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1.
Adv Mater ; : e2406192, 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-39003609

RESUMEN

Bioelectricity provides electrostimulation to regulate cell/tissue behaviors and functions. In the human body, bioelectricity can be generated in electromechanically responsive tissues and organs, as well as biomolecular building blocks that exhibit piezoelectricity, with a phenomenon known as the piezoelectric effect. Inspired by natural bio-piezoelectric phenomenon, efforts have been devoted to exploiting high-performance synthetic piezoelectric biomaterials, including molecular materials, polymeric materials, ceramic materials, and composite materials. Notably, piezoelectric biomaterials polarize under mechanical strain and generate electrical potentials, which can be used to fabricate electronic devices. Herein, a review article is proposed to summarize the design and research progress of piezoelectric biomaterials and devices toward bionanotechnology. First, the functions of bioelectricity in regulating human electrophysiological activity from cellular to tissue level are introduced. Next, recent advances as well as structure-property relationship of various natural and synthetic piezoelectric biomaterials are provided in detail. In the following part, the applications of piezoelectric biomaterials in tissue engineering, drug delivery, biosensing, energy harvesting, and catalysis are systematically classified and discussed. Finally, the challenges and future prospects of piezoelectric biomaterials are presented. It is believed that this review will provide inspiration for the design and development of innovative piezoelectric biomaterials in the fields of biomedicine and nanotechnology.

2.
J Mater Chem B ; 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39045831

RESUMEN

Biomineralization is a natural process in which organisms regulate the growth of inorganic minerals to form biominerals with unique layered structures, such as bones and teeth, primarily composed of calcium and phosphorus. Tooth decay significantly impacts our daily lives, and the key to tooth regeneration lies in restoring teeth through biomimetic approaches, utilizing mineralization strategies or materials that mimic natural processes. This review delves into the types, properties, and transformations of calcium and phosphorus minerals, followed by an exploration of the mechanisms behind physiological and pathological mineralization in living organisms. It summarizes the mechanisms and commonalities of biomineralization and discusses the advancements in dental biomineralization research, guided by insights into calcium and phosphorus mineral biomineralization. This review concludes by addressing the current challenges and future directions in the field of dental biomimetic mineralization.

3.
ACS Nano ; 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39083438

RESUMEN

Cancer stem cells (CSCs) are promising targets for improving anticancer treatment outcomes while eliminating recurrence, but their treatment remains a major challenge. Here, we report a nanointegrative strategy to realize CSC-targeted ferroptosis-immunotherapy through spatiotemporally controlled reprogramming of STAT3-regulated signaling circuits. Specifically, STAT3 inhibitor niclosamide (Ni) and an experimental ferroptosis drug (1S, 3R)-RSL3 (RSL3) are integrated into hyaluronic acid-modified amorphous calcium phosphate (ACP) nanounits through biomineralization (CaP-PEG-HA@Ni/RSL3), which could be recognized by CD44-overexpressing CSCs and released in a synchronized manner. Ni inhibits the CSC-intrinsic STAT3-PD-L1 axis to stimulate adaptive immunity and enhance interferon gamma (IFNγ) secretion by CD8+ T cells to downregulate SLC7A11 and SLC3A2 for blocking glutathione biosynthesis. Meanwhile, Ni-dependent STAT3 inhibition also upregulates ACSL4 through downstream signaling and IFNγ feedback. These effects cooperate with RSL3-mediated GPX4 deactivation to induce pronounced ferroptosis. Furthermore, CaP-PEG-HA@Ni/RSL3 also impairs the immunosuppressive M2-like tumor-associated macrophages, while Ca2+ ions released from degraded ACP could chelate with lipid peroxides in ferroptotic CSCs to avoid CD8+ T-cell inhibition, thus boosting the effector function of activated CD8+ T cells. This study offers a cooperative ferroptosis-immunotherapeutic approach for the treatment of refractory cancer.

