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Background: Terbinafine hydrochloride (TEB) is a broad-spectrum antifungal medication commonly used to treat fungal infections of the skin. This study designed a hydrogel patch assisted by an iontophoresis system to enhance the transdermal permeability of TEB, enabling deeper penetration into the skin layers. Methods: The influences of current intensity, pH levels, and drug concentration on the TEB hydrogel patch's permeability were explored using an adaptive ion electroosmosis system. The pharmacokinetic profile, facilitated by iontophoresis for transdermal permeation, was analyzed through the application of microdialysis technology. Scanning electron microscopy and transmission electron microscopy were employed to assess the impact of ion electroosmotic systems on skin integrity. Results: The cumulative drug accumulation within 8 h of the TEB hydrogel patches, assisted by iontophoresis, was 2.9 and 7.9 times higher than without iontophoresis assistance and TEB cream in the control group, respectively. TEB hydrogel patches assisted by iontophoresis can significantly increase the permeability of TEB, and the AUC(0-8 h) was 3.4 and 5.4 times higher, while the Cmax was 4.2 and 7.3 times higher than the TEB hydrogel patches without iontophoresis, respectively. This system has no significant impact on deep-layer cells. Conclusions: This system may offer a safe and effective clinical strategy for the local treatment of deep antifungal infections.
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Postoperative adhesion is a common complication after abdominal surgery, but current clinical products have unsatisfactory therapeutic effects. Here, we present a hydrogel patch formed in a single step through dialysis. The exchange of DMSO into water facilitates hydrophobic aggregate in situ formation and the formation of hydrogen bonds within the hydrogel. Thanks to the optimized component ratio and precise structural design. The hydrogel patch has soft-tissue-like mechanical characteristics, including high strength, high toughness, low modulus similar to the abdominal wall, good fatigue resistance, and fast self-recovery properties. The nonswellable hydrogel patch retains over 80% of its original mechanical properties after 7 days of immersion in physiological saline, with a maximum swelling ratio of 5.6%. Moreover, the hydrophobic biomultifunctionality of benzyl isothiocyanate can self-assemble onto the hydrogel patch during the sol-gel transition process, enabling it to remodel the inflammatory microenvironment through synergistic antibacterial, antioxidant, and anti-inflammatory effects. The hydrogel patch prevents postsurgical adhesion in a rat sidewall defect-cecum abrasion model and outperforms the leading commercial Interceed. It holds promising potential for clinical translation, considering that FDA-approved raw materials (PVA and gelatin) form the backbone of this effective hydrogel patch.
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Hidrogéis , Hidrogéis/química , Hidrogéis/farmacologia , Animais , Ratos , Aderências Teciduais/prevenção & controle , Ratos Sprague-Dawley , Antibacterianos/farmacologia , Antibacterianos/química , Masculino , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologiaRESUMO
Bacterial infections are among the most critical global health challenges that seriously threaten the security of human. To address this issue, a biocompatible engineered living hydrogel patch was developed by co-embedding engineered photothermal bacteria (EM), photosensitizer (porphyrin) and reactive oxygen species amplifier (laccase) in a protein hydrogel. Remarkably, the genetice engineered bacteria can express melanin granules in vivo and this allows them to exhibit photothermal response upon being exposed to NIR-II laser (1064 nm) irradiation. Besides, electrostatically adhered tetramethylpyridinium porphyrin (TMPyP) on the bacterial surface and encapsulated laccase (Lac) in protein gel can generate highly toxic singlet oxygen (1O2) and hydroxyl radical (·OH) in the presence of visible light and lignin, respectively. Interestingly, the engineered bacteria hydrogel patch (EMTL@Gel) was successfully applied in synergistic photothermal, photodynamic and chemodynamic therapy, in which it was able to efficiently treat bacterial infection in mouse wounds and enhance wound healing. This work demonstrates the concept of "fighting bacteria with bacteria" combining bacterial engineering and material engineering into an engineered living hydrogel path that can synergistically boost the therapeutic outcome. STATEMENT OF SIGNIFICANCE: Genetically engineered bacteria produce melanin granules in vivo, exhibiting remarkable photothermal properties. These bacteria, along with a photosensitizer (TMPyP) and a reactive oxygen species amplifier (laccase), are incorporated into a biocompatible protein hydrogel patch. Under visible light, the patch generates toxic singlet oxygen (1O2) and hydroxyl radical (·OH), demonstrates outstanding synergistic effects in photothermal, photodynamic, and chemodynamic therapy, effectively treating bacterial infections and promoting wound healing in mice.
