Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 63
Filtrar
1.
Proc Natl Acad Sci U S A ; 119(41): e2206684119, 2022 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-36191194

RESUMO

Leaf photosynthesis, coral mineralization, and trabecular bone growth depend on triply periodic minimal surfaces (TPMSs) with hyperboloidal structure on every surface point with varying Gaussian curvatures. However, translation of this structure into tissue-engineered bone grafts is challenging. This article reports the design and fabrication of high-resolution three-dimensional TPMS scaffolds embodying biomimicking hyperboloidal topography with different Gaussian curvatures, composed of body inherent ß-tricalcium phosphate, by stereolithography-based three-dimensional printing and sintering. The TPMS bone scaffolds show high porosity and interconnectivity. Notably, compared with conventional scaffolds, they can reduce stress concentration, leading to increased mechanical strength. They are also found to support the attachment, proliferation, osteogenic differentiation, and angiogenic paracrine function of human mesenchymal stem cells (hMSCs). Through transcriptomic analysis, we theorize that the hyperboloid structure induces cytoskeleton reorganization of hMSCs, expressing elongated morphology on the convex direction and strengthening the cytoskeletal contraction. The clinical therapeutic efficacy of the TPMS scaffolds assessed by rabbit femur defect and mouse subcutaneous implantation models demonstrate that the TPMS scaffolds augment new bone formation and neovascularization. In comparison with conventional scaffolds, our TPMS scaffolds successfully guide the cell fate toward osteogenesis through cell-level directional curvatures and demonstrate drastic yet quantifiable improvements in bone regeneration.


Assuntos
Osteogênese , Alicerces Teciduais , Animais , Regeneração Óssea , Diferenciação Celular , Humanos , Camundongos , Porosidade , Impressão Tridimensional , Coelhos , Engenharia Tecidual/métodos , Alicerces Teciduais/química
2.
J Am Chem Soc ; 143(37): 15427-15439, 2021 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-34516125

RESUMO

Traditional surgical intervention and antibiotic treatment are poor and even invalid for chronic diseases including periodontitis induced by diverse oral pathogens, which often causes progressive destruction of tissues, even tooth loss, and systemic diseases. Herein, an ointment comprising atomic-layer Fe2O3-modified two-dimensional porphyrinic metal-organic framework (2D MOF) nanosheets is designed by incorporating a polyethylene glycol matrix. After the atomic layer deposition surface engineering, the enhanced photocatalytic activity of the 2D MOF heterointerface results from lower adsorption energy and more charge transfer amounts due to the synergistic effect of metal-linker bridging units, abundant active sites, and an excellent light-harvesting network. This biocompatible and biodegradable 2D MOF-based heterostructure exhibits broad-spectrum antimicrobial activity (99.87 ± 0.09%, 99.57 ± 0.21%, and 99.03 ± 0.24%) against diverse oral pathogens (Porphyromonas gingivalis, Fusobacterium nucleatum, and Staphylococcus aureus) by the synergistic effect of reactive oxygen species and released ions. This photodynamic ion therapy exhibits a superior therapeutic effect to the reported clinical periodontitis treatment owing to rapid antibacterial activity, alleviative inflammation, and improved angiogenesis.


Assuntos
Estruturas Metalorgânicas , Periodontite/terapia , Fotoquimioterapia/métodos , Catálise , Fusobacterium nucleatum , Humanos , Nanoestruturas , Periodontite/microbiologia , Fotólise , Porphyromonas gingivalis , Staphylococcus aureus
3.
Small ; 15(22): e1900322, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31021489