4.
Biomaterials ; 311: 122649, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38850718

RESUMEN

Innovative solutions are required for the intervention of implant associated infections (IAIs), especially for bone defect patients with chronic inflammatory diseases like diabetes mellitus (DM). The complex immune microenvironment of infections renders implants with direct antibacterial ability inadequate for the prolonged against of bacterial infections. Herein, a synergistic treatment strategy was presented that combined sonodynamic therapy (SDT) with adaptive immune modulation to treat IAIs in diabetes patients. A multifunctional coating was created on the surface of titanium (Ti) implants, consisting of manganese dioxide nanoflakes (MnO2 NFs) with cascade catalytic enzyme activity and a responsive degradable hydrogel containing a sonosensitizer. The reactive oxygen species (ROS) generated by glucose-hydrogen peroxide (H2O2) cascade catalysis and ultrasound (US) activation sonosensitizer helped kill bacteria and release bacterial antigens. Meanwhile, Mn2+ facilitated dendritic cells (DCs) maturation, enhancing antigen presentation to activate both cellular and humoral adaptive immunity against bacterial infections. This approach effectively eliminated bacteria in established diabetic IAIs model and activated systemic antibacterial immunity, providing long-term antibacterial protection. This study presents a non-antibiotic immunotherapeutic strategy for fighting IAIs in chronic diseases.

5.
ACS Nano ; 18(27): 17651-17671, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38932673

RESUMEN

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.


Asunto(s)
Hidrogeles , Hidrogeles/química , Hidrogeles/farmacología , Animales , Ratas , Adherencias Tisulares/prevención & control , Ratas Sprague-Dawley , Antibacterianos/farmacología , Antibacterianos/química , Masculino , Antiinflamatorios/química , Antiinflamatorios/farmacología
6.
Biosens Bioelectron ; 260: 116435, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-38820724

RESUMEN

Electrochemical detection of miRNA biomarkers in complex physiological samples holds great promise for accurate evaluation of tumor burden in the perioperative period, yet limited by reproducibility and bias issues. Here, nanosensors installed with hybrid probes that responsively release catalytic DNAzymes (G-quadruplexes/hemin) were developed to solve the fidelity challenge in an immobilization-free detection. miRNA targets triggered toehold-mediated strand displacement reactions on the sensor surface and resulted in amplified shedding of DNAzymes. Subsequently, the interference background was removed by Fe3O4 core-facilitated magnetic separation. Binding aptamers of the electrochemical reporter (dopamine) were tethered closely to the catalytic units for boosting H2O2-mediated oxidation through proximity catalysis. The one-to-many conversion by dual amplification from biological-chemical catalysis facilitated sufficient homogeneous sensing signals on electrodes. Thereby, the nanosensor exhibited a low detection limit (2.08 fM), and high reproducibility (relative standard deviation of 1.99%). Most importantly, smaller variations (RSD of 0.51-1.04%) of quantified miRNAs were observed for detection from cell lysates, multiplexed detection from unprocessed serum, and successful discrimination of small upregulations in lysates of tumor tissue samples. The nanosensor showed superior diagnostic performance with an area under curve (AUC) of 0.97 and 94% accuracy in classifying breast cancer patients and healthy donors. These findings demonstrated the synergy of signal amplification and interference removal in achieving high-fidelity miRNA detection for practical clinical applications.


Asunto(s)
Técnicas Biosensibles , ADN Catalítico , Técnicas Electroquímicas , Límite de Detección , MicroARNs , Humanos , MicroARNs/aislamiento & purificación , Técnicas Electroquímicas/métodos , ADN Catalítico/química , Catálisis , G-Cuádruplex , Neoplasias de la Mama , Peróxido de Hidrógeno/química , Aptámeros de Nucleótidos/química , Femenino , Hemina/química , Reproducibilidad de los Resultados , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética
7.
J Mater Chem B ; 12(23): 5722-5733, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38764419