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Hidrogéis , Cicatrização , Cicatrização/efeitos dos fármacos , Animais , Hidrogéis/química , Hidrogéis/farmacologia , Camundongos , Infecções Bacterianas/tratamento farmacológico , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Lacase/química , Porfirinas/química , Porfirinas/farmacologia , Escherichia coli/efeitos dos fármacosRESUMO
The current wound healing process faces numerous challenges such as bacterial infection, inflammation and oxidative stress. However, wound dressings used to promote wound healing, are not well suited to meet the clinical needs. Hyaluronic acid (HA) not only has excellent water absorption and good biocompatibility but facilitates cell function and tissue regeneration. Dopamine, on the other hand, increases the overall viscosity of the hydrogel and possesses antioxidant property. Furthermore, chitosan exhibits outstanding performance in antimicrobial, anti-inflammatory and antioxidant activities. Basic fibroblast growth factor (bFGF) is conducive to cell proliferation and migration, vascular regeneration and wound healing. Hence, we designed an all-in-one hydrogel patch containing dopamine and chitosan framed by hyaluronic acid (HDC) with sprayed gelatin methacryloyl (GelMA) microspheres loaded with bFGF (HDC-bFGF). The hydrogel patch exhibits excellent adhesive, anti-inflammatory, antioxidant and antibacterial properties. In vitro experiments, the HDC-bFGF hydrogel patch not only showed significant inhibitory effect on RAW cell inflammation and Staphylococcus aureus (S. aureus) growth but also effectively scavenged free radicals, in addition to promoting the migration of 3 T3 cells. In the mice acute infected wound model, the HDC-bFGF hydrogel patch adhered to the wound surface greatly accelerated the healing process via its anti-inflammatory and antioxidant activities, bacterial inhibition and pro-vascularization effects. Therefore, the multifunctional HDC-bFGF hydrogel patch holds great promise for clinical application.
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Antibacterianos , Anti-Inflamatórios , Antioxidantes , Quitosana , Fator 2 de Crescimento de Fibroblastos , Gelatina , Hidrogéis , Metacrilatos , Microesferas , Staphylococcus aureus , Cicatrização , Animais , Cicatrização/efeitos dos fármacos , Camundongos , Fator 2 de Crescimento de Fibroblastos/administração & dosagem , Fator 2 de Crescimento de Fibroblastos/química , Fator 2 de Crescimento de Fibroblastos/farmacologia , Gelatina/química , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Antibacterianos/química , Hidrogéis/química , Hidrogéis/administração & dosagem , Quitosana/química , Quitosana/administração & dosagem , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Antioxidantes/química , Metacrilatos/química , Metacrilatos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Masculino , Dopamina/administração & dosagem , Dopamina/química , Dopamina/farmacologia , Ácido Hialurônico/química , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/farmacologia , Células RAW 264.7 , Movimento Celular/efeitos dos fármacos , Infecção dos Ferimentos/tratamento farmacológicoRESUMO
Nonhealing diabetic wounds are predominantly attributed to the inhibition of angiogenesis, re-epithelialization, and extracellular matrix (ECM) synthesis caused by hypoxia. Although oxygen therapy has demonstrated efficacy in promoting healing, its therapeutic impact remains suboptimal due to unsustainable oxygenation. Here, this work proposes an oxygen-releasing hydrogel patch embedded with polyethylene glycol-modified calcium peroxide microparticles, which sustainably releases oxygen for 7 days without requiring any supplementary conditions. The released oxygen effectively promotes cell migration and angiogenesis under hypoxic conditions as validated in vitro. The in vivo tests in diabetic mice models show that the sustainably released oxygen significantly facilitates the synthesis of ECM, induces angiogenesis, and decreases the expression of inflammatory cytokines, achieving a diabetic wound healing rate of 84.2% on day 7, outperforming the existing oxygen-releasing approaches. Moreover, the proposed hydrogel patch is designed with porous, soft, antibacterial, biodegradable, and storage stability for 15 days. The proposed hydrogel patch is expected to be promising in clinics treating diabetic wounds.