RESUMO

One of the most difficult challenges in the biomedical field is bacterial infection, which causes tremendous harm to human health. In this work, an injectable hydrogel is synthesized through rapid assembly of dopamine (DA) and folic acid (FA) cross-linked by transition metal ions (TMIs, i.e., Zn2+ ), which was named as DFT-hydrogel. Both the two carboxyl groups in the FA molecule and catechol in polydopamine (PDA) easily chelates Zn2+ to form metal-ligand coordination, thereby allowing this injectable hydrogel to match the shapes of wounds. In addition, PDA in the hydrogel coated around carbon quantum dot-decorated ZnO (C/ZnO) nanoparticles (NPs) to rapidly generate reactive oxygen species (ROS) and heat under illumination with 660 and 808 nm light, endows this hybrid hydrogel with great antibacterial efficacy against Staphylococcus aureus (S. aureus, typical Gram-positive bacteria) and Escherichia coli (E. coli, typical Gram-negative bacteria). The antibacterial efficacy of the prepared DFT-C/ZnO-hydrogel against S. aureus and E. coli under dual-light irradiation is 99.9%. Importantly, the hydrogels release zinc ions over 12 days, resulting in a sustained antimicrobial effect and promoted fibroblast growth. Thus, this hybrid hydrogel exhibits great potential for the reconstruction of bacteria-infected tissues, especially exposed wounds.


Assuntos
Carbono/química , Ácido Fólico/química , Hidrogéis/química , Hidrogéis/farmacologia , Pontos Quânticos/química , Óxido de Zinco/química , Animais , Permeabilidade da Membrana Celular , Dopamina/química , Escherichia coli/efeitos dos fármacos , Camundongos , Células NIH 3T3 , Espectroscopia Fotoeletrônica , Espécies Reativas de Oxigênio/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Cicatrização/efeitos dos fármacos
4.
Small ; 14(21): e1704347, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29682895

RESUMO

Developing in situ disinfection methods in vivo to avoid drug-resistant bacteria and tissue toxicity is an urgent need. Here, the photodynamic and photothermal properties of the chitosan-assisted MoS2 (CS@MoS2 ) hybrid coating are simultaneously inspired to endow metallic Ti implants with excellent surface self-antibacterial capabilities. This coating, irradiated by only 660 nm visible light (VL) for 10 min, exhibits an antibacterial efficacy of 91.58% and 92.52% against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), respectively. The corresponding value is 64.67% and 57.44%, respectively, after irradiation by a single 808 nm near infrared light for the same amount of time. However, the combined irradiation using both lights can significantly enhance the efficiency up to 99.84% and 99.65% against E. coli and S. aureus, respectively, which can be ascribed to the synergistic effects of photodynamic and photothermal actions. The former produces single oxygen species under 660 nm VL while the latter induces a rise in temperature of implants, which can inhibit the growth of both E. coli and S. aureus. The introduction of CS can also promote the biocompatibility of implants, which provides a facile, rapid, and safe in situ bacteria-killing method in vivo without needing a second surgery.


Assuntos
Quitosana/farmacologia , Materiais Revestidos Biocompatíveis/farmacologia , Dissulfetos/farmacologia , Eletroforese , Luz , Viabilidade Microbiana/efeitos dos fármacos , Viabilidade Microbiana/efeitos da radiação , Molibdênio/farmacologia , Animais , Antibacterianos/farmacologia , Morte Celular/efeitos dos fármacos , Morte Celular/efeitos da radiação , Contagem de Colônia Microbiana , Desinfecção , Escherichia coli/efeitos dos fármacos , Escherichia coli/ultraestrutura , Glutationa/química , Testes de Sensibilidade Microbiana , Oxirredução , Ratos , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/ultraestrutura , Superóxidos/análise , Propriedades de Superfície , Temperatura , Titânio/farmacologia
5.
Small ; 14(9)2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29251423