RESUMEN

Hepatic ischemia-reperfusion injury (IRI) is a common pathological process during hepatectomy and liver transplantation and the two primary reasons for hepatic IRI are reactive oxygen species (ROS)-mediated oxidative stress and excessive inflammatory responses. Herein, a novel antioxidant nanodrug (A-MPDA@Fe3O4@PVP) is prepared by employing L-arginine-doped mesoporous polydopamine (A-MPDA) nanoparticles as the carrier for deposition of ultra-small ferric oxide (Fe3O4) nanoparticles and further surface modification with polyvinylpyrrolidone (PVP). A-MPDA@Fe3O4@PVP not only effectively reduces the aggregation of ultra-small Fe3O4, but also simultaneously replicates the catalytic activity of catalase (CAT) and superoxide dismutase (SOD). A-MPDA@Fe3O4@PVP with good antioxidant activity can rapidly remove various toxic reactive oxygen species (ROS) and effectively regulate macrophage polarization in vitro. In the treatment of hepatic IRI, A-MPDA@Fe3O4@PVP effectively alleviates ROS-induced oxidative stress, reduces the expression of inflammatory factors, and prevents apoptosis of hepatocytes through immune regulation. A-MPDA@Fe3O4@PVP can further protect liver tissue by activating the PPARγ/NF-κB pathway. This multiplex antioxidant enzyme therapy can provide new references for the treatment of IRI in organ transplantation and other ROS-related injuries such as fibrosis, cirrhosis, and bacterial and hepatic viral infection.


Asunto(s)
FN-kappa B , PPAR gamma , Especies Reactivas de Oxígeno , Daño por Reperfusión , Especies Reactivas de Oxígeno/metabolismo , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Animales , FN-kappa B/metabolismo , PPAR gamma/metabolismo , Ratones , Hígado/efectos de los fármacos , Hígado/patología , Hígado/metabolismo , Polímeros/química , Polímeros/farmacología , Povidona/química , Povidona/farmacología , Indoles/química , Indoles/farmacología , Masculino , Antioxidantes/farmacología , Antioxidantes/química , Estrés Oxidativo/efectos de los fármacos , Células RAW 264.7 , Nanopartículas de Magnetita/química , Humanos
8.
Adv Healthc Mater ; 13(17): e2303814, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38497832

RESUMEN

In this study, the regulatory role and mechanisms of tantalum (Ta) particles in the bone tissue microenvironment are explored. Ta particle deposition occurs in both clinical samples and animal tissues following porous Ta implantation. Unlike titanium (Ti) particles promoting M1 macrophage (Mϕ) polarization, Ta particles regulating calcium signaling pathways and promoting M2 Mϕ polarization. Ta-induced M2 Mϕ enhances bone marrow-derived mesenchymal stem cells (BMSCs) proliferation, migration, and osteogenic differentiation through exosomes (Exo) by upregulating miR-378a-3p/miR-221-5p and downregulating miR-155-5p/miR-212-5p. Ta particles suppress the pro-inflammatory and bone resorption effects of Ti particles in vivo and in vitro. In a rat femoral condyle bone defect model, artificial bone loaded with Ta particles promotes endogenous Mϕ polarization toward M2 differentiation at the defect site, accelerating bone repair. In conclusion, Ta particles modulate Mϕ polarization toward M2 and influence BMSCs osteogenic capacity through Exo secreted by M2 Mϕ, providing insights for potential bone repair applications.


Asunto(s)
Diferenciación Celular , Exosomas , Macrófagos , Células Madre Mesenquimatosas , MicroARNs , Osteogénesis , Tantalio , Animales , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/citología , Exosomas/metabolismo , Tantalio/química , Tantalio/farmacología , Osteogénesis/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/citología , Ratas , Diferenciación Celular/efectos de los fármacos , MicroARNs/metabolismo , Ratas Sprague-Dawley , Humanos , Masculino , Proliferación Celular/efectos de los fármacos , Huesos/metabolismo
9.
Biomaterials ; 308: 122548, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38554642