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Diabetes Mellitus Experimental , Hidrogéis , Oxigênio , Peróxidos , Cicatrização , Cicatrização/efeitos dos fármacos , Animais , Hidrogéis/química , Hidrogéis/farmacologia , Camundongos , Oxigênio/química , Peróxidos/química , Peróxidos/farmacologia , Humanos , Polietilenoglicóis/química , Neovascularização Fisiológica/efeitos dos fármacos , Masculino , Células Endoteliais da Veia Umbilical Humana , Movimento Celular/efeitos dos fármacosRESUMO
Myocardial infarction (MI) results in an impaired heart function. Conductive hydrogel patch-based therapy has been considered as a promising strategy for cardiac repair after MI. In our study, we fabricated a three-dimensional (3D) printed conductive hydrogel patch made of fibrinogen scaffolds and mesenchymal stem cells (MSCs) combined with graphene oxide (GO) flakes (MSC@GO), capitalizing on GO's excellent mechanical property and electrical conductivity. The MSC@GO hydrogel patch can be attached to the epicardium via adhesion to provide strong electrical integration with infarcted hearts, as well as mechanical and regeneration support for the infarcted area, thereby up-regulating the expression of connexin 43 (Cx43) and resulting in effective MI repair in vivo. In addition, MI also triggers apoptosis and damage of cardiomyocytes (CMs), hindering the normal repair of the infarcted heart. GO flakes exhibit a protective effect against the apoptosis of implanted MSCs. In the mouse model of MI, MSC@GO hydrogel patch implantation supported cardiac repair by reducing cell apoptosis, promoting gap connexin protein Cx43 expression, and then boosting cardiac function. Together, this study demonstrated that the conductive hydrogel patch has versatile conductivity and mechanical support function and could therefore be a promising candidate for heart repair.
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Grafite , Hidrogéis , Infarto do Miocárdio , Ratos , Camundongos , Animais , Hidrogéis/farmacologia , Conexina 43 , Ratos Sprague-Dawley , Infarto do Miocárdio/cirurgia , Condutividade Elétrica , Impressão TridimensionalRESUMO
Purpose: Chronic inflammatory pain is usually treated with oral non-steroidal anti-inflammatory drugs (NSAIDs). However, oral NSAIDs can cause some adverse events, and local preparation is an important alternative drug. Currently, small sample clinical studies show that loxoprofen sodium hydrogel patch (LX-P) has good analgesic and anti-inflammatory effects; however, there is a lack of real-world clinical research data. Patients and Methods: This study included 60 patients with chronic inflammatory pain. They were treated with LX-P without affecting their real-world treatment for two weeks. Results: After 2 weeks of continuous medication, 93.33% of the patients stated that the treatment was effective. Only 3.33% of the patients had a relapse after 4 weeks. Moreover, the swelling range and degree of swelling decreased markedly and the dysfunction of the pain site was markedly alleviated. The total satisfaction of patients after treatment reached 90.00%. Conclusion: In this real-world observational study, LX-P showed good efficacy and safety in patients with chronic inflammatory pain.
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The prolonged use of Personal Protective Equipment (PPE) can lead to skin problems due to persistent pressure, friction, and tension. This issue has prompted the exploration of solutions to protect the skin while maintaining the effectiveness of the PPE. This study aimed to evaluate the in vivo effectiveness of a gelatin/tannic acid-based hydrogel patch positioned beneath a mask to alleviate skin damage resulting from mask-wearing. To understand the pressure exerted by PPE, in vitro tests were conducted to measure the tensile strength of three types of facial masks. The FFP2 masks exhibited the highest tensile strength and were selected for subsequent in vivo biometric investigations. Biometric parameters were evaluated using the Flir E50bx® thermographic camera, Corneometer®, MoistureMap®, Sebumeter®, Tewameter®, and VISIA® systems. The results showed that when the hydrogel patch was used under the mask, there were no significant differences in facial skin temperature, sebum levels, or TEWL values (p > 0.05). However, a statistically significant increase in skin hydration and a decrease in frontal redness (p < 0.05) were observed. Consumer acceptance was assessed through sensory analysis questionnaires. In summary, the observed attenuation of physiological changes in the facial area and the positive consumer feedback suggest that this polymeric film-forming system is a simple yet effective solution to prevent PPE use-related skin issues.