RESUMO

Photodynamic therapy (PDT) utilizing light-induced reactive oxygen species (ROS) is a promising alternative to combat antibiotic-resistant bacteria and biofilm. However, the photosensitizer (PS)-modified surface only exhibits antibacterial properties in the presence of light. It is known that extended photoirradiation may lead to phototoxicity and tissue hypoxia, which greatly limits PDT efficiency, while ambient pathogens also have the opportunity to attach to biorelevant surfaces in medical facilities without light. Here, an antimicrobial film composed of black phosphorus nanosheets (BPSs) and poly (4-pyridonemethylstyrene) endoperoxide (PPMS-EPO) to control the storage and release of ROS reversibly is introduced. BPS, as a biocompatible PS, can produce high singlet oxygen under the irradiation of visible light of 660 nm, which can be stably stored in PPMS-EPO. The ROS can be gradually thermally released in the dark. In vitro antibacterial studies demonstrate that the PPMS-EPO/BPS film exhibits a rapid disinfection ability with antibacterial rate of 99.3% against Escherichia coli and 99.2% against Staphylococcus aureus after 10 min of irradiation. Even without light, the corresponding antibacterial rate reaches 76.5% and 69.7%, respectively. In addition, incorporating PPMS significantly improves the chemical stability of the BPS.


Assuntos
Fósforo/química , Fármacos Fotossensibilizantes/química , Espécies Reativas de Oxigênio/química , Nanoestruturas/química , Fotoquimioterapia , Polímeros/química
6.
Acta Biomater ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38876454

RESUMO

Biodegradable Zn alloys show great potential for vascular stents due to their moderate degradation rates and acceptable biocompatibility. However, the poor mechanical properties limit their applications. In this study, low alloyed Zn-2Cu-xLi (x = 0.004, 0.01, 0.07 wt %) alloys with favorable mechanical properties were developed. The microstructure consists of fine equiaxed η-Zn grains, micron, submicron-sized and coherent nano ε-CuZn4 phases. The introduced Li exists as a solute in the η-Zn matrix and ε-CuZn4 phase, and results in the increase of ε-CuZn4 volume fraction, the refinement of grains and more uniform distribution of grain sizes. As Li content increases, the strength of alloys is dramatically improved by grain boundary strengthening, precipitate strengthening of ε-CuZn4 and solid solution strengthening of Li. Zn-2Cu-0.07Li alloy has the optimal mechanical properties with a tensile yield strength of 321.8 MPa, ultimate tensile strength of 362.3 MPa and fracture elongation of 28.0 %, exceeding the benchmark of stents. It also has favorable mechanical property stability, weak tension compression yield asymmetry and strain rate sensitivity. It exhibits uniform degradation and a little improved degradation rate of 89.5 µm∙year-1, due to the improved electrochemical activity by increased ε-CuZn4 volume fraction, and generates Li2CO3 and LiOH. It shows favorable cytocompatibility without adverse influence on endothelial cell viability by trace Li+. The fabricated microtubes show favorable mechanical properties, and stents exhibit an average radial strength of 118 kPa. The present study indicates that Zn-2Cu-0.07Li alloy is a potential and promising candidate for vascular stent applications. STATEMENT OF SIGNIFICANCE: Zn alloys are promising candidates for biodegradable vascular stents. However, improving their mechanical properties is challenging. Combining the advantages of Cu and trace Li, Zn-2Cu-xLi (x < 0.1 wt %) alloys were developed for stents. As Li increases, the strength of alloys is dramatically improved by refined grains, increased volume fraction of ε-CuZn4 and solid solution of Li. Zn-2Cu-0.07Li alloy exhibits a TYS exceeding 320 MPa, UTS exceeding 360 MPa and fracture EL of nearly 30 %. It shows favorable mechanical stability, degradation behaviors and cytocompatibility. The alloy was fabricated into microtubes and stents for mechanical property tests to verify application feasibility for the first time. This indicates that Zn-2Cu-0.07Li alloy has great potential for vascular stent applications.