RESUMEN

The treatment of infected wounds poses a formidable challenge in clinical practice due to the detrimental effects of uncontrolled bacterial infection and excessive oxidative stress, resulting in prolonged inflammation and impaired wound healing. In this study, we presented a MXene@TiO2 (MT) nanosheets loaded composite hydrogel named as GA/OKGM/MT hydrogel, which was formed based on the Schiff base reaction between adipic dihydrazide modified gelatin (GA)and Oxidized Konjac Glucomannan (OKGM), as the wound dressing. During the hemostasis phase, the GA/OKGM/MT hydrogel demonstrated effective adherence to the skin, facilitating rapid hemostasis. In the subsequent inflammation phase, the GA/OKGM/MT hydrogel effectively eradicated bacteria through MXene@TiO2-induced photothermal therapy (PTT) and eliminated excessive reactive oxygen species (ROS), thereby facilitating the transition from the inflammation phase to the proliferation phase. During the proliferation phase, the combined application of GA/OKGM/MT hydrogel with electrical stimulation (ES) promoted fibroblast proliferation and migration, leading to accelerated collagen deposition and angiogenesis at the wound site. Overall, the comprehensive repair strategy based on the GA/OKGM/MT hydrogel demonstrated both safety and reliability. It expedited the progression through the hemostasis, inflammation, and proliferation phases of wound healing, showcasing significant potential for the treatment of infected wounds.


Asunto(s)
Proliferación Celular , Gelatina , Hemostasis , Hidrogeles , Mananos , Titanio , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Titanio/química , Hidrogeles/química , Animales , Proliferación Celular/efectos de los fármacos , Ratones , Hemostasis/efectos de los fármacos , Gelatina/química , Mananos/química , Masculino , Terapia Fototérmica , Nanoestructuras/química , Especies Reactivas de Oxígeno/metabolismo , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/terapia , Humanos
10.
Pharmacol Res ; 202: 107121, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38431091

RESUMEN

Bone homeostasis is maintained by osteoclast-mediated bone resorption and osteoblast-mediated bone formation. A dramatic decrease in estrogen levels in postmenopausal women leads to osteoclast overactivation, impaired bone homeostasis, and subsequent bone loss. Changes in the gut microbiome affect bone mineral density. However, the role of the gut microbiome in estrogen deficiency-induced bone loss and its underlying mechanism remain unknown. In this study, we found that the abundance of Clostridium sporogenes (C. spor.) and its derived metabolite, indole propionic acid (IPA), were decreased in ovariectomized (OVX) mice. In vitro assays suggested that IPA suppressed osteoclast differentiation and function. At the molecular level, IPA suppressed receptor activator of nuclear factor kappa-Β ligand (RANKL)-induced pregnane X receptor (PXR) ubiquitination and degradation, leading to increased binding of remaining PXR with P65. In vivo daily IPA administration or repeated C. spor. colonization protected against OVX-induced bone loss. To protect live bacteria from the harsh gastric environment and delay the emptying of orally administered C. spor. from the intestine, a C. spor.-encapsulated silk fibroin (SF) hydrogel system was developed, which achieved bone protection in OVX mice comparable to that achieved with repeated germ transplantation or daily IPA administration. Overall, we found that gut C. spor.-derived IPA was involved in estrogen deficiency-induced osteoclast overactivation by regulating the PXR/P65 complex. The C. spor.-encapsulated SF hydrogel system is a promising tool for combating postmenopausal osteoporosis without the disadvantages of repeated germ transplantation.


Asunto(s)
Resorción Ósea , Clostridium , Osteoclastos , Propionatos , Humanos , Femenino , Ratones , Animales , Osteoclastos/metabolismo , Receptor X de Pregnano/metabolismo , Resorción Ósea/metabolismo , Osteogénesis , Estrógenos/metabolismo , Indoles/metabolismo , Hidrogeles , Ligando RANK/metabolismo , Diferenciación Celular
11.
J Biomed Mater Res A ; 112(9): 1412-1423, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38461494