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Gelatina , Hidrogéis , Humanos , Equipamento de Proteção Individual , Eritema , Pessoal de Saúde , MáscarasRESUMO
Background and purpose: Crinum asiaticum L. has long been used in Thai traditional medicine to treat osteoarthritis and inflammation by placing it on painful areas without further formulation design which is suboptimal for therapeutic use. Thus, this research aims to formulate a topical hydrogel patch containing C. asiaticum L. extracts (CAE) for anti-inflammatory effects. Experimental approach: The hydrogel patches are made from carrageenan, locust bean gum, with glycerin as a plasticizer and contain CAE formulated by using response surface methodology based on Box-Behnken design for design, determination of the effect of independent factors on the tensile strength, and optimization of the hydrogel patch formulation. In vitro release and skin permeation studies using a modified Franz diffusion cell and anti-inflammatory activity were evaluated. Findings/Results: The optimized CAE hydrogel patch showed a good correlation between predicted and observed tensile strength values and exerted its maximum cumulative lycorine release and permeation at 69.38 ± 2.78% and 48.51 ± 0.45%, respectively which were fit to Higuchi's kinetic model. The release rates were found to decrease with an increase in the polymer proportion of carrageenan and locust bean gum. In addition, the patch exerted potent in vitro anti-inflammatory activity with an IC50 value of 21.36 ± 0.78 µg/mL. Conclusion and implication: The optimized CAE hydrogel patch application was successfully formulated with excellent mechanical properties, cumulative release, permeation, and anti-inflammatory effects. Thus, it has the potential to be further developed as a herbal application to relieve pain and inflammation. The in vivo anti-inflammatory effect of this delivery system should be further investigated.
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A hydrogel topical patch of neomycin was developed by using sodium alginate (SA) and hydroxyethylcellulose (HEC) as polymers. Free radical polymerization in an aqueous medium was initiated by using acrylic acid (AA) and N,N'-methylenebisacrylamide (MBA). Prepared hydrogels were characterized for pH sensitivity and sol-gel analysis. In addition, the effect of reactant contents on the developed formulation was evaluated by swelling behavior. SEM assay showed the rough structure of the hydrogel-based polymeric matrix, which directly enhances the ability to uptake fluid. FTIR spectra revealed the formation of a new polymeric network between reactant contents. TGA and DSC verified that fabricated polymeric patches were more thermodynamically stable than pure components. Gel fractions increased with increases in polymer, monomer, and cross-linker contents. The swelling study showed the pH-dependent swelling behavior of patches at pH 5.5, 6.5, and 7.4. The release pattern of the drug followed zero-order kinetics, with diffusion-controlled drug release patterns according to the Korsmeyer-Peppas (KP) model. Ex vivo studies across excised rabbit skin verified the drug retention in the skin layers. The hydrogel patch effectively healed the wounds produced on the rabbit skin, whereas the formulation showed no sign of irritation on intact skin. Therefore, neomycin hydrogel patches can be a potential candidate for controlled delivery for efficient wound healing.
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In this study, we prepared visible light-curable methacrylated glycol chitosan (MGC) hydrogel patches for the prenatal treatment of fetal myelomeningocele (MMC) and investigated their feasibility using a retinoic acid-induced fetal MMC rat model. 4, 5, and 6 w/v% of MGC were selected as candidate precursor solutions, and photo-cured for 20 s, because the resulting hydrogels were found to possess concentration dependent tunable mechanical properties and structural morphologies. Moreover, these materials exhibited no foreign body reactions with good adhesive properties in animal studies. The inflammation scoring assessment in vivo exhibited the absence of foreign body reactions in MGC hydrogel treated lesion. The complete epithelial coverage of MMC was made with using 6 w/v% MGC hydrogel followed by well-organized granulation along with noticeable decrease of abortion rate and wound size that highlight the therapeutic potential for the prenatal treatment of fetal MMC.
