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1.
ACS Biomater Sci Eng ; 10(7): 4425-4436, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38597148

RESUMEN

Traditional Chinese medicine external prescriptions have displayed excellent clinical effects for treating deep soft tissue injuries. However, the effects cannot be fully utilized due to the limitations of their dosage forms and usage methods. It is still a challenge to develop a satisfactory adjuvant of traditional Chinese medicine external prescriptions. Herein, a hydrogel adjuvant was prepared based on gallic acid coupled ε-poly-l-lysine and partially oxidized hyaluronic acid. The resulting adjuvant shows great physicochemical properties, low hemolysis rate (still much less than 5% at 5 mg/mL), excellent antibacterial ability (about 95% at 2 mg/mL), strong antioxidant ability (1.687 ± 0.085 mmol FeSO4/(g hydrogel) at 1 mg/mL), as well as outstanding biocompatibility. A clinically used Chinese medicine external preparation was selected as an example to investigate the effectiveness of the adjuvant in treating deep soft tissue injuries. The results show that the prescription can be evenly dispersed in the adjuvant. Moreover, the introduction of the prescription has not significantly changed these advanced properties of the adjuvant. Importantly, the hydrogel adjuvant significantly improves the effectiveness of the prescription in treating deep soft tissue injuries. This work offers an alternative approach to the development of a new-type adjuvant of Chinese medicine external preparations and also provides a new strategy for the combination of traditional Chinese medicine and hydrogel to treat clinical diseases.


Asunto(s)
Medicamentos Herbarios Chinos , Hidrogeles , Traumatismos de los Tejidos Blandos , Cicatrización de Heridas , Hidrogeles/química , Hidrogeles/farmacología , Hidrogeles/uso terapéutico , Animales , Cicatrización de Heridas/efectos de los fármacos , Traumatismos de los Tejidos Blandos/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Ácido Hialurónico/química , Ácido Hialurónico/uso terapéutico , Ácido Hialurónico/farmacología , Medicina Tradicional China , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Antibacterianos/química , Ácido Gálico/química , Ácido Gálico/farmacología , Ácido Gálico/uso terapéutico , Polilisina/química , Polilisina/farmacología , Polilisina/uso terapéutico , Humanos , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Hemólisis/efectos de los fármacos , Ratones
2.
J Mater Chem B ; 12(19): 4629-4641, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38666407

RESUMEN

Enlightened by the great success of the drug repurposing strategy in the pharmaceutical industry, in the current study, material repurposing is proposed where the performance of carbonyl iron powder (CIP), a nutritional intervention agent of iron supplement approved by the US FDA for iron deficiency anemia in clinic, was explored in anti-cancer treatment. Besides the abnormal iron metabolic characteristics of tumors, serving as potential targets for CIP-based cancer therapy under the repurposing paradigm, the efficacy of CIP as a catalyst in the Fenton reaction, activator for dihydroartemisinin (DHA), thus increasing the chemo-sensitivity of tumors, as well as a potent agent for NIR-II photothermal therapy (PTT) was fully evaluated in an injectable alginate hydrogel form. The CIP-ALG gel caused a rapid temperature rise in the tumor site under NIR-II laser irradiation, leading to complete ablation in the primary tumor. Further, this photothermal-ablation led to the significant release of ATP, and in the bilateral tumor model, both primary tumor ablation and inhibition of secondary tumor were observed simultaneously under the synergistic tumor treatment of nutritional-photothermal therapy (NT/PTT). Thus, material repurposing was confirmed by our pioneering trial and CIP-ALG-meditated NT/PTT/immunotherapy provides a new choice for safe and efficient tumor therapy.


Asunto(s)
Adenosina Trifosfato , Antineoplásicos , Rayos Infrarrojos , Animales , Adenosina Trifosfato/metabolismo , Adenosina Trifosfato/química , Ratones , Antineoplásicos/farmacología , Antineoplásicos/química , Inmunoterapia , Reposicionamiento de Medicamentos , Humanos , Rayos Láser , Terapia Fototérmica , Ratones Endogámicos BALB C , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Alginatos/química , Femenino , Hidrogeles/química , Hidrogeles/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Tamaño de la Partícula , Artemisininas/química , Artemisininas/farmacología
3.
J Mater Chem B ; 12(18): 4409-4426, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38630533