RESUMEN

Dental enamel is a mineralized extracellular matrix, and enamel defect is a common oral disease. However, the self-repair capacity of enamel is limited due to the absence of cellular components and organic matter. Efficacy of biomimetic enamel mineralization using calcium phosphate ion clusters (CPICs), is an effective method to compensate for the limited self-healing ability of fully developed enamel. Preparing and stabilizing CPICs presents a significant challenge, as the addition of certain stabilizers can diminish the mechanical properties or biosafety of mineralized enamel. To efficiently and safely repair enamel damage, this study quickly prepared CPICs without stabilizers using the atomization method. The formed CPICs were evenly distributed on the enamel surface, prompting directional growth and transformation of hydroxyapatite (HA) crystals. The study revealed that the mended enamel displayed comparable morphology, chemical composition, hardness, and mechanical properties to those of the original enamel. The approach of repairing dental enamel by utilizing ultrasonic nebulization of CPICs is highly efficient and safe, therefore indicating great promise.


Asunto(s)
Materiales Biomiméticos , Fosfatos de Calcio , Esmalte Dental , Fosfatos de Calcio/química , Esmalte Dental/química , Materiales Biomiméticos/química , Humanos , Biomimética/métodos , Durapatita/química , Animales
12.
ACS Nano ; 18(11): 8360-8382, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38457334

RESUMEN

Supramolecular hydrogels emerge as a promising paradigm for sutureless wound management. However, their translation is still challenged by the insufficient mechanical robustness in the context of complex wounds in dynamic tissues. Herein, we report a tissue-adhesive supramolecular hydrogel membrane based on biocompatible precursors for dressing wounds in highly dynamic tissues, featuring robust mechanical resilience through programmable strain-adaptive entanglement among microdomains. Specifically, the hydrogels are synthesized by incorporating a long-chain polyurethane segment into a Schiff base-ligated short-chain oxidized cellulose/quaternized chitosan network via acylhydrazone bonding, which readily establishes interpenetrating entangled microdomains in dynamic cross-linked hydrogel matrices to enhance their tear and fatigue resistance against extreme mechanical stresses. After being placed onto dynamic tissues, the hydrogel dressing could efficiently absorb blood to achieve rapid hemostasis. Moreover, metal ions released from ruptured erythrocytes could be scavenged by the Schiff base linkers to form additional ionic bonds, which would trigger the cross-linking of the short-chain components and establish abundant crystalline microdomains, eventually leading to the in situ stiffening of the hydrogels to endure heavy mechanical loads. Benefiting from its hemostatic capacity and strain adaptable mechanical performance, this hydrogel wound dressing shows promise for the clinical management of various traumatic wounds.


Asunto(s)
Quitosano , Hemostáticos , Hidrogeles , Bases de Schiff , Hemostasis , Antibacterianos
13.
Bioact Mater ; 36: 287-300, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38496033

RESUMEN

The rheumatoid arthritis (RA) microenvironment is often followed by a vicious circle of high inflammation, endogenous gas levels imbalance, and poor treatment. To break the circle, we develop a dual-gas-mediated injectable hydrogel for modulating the immune microenvironment of RA and simultaneously releasing therapeutic drugs. The hydrogel (DNRS gel) could be broken down on-demand by consuming excessive nitric oxide (NO) and releasing therapeutic hydrogen sulfide (H2S), resulting in endogenous gas restoration, inflammation alleviation, and macrophage polarization to M2 type. Additionally, the hydrogel could suppress osteoclastogenesis and enhance osteogenesis. Furthermore, the intra-articularly injected hydrogel with methotrexate (MTX/DNRS gel) significantly alleviated inflammation and clinical symptoms and promoted the repair of bone erosion in the collagen-induced arthritis rat model. As a result, in vivo results demonstrated that MTX/DNRS gel restored the microenvironment and improved the therapeutic effect of MTX. This study provides a novel understanding of developing versatile smart delivery platforms for RA treatment.