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Quitosana , Meningomielocele , Gravidez , Feminino , Ratos , Animais , Meningomielocele/induzido quimicamente , Hidrogéis/química , Quitosana/química , LuzRESUMO
Dragon's Blood is a member of the Chinese medicinal herb, having anti-oxygen and anti-inflammatory activity for the photoprotective effect. However, the poor water solubility of raw Dragon's Blood powder has limited its intradermal delivery process. In this study, we evaluated nanosuspensions to enhance intradermal delivery of Dragon's Blood exerting a photoprotective effect. The prepared nanosuspension was added to a composite hydrogel patch matrix for better skin application. In the present research, we used biocompatible materials hyaluronic acid and amino acid surfactants as nanosuspension stabilizers and agar/gelatin/sodium polyacrylate as hydrogel patch matrix. The prepared Dragon's Blood nanosuspension had a particle size of 447.0 ± 48.6 nm. The micro-structures morphology and viscoelasticity characteristics by SEM and rheological testing confirmed a sufficient crosslinked hydrogel network. The skin retention amount of Dragon's Blood nanosuspension was 1.48 times of raw Dragon's Blood powder water suspension, and the skin penetration amount of Dragon's Blood nanosuspension was only about 1/3 of Dragon's Blood DMSO solution. In the UVB-irradiated HaCaT cell phototoxicity model, Dragon's Blood nanosuspension also significantly increased cell viability by about 1 time of the model group and decreased the production of reactive oxygen species about 1/2 times of model group. In vivo safety and efficiency evaluation experiment illustrated that DB-NS hydrogel patch processes have favorable safety and photoprotective effect with no skin irritancy and phototoxicity. Furthermore, DB-NS and DB-NS hydrogel patches could protect skin from UVA and UVB irritating skin reactions. Overall, our study of the combined use of biocompatible and biodegradable materials as excipients of nanosuspension and hydrogel patch could be used as an effective additive of Intradermal delivery and skin photoprotection.
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Hidrogéis , Resinas Vegetais , Humanos , Pós , Resinas Vegetais/química , Extratos Vegetais/químicaRESUMO
Oral wounds under diabetic conditions display a significant delay during the healing process, mainly due to oxidative stress-induced inflammatory status and abnormal immune responses. Besides, the wet and complicated dynamic environment of the oral cavity impedes stable treatment of oral wounds. To overcome these, a biomimetic hydrogel adhesive was innovatively developed based on a mussel-inspired multifunctional structure. The adhesive displays efficient adhesion and mechanical harmony on the oral mucosa through enhanced bonding in an acidic proinflammatory environment. The bioadhesive hydrogel exhibits excellent antioxidative properties by mimicking antioxidative enzymatic activities to reverse reactive oxygen species (ROS)-mediated immune disorders. Experiments on oral wounds of diabetic rats showed that this hydrogel adhesive could effectively protect against mucosal wounds and obviously shorten the inflammatory phase, thus promoting the wound-healing process. Therefore, this study offers a promising therapeutic choice with the potential to advance the clinical treatment of diabetic oral wounds.
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Diabetes Mellitus Experimental , Diabetes Mellitus , Animais , Ratos , Hidrogéis/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Aceleração , Antioxidantes , CicatrizaçãoRESUMO
Hydrogel patch-based stem cell transplantation and microenvironment-regulating drug delivery strategy is promising for the treatment of myocardial infarction (MI). However, the low retention of cells and drugs limits their therapeutic efficacies. Here, we propose a prefixed sponge carpet strategy, that is, aldehyde-dextran sponge (ODS) loading anti-oxidative/autophagy-regulating molecular capsules of 2-hydroxy-ß-cyclodextrin@resveratrol (HP-ß-CD@Res) is first bonded to the rat's heart via capillary removal of interfacial water from the tissue surface, and the subsequent Schiff base reaction between the aldehyde groups on ODS and amino groups on myocardium tissue. Then, an aqueous biocompatible hydrazided hyaluronic acid (HHA) solution encapsulating mesenchymal stem cells (MSCs) is impregnated into the anchored carpet to form HHA@ODS@HP-ß-CD@Res hydrogel in situ via click reaction, thus prolonging the in vivo retention time of therapeutic drug and cells. Importantly, the HHA added to outer surface consumes the remaining aldehydes to contribute to nonsticky top surface, avoiding adhesion to other tissues. The embedded HP-ß-CD@Res molecular capsules with antioxidant and autophagy regulation bioactivities can considerably improve cardiac microenvironment, reduce cardiomyocyte apoptosis, and enhance the survival of transplanted MSCs, thereby promoting cardiac repair by facilitating angiogenesis and reducing cardiac fibrosis.