7.
Mater Horiz ; 11(11): 2667-2684, 2024 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-38669042

RESUMO

Microneedles for skin regeneration are conventionally restricted by uncontrollable multi-drug release, limited types of drugs, and poor wound adhesion. Here, a novel core-shell microneedle patch is developed for scarless skin repair, where the shell is composed of hydrophilic gelatin methacryloyl (GelMA) loaded with mangiferin, an anti-inflammatory small molecule, and the core is composed of hydrophobic poly (lactide-co-propylene glycol-co-lactide) dimethacrylates (PGLADMA) loaded with bioactive macromolecule and human mesenchymal stromal cell (hMSC)-derived exosomes. This material choice provides several benefits: the GelMA shell provides a swelling interface for tissue interlocking and rapid release of mangiferin at an early wound healing stage for anti-inflammation, whereas the PGLADMA core offers long-term encapsulation and release of exosomes (30% release in 3 weeks), promoting sustained angiogenesis and anti-inflammation. Our results demonstrate that the core-shell microneedle possesses anti-inflammatory properties and can induce angiogenesis both in vitro in terms of macrophage polarization and tube formation of human umbilical vein endothelial cells (HUVECs), and in vivo in terms of anti-inflammation, re-epithelization, and vessel formation. Importantly, we also observe reduced scar formation in vivo. Altogether, the degradation dynamics of our hydrophilic/hydrophobic materials enable the design of a core-shell microneedle for differential and prolonged release, promoting scarless skin regeneration, with potential for other therapies of long-term exosome release.


Assuntos
Exossomos , Células Endoteliais da Veia Umbilical Humana , Células-Tronco Mesenquimais , Agulhas , Cicatrização , Xantonas , Exossomos/metabolismo , Humanos , Xantonas/administração & dosagem , Xantonas/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Animais , Regeneração/efeitos dos fármacos , Regeneração/fisiologia , Pele/metabolismo , Pele/efeitos dos fármacos , Gelatina/química , Preparações de Ação Retardada , Camundongos , Masculino
8.
ACS Nano ; 18(23): 15114-15129, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38798240

RESUMO

Implant-related secondary infections are a challenging clinical problem. Sonodynamic therapy (SDT) strategies are promising for secondary biofilm infections by nonsurgical therapy. However, the inefficiency of SDT in existing acoustic sensitization systems limits its application. Therefore, we take inspiration from popular metamaterials and propose the design idea of a metainterface heterostructure to improve SDT efficiency. The metainterfacial heterostructure is defined as a periodic arrangement of heterointerface monoclonal cells that amplify the intrinsic properties of the heterointerface. Herein, we develop a TiO2/Ti2O3/vertical graphene metainterface heterostructure film on titanium implants. This metainterface heterostructure exhibits extraordinary sonodynamic and acoustic-to-thermal conversion effects under low-intensity ultrasound. The modulation mechanisms of the metainterface for electron accumulation and separation are revealed. The synergistic sonodynamic/mild sonothermal therapy disrupts biofilm infections (antibacterial rates: 99.99% for Staphylococcus aureus, 99.54% for Escherichia coli), and the osseointegration ability of implants is significantly improved in in vivo tests. Such a metainterface heterostructure film lays the foundation for the metainterface of manipulating electron transport to enhance the catalytic performance and holding promise for addressing secondary biofilm infections.


Assuntos
Antibacterianos , Biofilmes , Escherichia coli , Staphylococcus aureus , Titânio , Terapia por Ultrassom , Biofilmes/efeitos dos fármacos , Titânio/química , Titânio/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia , Escherichia coli/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Grafite/química , Grafite/farmacologia , Camundongos , Animais , Testes de Sensibilidade Microbiana
9.
Mater Horiz ; 11(11): 2759, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38716898

RESUMO

Correction for 'A differential-targeting core-shell microneedle patch with coordinated and prolonged release of mangiferin and MSC-derived exosomes for scarless skin regeneration' by Shang Lyu et al., Mater. Horiz., 2024, https://doi.org/10.1039/D3MH01910A.