14.
ACS Nano ; 18(14): 9871-9885, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38545939

RESUMEN

As an ideal drug carrier, it should possess high drug loading and encapsulation efficiency and precise drug targeting release. Herein, we utilized a template-guided self-weaving technology of phase-separated silk fibroin (SF) in reverse microemulsion (RME) to fabricate a kind of hyaluronic acid (HA) coated SF nanocage (HA-gNCs) for drug delivery of cancer immunotherapy. Due to the hollow structure, HA-gNCs were capable of simultaneous encapsulation of the anti-inflammatory drug betamethasone phosphate (BetP) and the immune checkpoint blockade (ICB) agent PD-L1 antibody (αPD-L1) efficiently. Another point worth noting was that the thiocarbonate cross-linkers used to strengthen the SF shell of HA-gNCs could be quickly broken by overexpressed glutathione (GSH) to reach responsive drug release inside tumor tissues accompanied by hydrogen sulfide (H2S) production in one step. The synergistic effect of released BetP and generated H2S guaranteed chronological modulation of the immunosuppressive tumor microenvironment (ITME) to amplify the therapeutic effect of αPD-L1 for the growth, metastasis, and recurrence of tumors. This study highlighted the exceptional prospect of HA-gNCs as a self-assistance platform for cancer drug delivery.


Asunto(s)
Antineoplásicos , Sulfuro de Hidrógeno , Nanopartículas , Neoplasias , Humanos , Sulfuro de Hidrógeno/uso terapéutico , Antineoplásicos/uso terapéutico , Sistemas de Liberación de Medicamentos/métodos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Glutatión , Inmunoterapia , Microambiente Tumoral , Línea Celular Tumoral , Nanopartículas/química
15.
Small ; 20(25): e2307247, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38243871

RESUMEN

Oral treatment of colon diseases with the CRISPR/Cas9 system has been hampered by the lack of a safe and efficient delivery platform. Overexpressed CD98 plays a crucial role in the progression of ulcerative colitis (UC) and colitis-associated colorectal cancer (CAC). In this study, lipid nanoparticles (LNPs) derived from mulberry leaves are functionalized with Pluronic copolymers and optimized to deliver the CRISPR/Cas gene editing machinery for CD98 knockdown. The obtained LNPs possessed a hydrodynamic diameter of 267.2 nm, a narrow size distribution, and a negative surface charge (-25.6 mV). Incorporating Pluronic F127 into LNPs improved their stability in the gastrointestinal tract and facilitated their penetration through the colonic mucus barrier. The galactose end groups promoted endocytosis of the LNPs by macrophages via asialoglycoprotein receptor-mediated endocytosis, with a transfection efficiency of 2.2-fold higher than Lipofectamine 6000. The LNPs significantly decreased CD98 expression, down-regulated pro-inflammatory cytokines (TNF-α and IL-6), up-regulated anti-inflammatory factors (IL-10), and polarized macrophages to M2 phenotype. Oral administration of LNPs mitigated UC and CAC by alleviating inflammation, restoring the colonic barrier, and modulating intestinal microbiota. As the first oral CRISPR/Cas9 delivery LNP, this system offers a precise and efficient platform for the oral treatment of colon diseases.


Asunto(s)
Sistemas CRISPR-Cas , Lípidos , Morus , Nanopartículas , Hojas de la Planta , Nanopartículas/química , Hojas de la Planta/química , Animales , Administración Oral , Morus/química , Lípidos/química , Ratones , Enfermedades del Colon/terapia , Humanos , Masculino , Liposomas
16.
Mater Today Bio ; 24: 100912, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38226010

RESUMEN

Angiogenesis at the fracture site plays crucial roles in the endogenous osteogenesis process and is a prerequisite for the efficient repair of implant fixed bone defects. To improve the peri-implant vascularization of titanium implant for accelerating defect healing, we developed a Co-doped Mg-Al layered hydroxide coating on the surface of titanium using hydrothermal reaction and then modified the surface with gallic acid (Ti-LDH/GA). Gallic acid coating enabled the sustained release of Co2+ and Mg2+ to the defect site over a month. Ti-LDH/GA treatment profoundly stimulated the angiogenic potential of endothelial cells by upregulating the vascularization regulators such as vascular endothelial growth factor VEGF) and hypoxia-inducible factor-1α (HIF-1α), leading to enhanced osteogenic capability of mesenchymal stem cells (MSCs). These pro-bone healing benefits were attributed to the synergistic effects of Co ions and Mg ions in promoting angiogenesis and new bone formation. These insights collectively suggested the potent pro-osteogenic effect of Ti-LDH/GA through leveraging peri-implant vascularization, offering a new approach for developing biofunctional titanium implants.