RESUMEN

Spinal cord injury (SCI) usually induces profound microvascular dysfunction. It disrupts the integrity of the blood-spinal cord barrier (BSCB), which could trigger a cascade of secondary pathological events that manifest as neuronal apoptosis and axonal demyelination. These events can further lead to irreversible neurological impairments. Thus, reducing the permeability of the BSCB and maintaining its substructural integrity are essential to promote neuronal survival following SCI. Tetramethylpyrazine (TMP) has emerged as a potential protective agent for treating the BSCB after SCI. However, its therapeutic potential is hindered by challenges in the administration route and suboptimal bioavailability, leading to attenuated clinical outcomes. To address this challenge, traditional Chinese medicine, TMP, was used in this study to construct a drug-loaded electroconductive hydrogel for synergistic treatment of SCI. A conductive hydrogel combined with TMP demonstrates good electrical and mechanical properties as well as superior biocompatibility. Furthermore, it also facilitates sustained local release of TMP at the implantation site. Furthermore, the TMP-loaded electroconductive hydrogel could suppress oxidative stress responses, thereby diminishing endothelial cell apoptosis and the breakdown of tight junction proteins. This concerted action repairs BSCB integrity. Concurrently, myelin-associated axons and neurons are protected against death, which meaningfully restore neurological functions post spinal cord injury. Hence, these findings indicate that combining the electroconductive hydrogel with TMP presents a promising avenue for potentiating drug efficacy and synergistic repair following SCI.


Asunto(s)
Hidrogeles , Neuronas , Pirazinas , Traumatismos de la Médula Espinal , Pirazinas/química , Pirazinas/farmacología , Traumatismos de la Médula Espinal/tratamiento farmacológico , Hidrogeles/química , Hidrogeles/farmacología , Hidrogeles/síntesis química , Animales , Neuronas/efectos de los fármacos , Ratas Sprague-Dawley , Ratas , Médula Espinal/efectos de los fármacos , Conductividad Eléctrica , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/farmacología , Ratones , Apoptosis/efectos de los fármacos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología
4.
J Mater Chem B ; 12(17): 4148-4161, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38591180

RESUMEN

Cyaonoside A (CyA), derived from the natural Chinese medicine, Cyathula officinalis Kuan, which was for a long time used to treat knee injuries and relieve joint pain in traditional Chinese medicine, showed an unclear mechanism for protecting cartilage. In addition, CyA was poorly hydrosoluble and incapable of being injected directly into the joint cavity, which limited its clinical application. This study reveals that CyA resisted IL-1ß-mediated chondrogenic inflammation and apoptosis. Next, transcriptome sequencing is used to explore the potential mechanisms underlying CyA regulation of MSC chondrogenic differentiation. Based on these findings, CyA-loaded composite hydrogel microspheres (HLC) were developed and they possessed satisfactory loading efficiency, a suitable degradation rate and good biocompatibility. HLC increased chondrogenic anabolic gene (Acan, COL2A, and SOX9) expression, while downregulating the expression of the catabolic marker MMP13 in vitro. In the osteoarthritis mouse model, HLC demonstrated promising therapeutic capabilities by protecting the integrity of articular cartilage. In conclusion, this study provides insights into the regulatory mechanisms of CyA for chondrocytes and proposes a composite hydrogel microsphere-based advanced therapeutic strategy for osteoarthritis.


Asunto(s)
Condrocitos , Hidrogeles , Microesferas , Osteoartritis , Condrocitos/efectos de los fármacos , Condrocitos/metabolismo , Animales , Hidrogeles/química , Hidrogeles/farmacología , Osteoartritis/tratamiento farmacológico , Osteoartritis/patología , Ratones , Inflamación/tratamiento farmacológico , Ratones Endogámicos C57BL , Masculino , Tamaño de la Partícula , Células Cultivadas
5.
Nanoscale ; 16(17): 8378-8389, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38602041