10.
Nat Commun ; 15(1): 1030, 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38310104

RESUMO

Secretin, though originally discovered as a gut-derived hormone, is recently found to be abundantly expressed in the ventromedial hypothalamus, from which the central neural system controls satiety, energy metabolism, and bone homeostasis. However, the functional significance of secretin in the ventromedial hypothalamus remains unclear. Here we show that the loss of ventromedial hypothalamus-derived secretin leads to osteopenia in male and female mice, which is primarily induced by diminished cAMP response element-binding protein phosphorylation and upregulation in peripheral sympathetic activity. Moreover, the ventromedial hypothalamus-secretin inhibition also contributes to hyperphagia, dysregulated lipogenesis, and impaired thermogenesis, resulting in obesity in male and female mice. Conversely, overexpression of secretin in the ventromedial hypothalamus promotes bone mass accrual in mice of both sexes. Collectively, our findings identify an unappreciated secretin signaling in the central neural system for the regulation of energy and bone metabolism, which may serve as a new target for the clinical management of obesity and osteoporosis.


Assuntos
Hipotálamo , Secretina , Camundongos , Masculino , Feminino , Animais , Secretina/metabolismo , Hipotálamo/metabolismo , Obesidade/genética , Obesidade/metabolismo , Homeostase/fisiologia , Metabolismo Energético
11.
J Biomed Mater Res A ; 111(12): 1888-1902, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37555381

RESUMO

Biomaterials for nucleus pulposus (NP) replacement and regeneration have great potential to restore normal biomechanics in degenerated intervertebral discs following nucleotomy. Mechanical characterizations are essential for assessing the efficacy of biomaterial implants for clinical applications. While traditional compression tests are crucial to quantify various modulus values, relaxation behaviors and fatigue resistance, rheological measurements should also be conducted to investigate the viscoelastic properties, injectability, and overall stability upon deformation. To recapitulate the physiological in vivo environment, the use of spinal models is necessary to evaluate the risk of implant extrusion and the restoration of biomechanics under different loading conditions. When designing devices for NP replacement, injectable materials are ideal to fully fill the nucleus cavity and prevent implant migration. In addition to achieving biocompatibility and desirable mechanical characteristics, biomaterial implants should be optimized to avoid implant extrusion or re-herniation post-operatively. This review discusses the most commonly used testing protocols for assessing mechanical properties of biomaterial implants and serves as reference material for enabling researchers to characterize NP implants through a unified approach whereby newly developed biomaterials may be compared and contrasted to existing devices.


Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Núcleo Pulposo , Humanos , Materiais Biocompatíveis , Disco Intervertebral/cirurgia , Disco Intervertebral/fisiologia , Próteses e Implantes , Regeneração , Degeneração do Disco Intervertebral/cirurgia
12.
Adv Mater ; 35(9): e2208681, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36524686

RESUMO

Conferring catalytic defects in sonosensitizers is of paramount importance in reinforcing sonodynamic therapy. However, the formation of such 0D defects is governed by the Schottky defect principle. Herein, 2D catalytic planar defects are designed within Ti3 C2  sheets to address this challenge. These specific planar slip dislocations with abundant Ti3+ species (Ti3 C2 -SD(Ti3+ )) can yield surface-bound O due to the effective activation of O2 , thus resulting in a substantial amount of 1 O2  generation and the 99.72% ± 0.03% bactericidal capability subject to ultrasound (US) stimulation. It is discovered that the 2D catalytic planar defects can intervene in electron transfer through the phonon drag effect-a coupling effect between surface electrons and US-triggered phonons-that simultaneously contributes to a dramatic decrease in O2  activation energy from 1.65 to 0.06 eV. This design has achieved a qualitative leap in which the US catalytic site has transformed from 0D to 2D. Moreover, it is revealed that the electron origin, electron transfer, and visible O2  activation pathway triggered by US can be attributed to the phonon-electron coupling effect. After coating with neutrophil membrane (NM) proteins, the NM-Ti3 C2 -SD(Ti3+ ) sheets further demonstrate a 6-log10  reduction in methicillin-resistant Staphylococcus aureus burden in the infected bony tissue.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Fônons , Antibacterianos , Osso e Ossos , Catálise , Proteínas de Membrana
13.
Bioact Mater ; 27: 429-446, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37152710