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Background and purpose: Garcinia mangostana, simply known as mangosteen, has long been used by Thai traditional medicine because of its reported antibacterial and anti-inflammatory activities for the treatment of skin infections. In this study, mangosteen pericarps were developed into a hydrogel patch to eradicate acne-inducing bacteria. Experimental procedure: The G. mangostana extract was investigated for bactericidal activity. A hydrogel patch containing the extract was examined for mechanical properties, antibacterial activity, in vitro release, skin permeation, and a phase I clinical study of skin irritation and allergic testing by a closed patch test. Finding/Results: The G. mangostana hydrogel patch made from carrageenan and locust bean gum powders was yellow in color, smooth, durable, and flexible. This G. mangostana hydrogel patch was effective against Cutibacterium acnes, Staphylococcus epidermidis, and Staphylococcus aureus. The active ingredient, α-mangostin, was released and permeated from the G. mangostana hydrogel patch within the first 30 min at 33.16 ± 0.81% and 32.96± 0.97%, respectively. The G. mangostana hydrogel patch showed no irritation in 30 healthy volunteers. However, two volunteers had delayed allergic contact dermatitis to 0.5% (w/w) G. mangostana hydrogel patch. Conclusion and implication: This hydrogel patch containing G. mangostana ethanolic extract is not recommended for patients who have any reaction to mangosteen but has utility as an anti-acne facial mask.
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Delayed wound healing in patients having type-II diabetes mellitus (T2DM) often results in a high rate of amputation. We report an innovative Guar Gum-based macroporous hydrogel (HG) infused with an antibacterial agent (Ag NPs), and antioxidant, epigallocatechin gallate (EGCG) to address rapid wound healing and interestingly could inhibit the associated pathophysical bone infection in a high-fat-diet-induced T2DM C57BL/6 mice model. The HG-Ag-EGCG elicits scar-free wound healing in subcutaneous wounds and histopathological evidence confirmed HG-Ag-EGCG hydrogel patch elicits better wound healing through enhanced cell proliferation, mature connecting tissue fiber formation, minimum void spaces formation, and better re-epithelialization when compared with a market available hydrogel patch material (Luofucon®). Supportive of the in vivo outcomes, in vitro experiments delineated better-wound closure due to improved management of ROS by the HG-Ag-EGCG. Additionally, a favorable non-toxicity outcome assessed through both in vitro and in vivo conditions confirmed its potential applicability in clinical wound care management.
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Diabetes Mellitus Tipo 2 , Prata , Animais , Catequina/análogos & derivados , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hidrogéis/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio/farmacologia , Prata/farmacologia , CicatrizaçãoRESUMO
Oral potentially malignant disorders (OPMDs) are precursor lesions with an increased risk of malignant transformation. Topical photodynamic therapy (PDT) mediated by 5-aminolevulinic acid (ALA) (ALA-PDT) is a promising therapeutic method in the treatment of OPMDs. However, the clinical application of topical ALA-PDT is restricted by several limitations, including low delivery efficiency, poor comfort, and easy influence by saliva. Here, we designed a highly adhesion-strength dry polyacrylic acid (PAA)-chitosan (CHI)-ALA interpenetrating network hydrogel (PACA) patch after investigating the spatiotemporal dynamics of ALA drug delivery via diffusion-based finite-element models. The PACA patch could adhere to the moist oral mucosa fast and stably and deliver ALA. PACA hydrogel-mediated PDT (PACA-PDT) effectively improved OPMDs in vitro and in a hamster oral carcinogenesis model. In particular, we conducted a trial to recruit 60 OPMD volunteers to demonstrate the feasibility and comfort of the PACA hydrogel patch. This study provides evidence that PACA hydrogel-mediated PDT could be a patient-friendly treatment modality for OPMDs.
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Fotoquimioterapia , Lesões Pré-Cancerosas , Ácido Aminolevulínico/uso terapêutico , Animais , Cricetinae , Humanos , Hidrogéis/uso terapêutico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Lesões Pré-Cancerosas/tratamento farmacológicoRESUMO
Bio-inspired adhesive hydrogels have been applied to cell and drug delivery systems to address various tissue defects and disorders. However, adhesive hydrogels functionalized with phenolic moieties often lack osteoconductive capacity and mechanical properties for bone regeneration. In this study, we utilized the versatile chemical interactions of phenolic moieties to overcome such limitations in bone tissue engineering efforts. Highly osteoconductive hybrid hydrogel patches were fabricated by incorporating inorganic minerals, hydroxyapatite (HAP), or whitlockite (WKT), into pyrogallol-conjugated hyaluronic acid (HA-PG). The hybrid HA-PG patches exhibited improved mechanical strength and reinforced structural/physical properties owing to additional intermolecular complexation between oxidized PG moieties and ions released from inorganic particles. The sustained release of bone morphogenetic protein-2 (BMP-2) from hybrid patches was prolonged by combination of the inherent nucleophilic affinity of oxidized PG and electrostatic interactions between inorganic particles and BMP-2. With increased osteoconductivity, hybrid patches with HAP or WKT enhanced the osteogenic differentiation of human stem cells while also promoting new bone formation in a critical-sized calvarial defect. Our study demonstrates a translational potential of phenolic adhesive hydrogels engineered with inorganic minerals for orthopedic applications.
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Hidrogéis , Osteogênese , Proteína Morfogenética Óssea 2 , Regeneração Óssea , Durapatita , Humanos , Ácido HialurônicoRESUMO
Nanotechnology driven cancer theranostics hold potential as promising future clinical modalities. Currently, there is a strong emphasis on the development of combinational modalities, especially for cancer treatment. In this study, we present a topical hydrogel patch for nanomaterial-assisted photothermal therapeutics as well as for on-demand drug delivery application. The patch was derived from interpenetrating networks (IPNs) of alginate (Alg) and polyacrylamide (PAAm) in weight ratio 8:1 by free radical polymerization. The patch interiors were composed of hybrid nanostructures derived from gold nanorods (AuNRs) anchored onto polyvinylpyrrolidone (PVP) functionalized graphene oxide (PVP-nGO) to form PVP-nGO@AuNRs hybrids. Field emission scanning electron microscopy (FE-SEM) images revealed the porous nature of the hybrid hydrogel patch with an average pore size of ~28.60 ± 3.10 µm. Besides, functional characteristics of the hybrid patch, such as mechanical strength, viscoelastic and swelling behavior, were investigated. Under near-infrared (NIR) radiation exposure, the hybrid patch exhibited photothermal properties such as surface temperature rise to 75.16 ± 0.32 °C, sufficient to ablate cancer cells thermally. Besides, the heat generated in the hybrid patch could be transmitted to an underlying hydrogel (mimicking skin tissue) when stacked together without much loss. Under cyclic photothermal heating, the patch could retain its photothermal stability for four cycles. Furthermore, the hybrid patch demonstrated NIR stimulated drug release, which was evaluated using methotrexate (MTX, water-insoluble anticancer drug) and rhodamine B (RhB, water-soluble dye). Taken together, this work provides a new dimension towards the development of externally placed hydrogel patches for thermal destruction of localized solid tumors and tunable delivery of chemotherapeutic drugs at the target site.
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Portadores de Fármacos/química , Hidrogéis/química , Raios Infravermelhos , Alginatos/química , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Ouro/química , Grafite/química , Metotrexato/química , Metotrexato/metabolismo , Nanoestruturas/química , Nanotubos/química , Povidona/química , Reologia , Rodaminas/química , Rodaminas/metabolismo , TemperaturaRESUMO
Over the past decade, tissue-engineering strategies, mainly involving injectable hydrogels and epicardial biomaterial patches, have been pursued to treat myocardial infarction. However, only limited therapeutic efficacy is achieved with a single means. Here, a combined therapy approach is proposed, that is, the coadministration of a conductive hydrogel patch and injectable hydrogel to the infarcted myocardium. The self-adhesive conductive hydrogel patch is fabricated based on Fe3+-induced ionic coordination between dopamine-gelatin (GelDA) conjugates and dopamine-functionalized polypyrrole (DA-PPy), which form a homogeneous network. The injectable and cleavable hydrogel is formed in situ via a Schiff base reaction between oxidized sodium hyaluronic acid (HA-CHO) and hydrazided hyaluronic acid (HHA). Compared with a single-mode system, injecting the HA-CHO/HHA hydrogel intramyocardially followed by painting a conductive GelDA/DA-PPy hydrogel patch on the heart surface results in a more pronounced improvement of the cardiac function in terms of echocardiographical, histological, and angiogenic outcomes.