RESUMEN

Bacterial infection is one of the most serious clinical complications, with life-threatening outcomes. Nature-inspired biomaterials offer appealing microscale and nanoscale architectures that are often hard to fabricate by traditional technologies. Inspired by the light-harvesting nature, we engineered sulfuric acid-treated sunflower sporopollenin exine-derived microcapsules (HSECs) to capture light and bacteria for antimicrobial photothermal therapy. Sulfuric acid-treated HSECs show a greatly enhanced photothermal performance and a strong bacteria-capturing ability against Gram-positive bacteria. This is attributed to the hierarchical micro/nanostructure and surface chemistry alteration of HSECs. To test the potential for clinical application, an in situ bacteria-capturing, near-infrared (NIR) light-triggered hydrogel made of HSECs and curdlan is applied in photothermal therapy for infected skin wounds. HSECs and curdlan suspension that spread on bacteria-infected skin wounds of mice first capture the local bacteria and then form hydrogels on the wound upon NIR light stimulation. The combination shows a superior antibacterial efficiency of 98.4% compared to NIR therapy alone and achieved a wound healing ratio of 89.4%. The current study suggests that the bacteria-capturing ability and photothermal properties make HSECs an excellent platform for the phototherapy of bacteria-infected diseases. Future work that can fully take advantage of the hierarchical micro/nanostructure of HSECs for multiple biomedical applications is highly promising and desirable.


Asunto(s)
Biopolímeros , Cápsulas , Carotenoides , Helianthus , Terapia Fototérmica , Polen , Animales , Ratones , Helianthus/química , Polen/química , Cápsulas/química , Antibacterianos/química , Antibacterianos/farmacología , Hidrogeles/química , Hidrogeles/farmacología , Staphylococcus aureus/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos , Rayos Infrarrojos
6.
Nano Lett ; 24(15): 4649-4657, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38572971

RESUMEN

Deep-seated bacterial infections (DBIs) are stubborn and deeply penetrate tissues. Eliminating deep-seated bacteria and promoting tissue regeneration remain great challenges. Here, a novel radical-containing hydrogel (SFT-B Gel) cross-linked by a chaotropic effect was designed for the sensing of DBIs and near-infrared photothermal therapy (NIR-II PTT). A silk fibroin solution stained with 4,4',4″-(1,3,5-triazine-2,4,6-triyl)tris(1-methylpyridin-1-ium) (TPT3+) was employed as the backbone, which could be cross-linked by a closo-dodecaborate cluster (B12H122-) through a chaotropic effect to form the SFT-B Gel. More interestingly, the SFT-B Gel exhibited the ability to sense DBIs, which could generate a TPT2+• radical with obvious color changes in the presence of bacteria. The radical-containing SFT-B Gel (SFT-B★ Gel) possessed strong NIR-II absorption and a remarkable photothermal effect, thus demonstrating excellent NIR-II PTT antibacterial activity for the treatment of DBIs. This work provides a new approach for the construction of intelligent hydrogels with unique properties using a chaotropic effect.


Asunto(s)
Fototerapia , Terapia Fototérmica , Hidrogeles/farmacología
7.
Adv Healthc Mater ; 13(16): e2303314, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38558386

RESUMEN

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.


Asunto(s)
Diabetes Mellitus Experimental , Hidrogeles , Oxígeno , Peróxidos , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Animales , Hidrogeles/química , Hidrogeles/farmacología , Ratones , Oxígeno/química , Peróxidos/química , Peróxidos/farmacología , Humanos , Polietilenglicoles/química , Neovascularización Fisiológica/efectos de los fármacos , Masculino , Células Endoteliales de la Vena Umbilical Humana , Movimiento Celular/efectos de los fármacos
8.
Adv Healthc Mater ; 13(19): e2400071, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38501563

RESUMEN

The treatment of infected wounds remains a challenging biomedical problem. Some bioactive small-molecule hydrogelators with unique rigid structures can self-assemble into supramolecular hydrogels for wound healing. However, they are still suffered from low structural stability and bio-functionality. Herein, a supramolecular hydrogel antibacterial dressing with a dual nanofibrillar network structure is proposed. A nanofibrillar network created by a small-molecule hydrogelator, puerarin extracted from the traditional Chinese medicine Pueraria, is interconnected with a secondary macromolecular silk fibroin nanofibrillar network induced by Ga ions via charge-induced supramolecular self-assembly. The resulting hydrogel features adequate mechanical strength for sustainable retention at wounds. Good biocompatibility and efficient bacterial inhibition are obtained when the Ga ion concentration is 0.05%. Otherwise, the substantial release of Ga ions and puerarin endows the hydrogel with excellent hemostatic and antioxidative properties. In vivo, evaluation of a mouse-infected wound model demonstrates that its healing effect outperformed that of a commercially available silver-containing wound dressing. The experimental group successfully achieves a 100% wound closure rate on day 10. This study sheds new light on the design of nanofibrillar hydrogels based on supramolecular self-assembly of naturally derived bioactive molecules as well as their clinical use for treating chronic infected wounds.