RESUMO

Delayed bone defect repairs lead to severe health and socioeconomic impacts on patients. Hence, there are increasing demands for medical interventions to promote bone defect healing. Recombinant proteins such as BMP-2 have been recognized as one of the powerful osteogenic substances that promote mesenchymal stem cells (MSCs) to osteoblast differentiation and are widely applied clinically for bone defect repairs. However, recent reports show that BMP-2 treatment has been associated with clinical adverse side effects such as ectopic bone formation, osteolysis and stimulation of inflammation. Here, we have identified one new osteogenic protein, named 'HKUOT-S2' protein, from Dioscorea opposita Thunb. Using the bone defect model, we have shown that the HKUOT-S2 protein can accelerate bone defect repair by activating the mTOR signaling axis of MSCs-derived osteoblasts and increasing osteoblastic biomineralization. The HKUOT-S2 protein can also modulate the transcriptomic changes of macrophages, stem cells, and osteoblasts, thereby enhancing the crosstalk between the polarized macrophages and MSCs-osteoblast differentiation to facilitate osteogenesis. Furthermore, this protein had no toxic effects in vivo. We have also identified HKUOT-S2 peptide sequence TKSSLPGQTK as a functional osteogenic unit that can promote osteoblast differentiation in vitro. The HKUOT-S2 protein with robust osteogenic activity could be a potential alternative osteoanabolic agent for promoting osteogenesis and bone defect repairs. We believe that the HKUOT-S2 protein may potentially be applied clinically as a new class of osteogenic agent for bone defect healing.

14.
Natl Sci Rev ; 10(2): nwac221, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36817841

RESUMO

While conventional bacterial pneumonia mainly centralizes avoidance of bacterial colonization, it remains unclear how to restore the host immunity for hyperactive immunocompetent primary and immunocompromised secondary bacterial pneumonia. Here, probiotic-based nanoparticles of OASCLR were formed by coating chitosan, hyaluronic acid and ononin on living Lactobacillus rhamnosus. OASCLR nanoparticles could effectively kill various clinic common pathogens and antibacterial efficiency was >99.97%. Importantly, OASCLR could modulate lung microbiota, increasing the overall richness and diversity of microbiota by decreasing pathogens and increasing probiotic and commensal bacteria. Additionally, OASCLR could target inflammatory macrophages by the interaction of OASCLR with the macrophage binding site of CD44 and alleviate overactive immune responses for hyperactive immunocompetent pneumonia. Surprisingly, OASCLR could break the state of the macrophage's poor phagocytic ability by upregulating the expression of the extracellular matrix assembly, immune activation and fibroblast activation in immunocompromised pneumonia. The macrophage's phagocytic ability was increased from 2.61% to 12.3%. Our work provides a potential strategy for hyperactive immunocompetent primary and immunocompromised secondary bacterial pneumonia.

15.
Nat Commun ; 13(1): 2461, 2022 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-35513402

RESUMO

Owing to the existence of the outer membrane barrier, most antibacterial agents cannot penetrate Gram-negative bacteria and are ineffective. Here, we report a general method for narrow-spectrum antibacterial Garcinia nanoparticles that can only be effective to kill Gram-positive bacteria, to effectively eliminate Gram-negative bacteria by creating transient nanopores in bacterial outer membrane to induce drug entry under microwaves assistance. In vitro, under 15 min of microwaves irradiation, the antibacterial efficiency of Garcinia nanoparticles against Escherichia coli can be enhanced from 6.73% to 99.48%. In vivo, MV-assisted GNs can effectively cure mice with bacterial pneumonia. The combination of molecular dynamics simulation and experimental results reveal that the robust anti-E. coli effectiveness of Garcinia nanoparticles is attributed to the synergy of Garcinia nanoparticles and microwaves. This work presents a strategy for effectively treating both Gram-negative and Gram-positive bacteria co-infected pneumonia using herbal medicine nanoparticles with MV assistance as an exogenous antibacterial auxiliary.