17.
Colloids Surf B Biointerfaces ; 234: 113737, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38176336

RESUMEN

Titanium (Ti) and titanium alloy are the most common metal materials in clinical orthopedic surgery. However, in the initial stage of surgery and implantation, the production of excessive reactive oxygen species (ROS) can induce oxidative stress (OS) microenvironment. OS will further inhibit the growth of new bone, resulting in surgical failure. In this study, based on the fact that nanoscale manganese dioxide (MnO2) can show H2O2-like enzyme activity, a MnO2 nanocoating was prepared on mciro-nano structured surface of Ti substrate via a two-step method of alkaline thermal and hydrothermal treatment. The results of scanning electron microscopy (SEM), X-ray diffractometer (XRD) and X-ray photoelectron spectroscopy (XPS) showed that the nano-MnO2 coating was successfully fabricated on the surface of Ti substrate. The results of measurement of H2O2, dissolved O2 and intracellular ROS in vitro showed that the treated Ti substrate could efficiently eliminate H2O2 and reduce ROS. Furthermore, the modified Ti substrate could promote the early adhesion, proliferation and osteogenic differentiation of MSCs, which was demonstrated by experimental results of cell morphology, cell viability, alkaline phosphatase, collagen, and mineralization deposition. The results of quantitative real-time polymerase chain reaction (qRT-PCR) of MSCs adhered the modified Ti substrate showed that the expression of genes related to osteogenic differentiation significantly increased. More importantly, the modified Ti implant could eliminate ROS at the injury site, reduce OS and promote the regeneration of bone tissue, which was demonstrated via hematoxylin/eosin, Masson's trichrome and immunohistochemical staining. In conclusion, the modified Ti implant presented here had the effect of reducing OS and promoting osseointegration. Relevant research ideas and results provide new methods for the research and development of functional implants, which have potential application value in the field of orthopedics.


Asunto(s)
Osteogénesis , Titanio , Titanio/farmacología , Titanio/química , Compuestos de Manganeso/farmacología , Especies Reactivas de Oxígeno/metabolismo , Óxidos/farmacología , Peróxido de Hidrógeno/farmacología , Oseointegración , Propiedades de Superficie
18.
Acta Biomater ; 173: 420-431, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37979634

RESUMEN

Wound infections caused by drug-resistant bacteria pose a great threat to human health, and the development of non-drug-resistant antibacterial approaches has become a research priority. In this study, we developed Cu2O-SnO2 doped polydopamine (CSPDA) triple cubic antibacterial nanoenzymes with high photothermal conversion efficiency and good Fenton-like catalase performance. CSPDA antibacterial nanoplatform can catalyze the generation of hydroxyl radical (·OH) from H2O2 at low concentration (50 µg∙mL-1) under 808 nm near-infrared (NIR) irradiation to achieve a combined photothermal therapy (PTT) and chemodynamic therapy (CDT). And the CSPDA antibacterial nanoplatform displays broad-spectrum and long-lasting antibacterial effects against both Gram-negative Escherichia coli (100 %) and Gram-positive Staphylococcus aureus (100 %) in vitro. Moreover, in a mouse wound model with mixed bacterial infection, the nanoplatform demonstrates a significant in vivo bactericidal effect while remaining good cytocompatible. To conclude, this study successfully develops an efficient and long-lasting bacterial infection treatment system. This system provided different options for future studies on the design of synergistic antimicrobial therapy. Hence, the as-synthesized synergetic photothermal therapy and chemodynamic therapy nanoenzymes have rapid and long-term bactericidal ability, well-conglutinant performance and effectively preventing wound infection for clinical application. STATEMENT OF SIGNIFICANCE: Wound infections caused by drug-resistant bacteria pose a great threat to human health, and the development of non-drug-resistant antibacterial approaches has become a research priority. In this study, we developed Cu2O-SnO2 doped polydopamine (CSPDA) triple cubic yolk-like antibacterial nanoenzymes with high photothermal conversion efficiency and Fenton-like catalase effect for photothermal and Chemodynamic antibacterial therapy, Meanwhile, the nanocomposites exhibit good antibioadhesion in a natural water environment for a long-time immersion. In conclusion, this study successfully develops an efficient and long-lasting bacterial infection treatment system. These findings present a pioneering strategy for future research on the design of synergistic antibacterial and antibioadhesive systems.