Asunto(s)
Fibroínas , Hidrogeles , Isoflavonas , Nanofibras , Cicatrización de Heridas , Fibroínas/química , Animales , Isoflavonas/química , Isoflavonas/farmacología , Hidrogeles/química , Hidrogeles/farmacología , Ratones , Cicatrización de Heridas/efectos de los fármacos , Nanofibras/química , Antibacterianos/química , Antibacterianos/farmacología , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Vendajes , Masculino , Staphylococcus aureus/efectos de los fármacos
9.
Biomed Pharmacother ; 173: 116389, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38461682

RESUMEN

Staphylococcus aureus is one of the most common bacterial isolates found in wounds. Thus, innovative dressings, such as hydrogels, are interesting vehicles for incorporating bioactive compounds like those from Melaleuca alternifolia essential oil (MaEO). In this study, we evaluated the antimicrobial and anti-inflammatory potential of MaEO incorporated into an alginate and chitosan hydrogel for treating wounds infected by S. aureus. The hydrogel incorporated with MaEO 1% (HMa 1%) was homogeneous with a bright pale-yellow color and the characteristic smell of Melaleuca. The incorporation of MaEO 1% does not affect the stability of the hydrogel, which was stable up to 90 days of storage. The Scanning electron microscopy analysis revealed that hydrogels showed irregular surfaces and interconnected porous structures with accumulations of oil crystals distributed throughout the formulation. HMa 1% has a high moisture content (95.1%) and can absorb simulated wound fluid. Regarding the antimicrobial effects, HMa 1% reduced the growth of S. aureus ATCC 6538 in both in vitro conditions and in an ex vivo model of wounds using porcine skin. In addition, the dairy topical treatment of murine skin lesions with HMa 1% induced a significant reduction of the wound area, inflammation score, and bacterial load, as well as tissue re-epithelialization and modulation of inflammatory mediators. Therefore, hydrogel incorporated with MaEO 1% has excellent potential to be used in the pharmacotherapy of infected wounds.


Asunto(s)
Antiinfecciosos , Melaleuca , Aceites Volátiles , Infecciones Estafilocócicas , Aceite de Árbol de Té , Porcinos , Animales , Ratones , Staphylococcus aureus , Aceites Volátiles/farmacología , Aceites Volátiles/uso terapéutico , Aceites Volátiles/química , Melaleuca/química , Hidrogeles/farmacología , Hidrogeles/uso terapéutico , Antiinfecciosos/farmacología , Infecciones Estafilocócicas/tratamiento farmacológico , Aceite de Árbol de Té/farmacología , Aceite de Árbol de Té/uso terapéutico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico
10.
ACS Appl Mater Interfaces ; 16(13): 16011-16028, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38529951

RESUMEN

Superbug infections and transmission have become major challenges in the contemporary medical field. The development of novel antibacterial strategies to efficiently treat bacterial infections and conquer the problem of antimicrobial resistance (AMR) is extremely important. In this paper, a bimetallic CuCo-doped nitrogen-carbon nanozyme-functionalized hydrogel (CuCo/NC-HG) has been successfully constructed. It exhibits photoresponsive-enhanced enzymatic effects under near-infrared (NIR) irradiation (808 nm) with strong peroxidase (POD)-like and oxidase (OXD)-like activities. Upon NIR irradiation, CuCo/NC-HG possesses photodynamic activity for producing singlet oxygen(1O2), and it also has a high photothermal conversion effect, which not only facilitates the elimination of bacteria but also improves the efficiency of reactive oxygen species (ROS) production and accelerates the consumption of GSH. CuCo/NC-HG shows a lower hemolytic rate and better cytocompatibility than CuCo/NC and possesses a positive charge and macroporous skeleton for restricting negatively charged bacteria in the range of ROS destruction, strengthening the antibacterial efficiency. Comparatively, CuCo/NC and CuCo/NC-HG have stronger bactericidal ability against methicillin-resistant Staphylococcus aureus (MRSA) and ampicillin-resistant Escherichia coli (AmprE. coli) through destroying the cell membranes with a negligible occurrence of AMR. More importantly, CuCo/NC-HG plus NIR irradiation can exhibit satisfactory bactericidal performance in the absence of H2O2, avoiding the toxicity from high-concentration H2O2. In vivo evaluation has been conducted using a mouse wound infection model and histological analyses, and the results show that CuCo/NC-HG upon NIR irradiation can efficiently suppress bacterial infections and promote wound healing, without causing inflammation and tissue adhesions.


Asunto(s)
Infecciones Bacterianas , Staphylococcus aureus Resistente a Meticilina , Animales , Hidrogeles/farmacología , Escherichia coli , Peróxido de Hidrógeno , Especies Reactivas de Oxígeno , Fototerapia , Infecciones Bacterianas/tratamiento farmacológico , Antibacterianos/farmacología , Carbono , Modelos Animales de Enfermedad , Nitrógeno
11.
Biomater Adv ; 159: 213838, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38531257

RESUMEN

The process of wound healing necessitates a specific environment, thus prompting extensive research into the utilization of hydrogels for this purpose. While numerous hydrogel structures have been investigated, the discovery of a self-healing hydrogel possessing favorable biocompatibility, exceptional mechanical properties, and effective hemostatic and antibacterial performance remains uncommon. In this work, a polyvinyl alcohol (PVA) hybrid hydrogel was meticulously designed through a simple reaction, wherein CuxO anchored sepiolite was incorporated into the hydrogel. The results indicate that introduction of sepiolite greatly improves the toughness, self-healing and adhesion properties of the PVA hydrogels. CuxO nanoparticles endow the hydrogels with excellent antibacterial performance towards Staphylococcus aureus and Escherichia coli. The application of hybrid hydrogels for fast hemostasis and wound healing are verified in vitro and in vivo with rat experiments. This work thereby demonstrates an effective strategy for designing biodegradable hemostatic and wound healing materials.


Asunto(s)
Esencias Florales , Hemostáticos , Silicatos de Magnesio , Prunella , Animales , Ratas , Hidrogeles/farmacología , Hemostáticos/farmacología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Escherichia coli , Cicatrización de Heridas , Hemostasis
12.
Carbohydr Polym ; 334: 122068, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38553197

RESUMEN

The fabrication of highly elastic, fatigue-resistant and conductive hydrogels with antibacterial properties is highly desirable in the field of wearable devices. However, it remains challenging to simultaneously realize the above properties within one hydrogel without compromising excellent sensing ability. Herein, we fabricated a highly elastic, fatigue-resistant, conductive, antibacterial and cellulose nanocrystal (CNC) enhanced hydrogel as a sensitive strain sensor by the synergistic effect of biosynthesized selenium nanoparticles (BioSeNPs), MXene and nanocellulose. The structure and potential mechanism to generate biologically synthesized SeNPs (BioSeNPs) were systematically investigated, and the role of protease A (PrA) in enhancing the adsorption between proteins and SeNPs was demonstrated. Additionally, owing to the incorporation of BioSeNPs, CNC and MXene, the synthesized hydrogels showed high elasticity, excellent fatigue resistance and antibacterial properties. More importantly, the sensitivity of hydrogels determined by the gauge factor was as high as 6.24 when a high strain was applied (400-700 %). This study provides a new horizon to synthesize high-performance antibacterial and conductive hydrogels for soft electronics applications.


Asunto(s)
Nanopartículas , Nitritos , Selenio , Elementos de Transición , Antibacterianos/farmacología , Celulosa/farmacología , Conductividad Eléctrica , Hidrogeles/farmacología
13.
Int J Biol Macromol ; 264(Pt 1): 130477, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38428784

RESUMEN

Multidrug-resistant (MDR) bacterial infections have become a significant threat to global healthcare systems. Here, we developed a highly efficient antimicrobial hydrogel using environmentally friendly garlic carbon dots, pectin, and acrylic acid. The hydrogel had a porous three-dimensional network structure, which endowed it with good mechanical properties and compression recovery performance. The hydrogel could adhere closely to skin tissues and had an equilibrium swelling ratio of 6.21, indicating its potential as a wound dressing. In particular, the bactericidal efficacy following 24-h contact against two MDR bacteria could exceed 99.99 %. When the hydrogel was applied to epidermal wounds infected with methicillin-resistant Staphylococcus aureus (MRSA) on mice, a remarkable healing rate of 93.29 % was observed after 10 days. This was better than the effectiveness of the traditionally used antibiotic kanamycin, which resulted in a healing rate of 70.36 %. In vitro cytotoxicity testing and hemolysis assay demonstrated a high biocompatibility. This was further proved by the in vivo assay where no toxic side effects were observed on the heart, liver, spleen, lung, or kidney of mice. This eco-friendly and easy-to-prepare food-inspired hydrogel provides an idea for the rational use of food and food by-products as a wound dressing to control MDR bacterial infections.


Asunto(s)
Antiinfecciosos , Infecciones Bacterianas , Staphylococcus aureus Resistente a Meticilina , Ratones , Animales , Carbono/química , Hidrogeles/farmacología , Hidrogeles/química , Pectinas/farmacología , Antiinfecciosos/farmacología , Antibacterianos/química , Infecciones Bacterianas/tratamiento farmacológico
14.
Cell Prolif ; 57(7): e13613, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38351579

RESUMEN

Diabetic wounds impose significant burdens on patients' quality of life and healthcare resources due to impaired healing potential. Factors like hyperglycemia, oxidative stress, impaired angiogenesis and excessive inflammation contribute to the delayed healing trajectory. Mounting evidence indicates a close association between impaired mitochondrial function and diabetic complications, including chronic wounds. Mitochondria are critical for providing energy essential to wound healing processes. However, mitochondrial dysfunction exacerbates other pathological factors, creating detrimental cycles that hinder healing. This study conducted correlation analysis using clinical specimens, revealing a positive correlation between mitochondrial dysfunction and oxidative stress, inflammatory response and impaired angiogenesis in diabetic wounds. Restoring mitochondrial function becomes imperative for developing targeted therapies. Herein, we synthesized a biodegradable poly (glycerol sebacate)-based multiblock hydrogel, named poly (glycerol sebacate)-co-poly (ethylene glycol)-co-poly (propylene glycol) (PEPGS), which can be degraded in vivo to release glycerol, a crucial component in cellular metabolism, including mitochondrial respiration. We demonstrate the potential of PEPGS-based hydrogels to improve outcomes in diabetic wound healing by revitalizing mitochondrial metabolism. Furthermore, we investigate the underlying mechanism through proteomics analysis, unravelling the regulation of ATP and nicotinamide adenine dinucleotide metabolic processes, biosynthetic process and generation during mitochondrial metabolism. These findings highlight the therapeutic potential of PEPGS-based hydrogels as advanced wound dressings for diabetic wound healing.


Asunto(s)
Decanoatos , Glicerol , Hidrogeles , Mitocondrias , Polímeros , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Glicerol/química , Glicerol/metabolismo , Glicerol/análogos & derivados , Hidrogeles/química , Hidrogeles/farmacología , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Decanoatos/química , Decanoatos/farmacología , Humanos , Animales , Polímeros/química , Polímeros/farmacología , Masculino , Estrés Oxidativo/efectos de los fármacos , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Ratones , Femenino , Polietilenglicoles/química , Polietilenglicoles/farmacología
15.
J Nanobiotechnology ; 22(1): 80, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38418972

RESUMEN

The advancement of biomaterials with antimicrobial and wound healing properties continues to present challenges. Macrophages are recognized for their significant role in the repair of infection-related wounds. However, the interaction between biomaterials and macrophages remains complex and requires further investigation. In this research, we propose a new sequential immunomodulation method to enhance and expedite wound healing by leveraging the immune properties of bacteria-related wounds, utilizing a novel mixed hydrogel dressing. The hydrogel matrix is derived from porcine acellular dermal matrix (PADM) and is loaded with a new type of bioactive glass nanoparticles (MBG) doped with magnesium (Mg-MBG) and loaded with Curcumin (Cur). This hybrid hydrogel demonstrates controlled release of Cur, effectively eradicating bacterial infection in the early stage of wound infection, and the subsequent release of Mg ions (Mg2+) synergistically inhibits the activation of inflammation-related pathways (such as MAPK pathway, NF-κB pathway, TNF-α pathway, etc.), suppressing the inflammatory response caused by infection. Therefore, this innovative hydrogel can safely and effectively expedite wound healing during infection. Our design strategy explores novel immunomodulatory biomaterials, offering a fresh approach to tackle current clinical challenges associated with wound infection treatment.


Asunto(s)
Antiinfecciosos , Curcumina , Infección de Heridas , Animales , Porcinos , Hidrogeles/farmacología , Cicatrización de Heridas , Biomimética , Vendajes , Antibacterianos/uso terapéutico , Materiales Biocompatibles , Inmunoterapia , Infección de Heridas/tratamiento farmacológico
16.
ACS Appl Mater Interfaces ; 16(8): 9749-9767, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38359334

RESUMEN

The treatment of diabetic chronic wounds is still faced with great challenges, mainly due to wound infection, excessive inflammation, and peripheral vascular disease in the wound area. Therefore, it is of great importance to develop a novel multifunctional hydrogel with high efficiency to accelerate diabetic wound healing. Curcumin (Cur), a Chinese herbal, has shown great potential in enhancing the healing of diabetic chronic wounds because of its immunomodulatory and pro-angiogenic properties. However, its low aqueous solubility, poor bioavailability, and chemical instability have limited its clinical applications. To address these current bottlenecks, novel poly(vinyl alcohol) (PVA)-chitosan (CS)/sodium alginate (SA)-Cur (PCSA) hydrogels were prepared for the first time, and they demonstrated all of the above intriguing performances by the Michael addition reaction of CS and Cur. PCSA hydrogels show multiple dynamic bonds, which possess strong mechanical properties (tensile stress: ∼0.980 MPa; toughness: ∼258.45 kJ/m3; and compressive strength: ∼7.38 MPa at strain of 80%). These intriguing performances provided an optimal microenvironment for cell migration and proliferation and also promoted the growth of blood vessels, leading to early angiogenesis. Importantly, the experimental results demonstrated that PCSA hydrogels can effectively transform pro-inflammatory M1 macrophages into anti-inflammatory M2 macrophages without the need for additional ingredients in vitro. Benefiting from these characteristics, a full-thickness diabetic wound in a rat model demonstrated that PCSA hydrogels can effectively accelerate wound healing via ROS-scavenging, downregulation of IL-1ß, and upregulation of CD31 expression, resulting in angiogenesis and collagen deposition. This strategy not only provides a simple and safe Cur-based hydrogel for diabetic wound healing but also highlights the significant potential for the development of high-performance biomaterials for promoting diabetic wound healing using traditional Chinese medicine.


Asunto(s)
Antiinfecciosos , Quitosano , Curcumina , Diabetes Mellitus , Ratas , Animales , Hidrogeles/farmacología , Hidrogeles/química , Curcumina/química , Antioxidantes/farmacología , Angiogénesis , Cicatrización de Heridas , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antiinfecciosos/farmacología , Quitosano/farmacología , Antibacterianos/química
17.
ACS Appl Mater Interfaces ; 16(8): 9656-9668, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38377529

RESUMEN

Wound infection and tumor recurrence are the two main threats to cancer patients after surgery. Although researchers have developed new treatment systems to address the two significant challenges simultaneously, the potential side effects of the heavy-metal-ion-based treatment systems still severely limit their widespread application in therapy. In addition, the wounds from tumor removal compared with general operative wounds are more complex. The tumor wounds mainly exhibit more hemorrhage, larger trauma area, greater vulnerability to bacterial infection, and residual tumor cells. Therefore, a multifunctional treatment platform is urgently needed to integrate rapid hemostasis, sterilization, wound healing promotion, and antitumor functions. In this work, nanodiamonds (NDs), a material that has been well proven to have excellent biocompatibility, are added into a solution of acrylic-grafted chitosan (CEC) and oxidized hyaluronic acid (OHA) to construct a multifunctional treatment platform (CEC-OHA-NDs). The hydrogels exhibit rapid hemostasis, a wound-healing-promoting effect, excellent self-healing, and injectable abilities. Moreover, CEC-OHA-NDs can effectively eliminate bacteria and inhibit tumor proliferation by the warm photothermal effect of NDs under tissue-penetrable near-infrared laser irradiation (NIR) without cytotoxicity. Consequently, we adopt a simple and convenient strategy to construct a multifunctional treatment platform using carbon-based nanomaterials with excellent biocompatibility to promote the healing of infected wounds and to inhibit tumor cell proliferation simultaneously.


Asunto(s)
Terapia por Estimulación Eléctrica , Nanodiamantes , Neoplasias , Humanos , Manejo del Dolor , Fototerapia , Ácido Hialurónico , Hidrogeles/farmacología , Antibacterianos , Neoplasias/tratamiento farmacológico
18.
Int J Biol Macromol ; 262(Pt 1): 129988, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38325692

RESUMEN

Bacterial infection and oxidative stress impede clinical wound healing. Herein, the plant-derived cowberry extract (CE) was first explored as a natural photothermal agent and antioxidant to deal with bacterial infection and oxidative stress. After loading in the carboxymethyl chitosan (CMCs)/oxidized dextran (Odex) hydrogel, the photothermal effect of CE was highly enhanced by CMCs. The controlled temperature induced by CE-containing hydrogel under NIR laser irradiation could rapidly (10 min) and effectively kill Staphylococcus aureus (S. aureus, 99.3 %) and Escherichia coli (E. coli, 94.6 %). Besides, this hydrogel exhibited a fast gelation and hemostasis abilities, high stability, adhesion and ROS scavenging capabilities, as well as good injectability and biocompatibility. Above superior properties make this hydrogel to accelerate the wound healing in S. aureus-infected mice, and it is expected to be a potential clinical wound dressing.


Asunto(s)
Quitosano , Infecciones Estafilocócicas , Infección de Heridas , Animales , Ratones , Antioxidantes/farmacología , Hidrogeles/farmacología , Escherichia coli , Staphylococcus aureus , Extractos Vegetales/farmacología , Cicatrización de Heridas , Antibacterianos/farmacología
19.
Int J Biol Macromol ; 263(Pt 2): 129887, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38383251

RESUMEN

Infected wound management is a great challenge to healthcare, especially in emergencies such as accidents or battlefields. Hydrogels as wound dressings can replace or supplement traditional wound treatment strategies, such as bandages or sutures. It is significant to develop novel hydrogel-based wound dressings with simple operation, inexpensive, easy debridement, effective antibacterial, biocompatibility, etc. Here, we designed a novel gelatin-based hydrogel wound dressing Gel-TA-Fe3+. The hydrogels used tannic-modified gelatin as the main body and Fe3+ as the crosslinking agent to achieve a controllable rapid sol-gel transition. The hydrogels exhibited tough mechanical properties, excellent antibacterial ability, biocompatibility and an acceptable temperature response to near-infrared light (NIR). Moreover, the hydrogels could promote the healing process of MRSA-infected skin wound in rats. This multifunctional hydrogel was thought to have potential for emergency treatment of bacterial infected wound.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Infección de Heridas , Animales , Ratas , Gelatina/farmacología , Cicatrización de Heridas , Suplementos Dietéticos , Antibacterianos/farmacología , Hidrogeles/farmacología , Infección de Heridas/tratamiento farmacológico
20.
Adv Healthc Mater ; 13(15): e2400049, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38416676

RESUMEN

Wound healing and infection remain significant challenges due to the ineffectiveness against multidrug-resistant (MDR) bacteria and the complex oxidative wound microenvironments. To address these issues, thymoquinone-reinforced injectable and thermosensitive TQ@PEG-PAF-Cur hydrogels with dual functions of microenvironment reshaping and photodynamic therapy are developed. The hydrogel comprises natural compound thymoquinone (TQ) and poly (ethylene glycol)-block-poly (alanine-co-phenyl alanine) copolymers (PEG-PAF) conjugated with natural photosensitizer curcumin (Cur). The incorporation of TQ and Cur reduces the sol-to-gel transition temperature of TQ@PEG-PAF-Cur to 30°C, compared to PEG-PAF hydrogel (37°C), due to the formation of strong hydrogen bonding, matching the wound microenvironment temperature. Under blue light excitation, TQ@PEG-PAF-Cur generates significant amounts of reactive oxygen species such as H2O2, 1O2, and ·OH, exhibiting rapid and efficient bactericidal capacities against methicillin-resistant Staphylococcus aureus and broad spectrum ß-lactamases Escherichia coli via photodynamic therapy (PDT). Additionally, Cur effectively inhibits the expressions of proinflammatory cytokines in skin tissue-forming cells. As a result, the composite hydrogel can rapidly transform into a gel to cover the wound, reshape the wound microenvironment, and accelerate wound healing in vivo. This collaborative antibacterial strategy provides valuable insights to guide the development of multifunctional materials for efficient wound healing.


Asunto(s)
Curcumina , Farmacorresistencia Bacteriana Múltiple , Hidrogeles , Staphylococcus aureus Resistente a Meticilina , Cicatrización de Heridas , Hidrogeles/química , Hidrogeles/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Curcumina/farmacología , Curcumina/química , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Fotoquimioterapia/métodos , Antibacterianos/farmacología , Antibacterianos/química , Polietilenglicoles/química , Polietilenglicoles/farmacología , Ratones , Escherichia coli/efectos de los fármacos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Especies Reactivas de Oxígeno/metabolismo , Fototerapia/métodos , Humanos
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