Assuntos
Garcinia , Nanopartículas , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Escherichia coli , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Camundongos , Testes de Sensibilidade Microbiana , Micro-Ondas
16.
Fundam Res ; 2(3): 496-504, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-38933406

RESUMO

ß-lactamase, a kind of hydrolase in multi-drug resistant pathogens, can hydrolyze ß-lactam antibiotics and make these kinds of antibiotics invalid. Small-molecular inhibitors about the enzyme and their mechanism are widely investigated but they may result in unavoidable adverse reactions and drug-resistance. Herein, we propose a new therapeutic strategy of Chinese materioherbology, in which herbal medicine or traditional Chinese medicinal herbs can be employed as biological functional materials or refreshed/excited by means of materialogy. Natural tea nanoclusters (TNCs) were extracted from tea to inhibit ß-lactamase. Different from the mechanism of small-molecular inhibitors inhibiting enzymes by binding to the corresponding active sites, the TNCs as a cap cover the protein pocket and create a spatial barrier between the active sites and antibiotics, which was named "capping-pocket" effect. TNCs were combined with amoxicillin sodium (Amo) to treat the methicillin-resistant Staphylococcus aureus (MRSA) pneumonia in mice. This combinatorial therapy remarkably outperforms antibiotic monotherapy in reducing MRSA infections and the associated inflammation in mice. The therapeutic strategy exhibited excellent biosafety, without any side effects, even in piglets. Hence, TNCs have great clinical value in potentiating ß-lactam antibiotic activity for combatting multi-drug resistant pathogen infections and the "pocket capping" effect can guide the design of new enzyme inhibitors in near future.

17.
Nat Commun ; 13(1): 2539, 2022 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-35534483

RESUMO

Extrapulmonary complications of different organ systems have been increasingly recognized in patients with severe or chronic Coronavirus Disease 2019 (COVID-19). However, limited information on the skeletal complications of COVID-19 is known, even though inflammatory diseases of the respiratory tract have been known to perturb bone metabolism and cause pathological bone loss. In this study, we characterize the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on bone metabolism in an established golden Syrian hamster model for COVID-19. SARS-CoV-2 causes significant multifocal loss of bone trabeculae in the long bones and lumbar vertebrae of all infected hamsters. Moreover, we show that the bone loss is associated with SARS-CoV-2-induced cytokine dysregulation, as the circulating pro-inflammatory cytokines not only upregulate osteoclastic differentiation in bone tissues, but also trigger an amplified pro-inflammatory cascade in the skeletal tissues to augment their pro-osteoclastogenesis effect. Our findings suggest that pathological bone loss may be a neglected complication which warrants more extensive investigations during the long-term follow-up of COVID-19 patients. The benefits of potential prophylactic and therapeutic interventions against pathological bone loss should be further evaluated.


Assuntos
COVID-19 , Animais , COVID-19/complicações , Cricetinae , Modelos Animais de Doenças , Humanos , Mesocricetus , SARS-CoV-2
18.
Adv Sci (Weinh) ; 8(15): e2002211, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34145798

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) biofilm infections after orthopedic implant increase the risk of failure and potentially cause amputation of limbs or life-threatening sepsis in severe cases. Additionally, satisfactory bone-implant integration is another important indicator of an ideal implant. Here, an antibiotic-free antibacterial nanofilm based on oxide perovskite-type calcium titanate (CTO)/fibrous red phosphorus (RP) on titanium implant surface (Ti-CTO/RP) in which the P-N heterojunction and internal electric field are established at the heterointerface, is designed. Near-infrared light-excited electron-hole pairs are effectively separated and transferred through the synergism of the internal electric field and band offset, which strongly boosts the photocatalytic eradication of MRSA biofilms by reactive oxygen species with an efficacy of 99.42% ± 0.22% in vivo. Additionally, the charge transfer endows the heterostructure with hyperthermia to assist biofilm eradication. Furthermore, CTO/RP nanofilm provides a superior biocompatible and osteoconductive platform that enables the proliferation and osteogenic differentiation of mesenchymal stem cells, thus contributing to the subsequent implant-to-bone osseointegration after eradicating MRSA biofilms.