Asunto(s)
Infecciones Bacterianas , Infección de Heridas , Humanos , Animales , Ratones , Catalasa , Peróxido de Hidrógeno/farmacología , Antibacterianos/farmacología , Modelos Animales de Enfermedad
19.
ACS Nano ; 18(2): 1257-1288, 2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38157317

RESUMEN

Inspired by natural hierarchical self-assembly of proteins and peptides, amino acids, as the basic building units, have been shown to self-assemble to form highly ordered structures through supramolecular interactions. The fabrication of functional biomaterials comprised of extremely simple biomolecules has gained increasing interest due to the advantages of biocompatibility, easy functionalization, and structural modularity. In particular, amino acid based assemblies have shown attractive physical characteristics for various bionanotechnology applications. Herein, we propose a review paper to summarize the design strategies as well as research advances of amino acid based supramolecular assemblies as smart functional materials. We first briefly introduce bioinspired reductionist design strategies and assembly mechanism for amino acid based molecular assembly materials through noncovalent interactions in condensed states, including self-assembly, metal ion mediated coordination assembly, and coassembly. In the following part, we provide an overview of the properties and functions of amino acid based materials toward applications in nanotechnology and biomedicine. Finally, we give an overview of the remaining challenges and future perspectives on the fabrication of amino acid based supramolecular biomaterials with desired properties. We believe that this review will promote the prosperous development of innovative bioinspired functional materials formed by minimalistic building blocks.


Asunto(s)
Aminoácidos , Materiales Biomiméticos , Materiales Biomiméticos/química , Nanotecnología , Péptidos/química , Materiales Biocompatibles
20.
J Mater Chem B ; 12(1): 264-274, 2023 12 22.
Artículo en Inglés | MEDLINE | ID: mdl-38088036

RESUMEN

The physicochemical environment at the sites of chronic diabetic wounds is an ideal habitat for bacteria, which exacerbate the deterioration of the microenvironment at the wound sites and consequently delay wound healing. In recent years, photothermal therapy has been considered an ideal non-antibiotic antimicrobial strategy. However, photothermal therapy alone is prone to cause damage to the body tissues. Herein, a (zeolitic imidazolate framework-8) ZIF-8/(mesoporous polydopamine) MPDA@(deoxyribonuclease I) DNase I ternary nanocomposite system was constructed, which exhibited good antimicrobial and antioxidant properties. Specifically, DNase I was first encapsulated into MPDA nanoparticles (NPs) and then coated with ZIF-8, which rapidly degrades in an acidic bacterial environment, triggering the release of antimicrobial Zn2+ and DNase I, thus enabling low-temperature (∼45 °C) PTT antimicrobial therapy. Meanwhile, the NPs can effectively regulate the oxidative stress environment at the trauma site because of the antioxidant effect of MPDA. Moreover, the experimental results of the diabetic wound infection mouse model showed that the prepared NPs could kill bacteria well and accelerate wound healing. Overall, the phototherapy strategy proposed in this study shows great potential in the treatment of chronically infected wounds.


Asunto(s)
Antiinfecciosos , Diabetes Mellitus , Infección de Heridas , Animales , Ratones , Temperatura , Fototerapia , Antioxidantes , Infección de Heridas/tratamiento farmacológico , Desoxirribonucleasa I
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