibers. This area is truly a work in progress and we trust that this review will help pull together the many technological streams that are contributing to the field.
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Técnicas Biosensibles , Dispositivos Electrónicos Vestibles , Hidrogeles , Dispositivos Laboratorio en un Chip , PolímerosRESUMEN
Atopic dermatitis (AD) is a chronic, inflammatory skin condition, caused by wide genetic, environmental, or immunologic factors. AD is very common in children but can occur at any age. The lack of long-term treatments forces the development of new strategies for skin regeneration. Polycaprolactone (PCL) is a well-developed, tissue-compatible biomaterial showing also good mechanical properties. In our study, we designed the electrospun PCL patches with controlled architecture and topography for long-term release in time. Hemp oil shows anti-inflammatory and antibacterial properties, increasing also the skin moisture without clogging the pores. It can be used as an alternative cure for patients that do not respond to traditional treatments. In the study, we tested the mechanical properties of PCL fibers, and the hemp oil spreading together with the release in time measured on skin model and human skin. The PCL membranes are suitable material as patches or bandages, characterized by good mechanical properties and high permeability. Importantly, PCL patches showed release of hemp oil up to 55% within 6 h, increasing also the skin moisture up to 25%. Our results confirmed that electrospun PCL patches are great material as oil carriers indicating a high potential to be used as skin patches for AD skin treatment.
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The attachment phenomena of various hierarchical architectures found in nature have extensively drawn attention for developing highly biocompatible adhesive on skin or wet inner organs without any chemical glue. Structural adhesive systems have become important to address the issues of human-machine interactions by smart outer/inner organ-attachable devices for diagnosis and therapy. Here, advances in designs of biologically inspired adhesive architectures are reviewed in terms of distinct structural properties, attachment mechanisms to biosurfaces by physical interactions, and noteworthy fabrication methods. Recent demonstrations of bioinspired adhesive architectures as adhesive layers for medical applications from skin patches to multifunctional bioelectronics are presented. To conclude, current challenges and prospects on potential applications are also briefly discussed.
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Adhesivos/química , Materiales Biomiméticos/química , Parche Transdérmico , Animales , Técnicas Biosensibles/instrumentación , Técnicas Biosensibles/métodos , Electrónica , Humanos , Polímeros/químicaRESUMEN
A skin adhesive patch is the most fundamental and widely used medical device for diverse health-care purposes. Conventional skin adhesive patches have been mainly utilized for routine medical purposes such as wound management, fixation of medical devices, and simple drug release. In contrast to traditional skin adhesive patches, recently developed patches incorporate multiple key functions of bulky medical devices into a thin, flexible patch based on emerging nanomaterials and flexible electronic technologies. Consequently, the meaning of the term "skin adhesive patch" becomes broader and smarter compared to the traditional term. This review summarizes recent efforts undertaken in the development of multifunctional advanced skin adhesive patches, and briefly describes future directions and challenges toward the next generation of smart skin adhesive patches for ubiquitous personalized health care.
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Sistemas de Liberación de Medicamentos/métodos , Parche Transdérmico , Administración Cutánea , HumanosRESUMEN
This article describes the preparation, quality control, and biological evaluation of (90)Y-skin patches based on Nafion(®) membrane as a viable treatment modality for superficial skin tumors such as melanoma. To arrive at the conditions for optimum uptake of (90)Y on the membrane, influence of various experimental parameters, such as pH of the feed solution, inactive yttrium carrier concentration, reaction volume, contact time, and temperature, was systematically investigated. Under the optimized conditions, >95% of the (90)Y activity (37-185 MBq) could be incorporated in the Nafion membranes to prepare (90)Y-skin patches. Quality control tests were carried out to ensure nonleachability, uniform distribution of activity, and stability of the (90)Y-patches. Mice bearing transplanted melanoma tumors that were treated with two doses of 74 MBq (90)Y-Nafion membrane sources showed complete tumor regression. Histopathological examination of the treated area showed absence of tumor. The results of the study indicate the potential of (90)Y-Nafion membrane sources for treatment of superficial skin tumors.