Assuntos
Biofilmes , Compostos de Cálcio/farmacologia , Cálcio/farmacologia , Staphylococcus aureus Resistente à Meticilina , Osseointegração/fisiologia , Óxidos/farmacologia , Fósforo/farmacologia , Fototerapia/métodos , Titânio/farmacologia , Animais , Técnicas In Vitro , Raios Infravermelhos , Modelos Animais , Próteses e Implantes , Ratos
19.
Adv Mater ; 33(5): e2006047, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33349987

RESUMO

Sonodynamic therapy (SDT) is considered to be a potential treatment for various diseases including cancers and bacterial infections due to its deep penetration ability and biosafety, but its SDT efficiency is limited by the hypoxia environment of deep tissues. This study proposes creating a potential solution, sonothermal therapy, by developing the ultrasonic interfacial engineering of metal-red phosphorus (RP), which has an obviously improved sonothermal ability of more than 20 °C elevation under 25 min of continuous ultrasound (US) excitation as compared to metal alone. The underlying mechanism is that the mechanical energy of the US activates the motion of the interfacial electrons. US-induced electron motion in the RP can efficiently transfer the US energy into phonons in the forms of heat and lattice vibrations, resulting in a stronger US absorption of metal-RP. Unlike the nonspecific heating of the cavitation effect induced by US, titanium-RP can be heated in situ when the US penetrates through 2.5 cm of pork tissue. In addition, through a sonothermal treatment in vivo, bone infection induced by multidrug-resistant Staphylococcus aureus (MRSA) is successfully eliminated in under 20 min of US without tissue damage. This work provides a new strategy for combating MRSA by strong sonothermal therapy through US interfacial engineering.


Assuntos
Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Engenharia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Fósforo/química , Terapia por Ultrassom , Espécies Reativas de Oxigênio/metabolismo
20.
Macromol Biosci ; 21(1): e2000252, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32881309

RESUMO

Bacterial infectious diseases and bacterial-infected environments have been threatening the health of human beings all over the world. In view of the increased bacteria resistance caused by overuse or improper use of antibiotics, antibacterial biomaterials are developed as the substitutes for antibiotics in some cases. Among them, antibacterial hydrogels are attracting more and more attention due to easy preparation process and diversity of structures by changing their chemical cross-linkers via covalent bonds or noncovalent physical interactions, which can endow them with various specific functions such as high toughness and stretchability, injectability, self-healing, tissue adhesiveness and rapid hemostasis, easy loading and controlled drug release, superior biocompatibility and antioxidation as well as good conductivity. In this review, the recent progress of antibacterial hydrogel including the fabrication methodologies, interior structures, performances, antibacterial mechanisms, and applications of various antibacterial hydrogels is summarized. According to the bacteria-killing modes of hydrogels, several representative hydrogels such as silver nanoparticles-based hydrogel, photoresponsive hydrogel including photothermal and photocatalytic, self-bacteria-killing hydrogel such as inherent antibacterial peptides and cationic polymers, and antibiotics-loading hydrogel are focused on. Furthermore, current challenges of antibacterial hydrogels are discussed and future perspectives in this field are also proposed.


Assuntos
Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Hidrogéis/uso terapêutico , Nanopartículas Metálicas/química , Antibacterianos/química , Antioxidantes/química , Antioxidantes/uso terapêutico , Infecções Bacterianas/microbiologia , Materiais Biocompatíveis/química , Materiais Biocompatíveis/uso terapêutico , Preparações de Ação Retardada/uso terapêutico , Humanos , Hidrogéis/química , Prata/química , Cicatrização/efeitos dos fármacos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA