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1.
Proc Natl Acad Sci U S A ; 121(18): e2400200121, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38662550

RESUMO

Traditional metallic glasses (MGs), based on one or two principal elements, are notoriously known for their lack of tensile ductility at room temperature. Here, we developed a multiprincipal element MG (MPEMG), which exhibits a gigapascal yield strength, significant strain hardening that almost doubles its yield strength, and 2% uniform tensile ductility at room temperature. These remarkable properties stem from the heterogeneous amorphous structure of our MPEMG, which is composed of atoms with significant size mismatch but similar atomic fractions. In sharp contrast to traditional MGs, shear banding in our glass triggers local elemental segregation and subsequent ordering, which transforms shear softening to hardening, hence resulting in shear-band self-halting and extensive plastic flows. Our findings reveal a promising pathway to design stronger, more ductile glasses that can be applied in a wide range of technological fields.

2.
Soft Matter ; 20(7): 1565-1572, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38270340

RESUMO

It is natural to expect that small particles in binary mixtures move faster than large ones. However, in binary glass-forming liquids with soft-core particle interactions, we observe the counterintuitive dynamic reversal between large and small particles along with the increase of pressure by performing molecular dynamics simulations. The structural relaxation (dynamic heterogeneity) of small particles is faster (weaker) than large ones at low pressures, but becomes slower (stronger) above a crossover pressure. In contrast, this dynamic reversal never happens in glass-forming liquids with hard-core interactions. We find that the difference of the effective melting temperatures felt by large and small particles can be used to understand the dynamic reversal. In binary mixtures, we derive effective melting temperatures of large and small particles simply from the conversion of units and find that particles with a higher effective melting temperature usually undergo a slower and more heterogeneous relaxation. The presence (absence) of the dynamic reversal in soft-core (hard-core) systems is simply due to the non-monotonic (monotonic) behavior of the melting temperature as a function of pressure. Interestingly, by manipulating the relative softness between large and small particles, we obtain a special case of soft-core systems, in which large particles always have higher effective melting temperatures than small ones. As a result, the dynamic reversal is totally eliminated. Our work provides another piece of evidence of the underlying connections between the properties of non-equilibrium glass-formers and equilibrium crystal-formers.

3.
J Nanobiotechnology ; 22(1): 8, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38167113

RESUMO

Electroconductive hydrogels offer a promising avenue for enhancing the repair efficacy of spinal cord injuries (SCI) by restoring disrupted electrical signals along the spinal cord's conduction pathway. Nonetheless, the application of hydrogels composed of diverse electroconductive materials has demonstrated limited capacity to mitigate the post-SCI inflammatory response. Recent research has indicated that the transplantation of M2 microglia effectively fosters SCI recovery by attenuating the excessive inflammatory response. Exosomes (Exos), small vesicles discharged by cells carrying similar biological functions to their originating cells, present a compelling alternative to cellular transplantation. This investigation endeavors to exploit M2 microglia-derived exosomes (M2-Exos) successfully isolated and reversibly bonded to electroconductive hydrogels through hydrogen bonding for synergistic promotion of SCI repair to synergistically enhance SCI repair. In vitro experiments substantiated the significant capacity of M2-Exos-laden electroconductive hydrogels to stimulate the growth of neural stem cells and axons in the dorsal root ganglion and modulate microglial M2 polarization. Furthermore, M2-Exos demonstrated a remarkable ability to mitigate the initial inflammatory reaction within the injury site. When combined with the electroconductive hydrogel, M2-Exos worked synergistically to expedite neuronal and axonal regeneration, substantially enhancing the functional recovery of rats afflicted with SCI. These findings underscore the potential of M2-Exos as a valuable reparative factor, amplifying the efficacy of electroconductive hydrogels in their capacity to foster SCI rehabilitation.


Assuntos
Exossomos , Traumatismos da Medula Espinal , Ratos , Animais , Microglia/metabolismo , Exossomos/metabolismo , Hidrogéis/farmacologia , Traumatismos da Medula Espinal/metabolismo , Neurônios/metabolismo
4.
Phys Chem Chem Phys ; 26(6): 4968-4974, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38230694

RESUMO

Based on the excellent piezoelectric properties of 0.7Pb(Mg1/3Nb2/3)O3-0.3PbTiO3 (PMN-PT) single crystals, a hole-doped manganite film/PMN-PT heterostructure has been constructed to achieve electric-field and light co-control of physical properties. Here, we report the resistivity switching behavior of Eu0.7Sr0.3MnO3/PMN-PT(111) multiferroic heterostructures under different in-plane reading currents, temperatures, light stimuli and electric fields, and discuss the underlying coupling mechanisms of resistivity change. The transition from the electric-field induced lattice strain effect to polarization current effect can be controlled effectively by decreasing the in-plane reading current at room temperature. With the decrease of temperature, the interfacial charge effect dominates over the lattice strain effect due to the reduced charge carrier density. In addition, light stimulus can lead to the delocalization of eg carriers, and thus enhance the lattice strain effect and suppress the interfacial charge effect. This work helps to understand essential physics of magnetoelectric coupling and also provides a potential method to realize energy-efficient multi-field control of manganite thin films.

5.
J Phys Chem A ; 128(5): 829-839, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38266177

RESUMO

Global-minimum optimizations combined with relativistic quantum chemistry calculations have been performed to characterize the ground-state stable structures of four titled compounds and to analyze the bonding properties. Th2C8 was identified as being a ThC4-Th(C2)2 structure, U2C8 has been found to favor the U-U(C8) structure, and both Th3C8 and U3C8 adopt the (AnC3)2-(AnC2) structure. Then, the wave function analyses reveal that the interactions between the Th 7s-based orbital and the σg molecular orbital of the C2 unit compensate for the excitation energy of 7s16d1 → 6d2 and lead to the stabilization of two Th(IV)s in the ThC4-Th(C2)2 structure. It also reveals that the U species exhibit magnetic exchange coupling behavior in UxC8, for instance, as seen in the direct interaction of U2C8 and the superexchange pathway of U3C8, which effectively stabilizes their low-spin states. This interpretation indicates that the geometric and electronic structures of AnxC8 species are largely influenced by the local magnetic moment and spin correlation.

6.
Nat Mater ; 23(1): 52-57, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38052935

RESUMO

Although metallic nanostructures have been attracting tremendous research interest in nanoscience and nanotechnologies, it is known that environmental attacks, such as surface oxidation, can easily initiate cracking on the surface of metals, thus deteriorating their overall functional/structural properties1-3. In sharp contrast, here we report that severely oxidized metallic glass nanotubes can attain an ultrahigh recoverable elastic strain of up to ~14% at room temperature, which outperform bulk metallic glasses, metallic glass nanowires and many other superelastic metals hitherto reported. Through in situ experiments and atomistic simulations, we reveal that the physical mechanisms underpinning the observed superelasticity can be attributed to the formation of a percolating oxide network in metallic glass nanotubes, which not only restricts atomic-scale plastic events during loading but also leads to the recovery of elastic rigidity on unloading. Our discovery implies that oxidation in low-dimensional metallic glasses can result in unique properties for applications in nanodevices.

7.
Adv Sci (Weinh) ; 11(3): e2304709, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38009798

RESUMO

Compared with individuals with hearing loss, tinnitus patients without hearing loss have more psychological or emotional problems. Tinnitus is closely associated to abnormal metabolism and function of the limbic system, a key brain region for emotion experience, but the underlying molecular mechanism remains unknown. Using whole-brain microvasculature dynamics imaging, the anterior cingulate cortex (ACC) is identified as a key brain region of limbic system involve in the onset of salicylate-induced tinnitus in mice. In the tinnitus group, there is enhanced purine metabolism, oxidative phosphorylation, and a distinct pattern of phosphorylation in glutamatergic synaptic pathway according to the metabolome profiles, quantitative proteomic, and phosphoproteomic data of mice ACC tissue. Electroencephalogram in tinnitus patients with normal hearing thresholds show that the functional connectivity between pregenual anterior cingulate cortex and the primary auditory cortex is significantly increased for high-gamma frequency band, which is positively correlated with the serum glutamate level. These findings indicate that ACC plays an important role in the pathophysiology of tinnitus by interacting with the primary auditory cortex and provide potential molecular targets in the ACC for tinnitus treatment.


Assuntos
Perda Auditiva , Zumbido , Humanos , Camundongos , Animais , Giro do Cíngulo/patologia , Zumbido/patologia , Proteômica , Eletroencefalografia
8.
Medicine (Baltimore) ; 102(42): e35691, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37861530

RESUMO

BACKGROUND: In order to overcome the shortcomings of common surgical fixation methods for Distal Tibiofibular Syndesmosis (DTS) injuries, which include the inability to exercise early, significant surgical trauma, and the risk of loosening and breakage of implants, we have designed and implemented a new technique using steel cable fixation to treat DTS injuries. METHODS: Twenty-six patients treated with steel cable fixation for DTS injury between March 2013 and March 2019 in the Second Hospital of Tangshan City trauma department were followed up to monitor the efficacy of treatment. There were 16 males and 10 females between the ages of 19 and 64, with a mean age of 41.81 ± 9.54 years. All patients were examined by X-ray and CT for 3 days before and after surgery. The patients were then reexamined by X-ray 6 and 9 weeks postoperatively, and by CT 1 year later. The treatment results were evaluated by comparing the distal tibiofibular anterior, middle, and posterior gap changes and the Baird-Jackson score. RESULTS: The 26 patients attained good postoperative repositioning, with a fracture healing time of 2.5 to 3 months. and the Baird-Jackson score was 96 ± 2.78. After surgery, the DTS gaps observed in the CT scans taken 3 days and 1 year postoperatively in all patients were significantly reduced compared to the preoperative measurements, with statistical significance (P < .05). However, when comparing the CT scans taken 1 year postoperatively to those at 3 days postoperatively, there was no significant change in the anterior gap. The middle and posterior gaps of DTS showed a slight increase with statistical significance (P < .05), but all measurements remained within the normal range. CONCLUSION: Steel cable fixation for DTS injury has the advantages of reliable fixation, early functional exercise, and reduction in the number of operations, and no adverse effects or complications were found.


Assuntos
Fraturas do Tornozelo , Traumatismos do Tornozelo , Masculino , Feminino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Articulação do Tornozelo/cirurgia , Fixação Interna de Fraturas/métodos , Fraturas do Tornozelo/cirurgia , Resultado do Tratamento , Traumatismos do Tornozelo/diagnóstico por imagem , Traumatismos do Tornozelo/cirurgia
9.
Artigo em Inglês | MEDLINE | ID: mdl-36752284

RESUMO

Recent breakthroughs in cell transplantation therapy have revealed the promising potential of bone marrow mesenchymal stem cells (BMSCs) for promoting the regeneration of growth plate cartilage injury. However, the high apoptosis rate and the uncertainty of the differentiation direction of cells often lead to poor therapeutic effects. Cells are often grown under three-dimensional (3D) conditions in vivo, and the stiffness and components of the extracellular matrix (ECM) are important regulators of stem cell differentiation. To this end, a 3D cartilage-like ECM hydrogel with tunable mechanical properties was designed and synthesized mainly from gelatin methacrylate (GM) and oxidized chondroitin sulfate (OCS) via dynamic Schiff base bonding under UV. The effects of scaffold stiffness and composition on the survival and differentiation of BMSCs in vitro were investigated. A rat model of growth plate injury was developed to validate the effect of the GMOCS hydrogels encapsulated with BMSCs on the repair of growth plate injury. The results showed that 3D GMOCS hydrogels with an appropriate modulus significantly promoted chondrogenic differentiation of BMSCs, and GMOCS/BMSC transplantation could effectively inhibit bone bridge formation and promote the repair of damaged growth plates. Accordingly, GMOCS/BMSC therapy can be engineered as a promising therapeutic candidate for growth plate injury.

10.
Nano Lett ; 23(4): 1211-1218, 2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-36748951

RESUMO

Interfacial atomic configuration and its evolution play critical roles in the structural stability and functionality of mixed zero-dimensional (0D) metal nanoparticles (NPs) and two-dimensional (2D) semiconductors. In situ observation of the interface evolution at atomic resolution is a vital method. Herein, the directional migration and structural evolution of Au NPs on anisotropic ReS2 were investigated in situ by aberration-corrected transmission electron microscopy. Statistically, the migration of Au NPs with diameters below 3 nm on ReS2 takes priority with greater probability along the b-axis direction. Density functional theory calculations suggest that the lower diffusion energy barrier enables the directional migration. The coalescence kinetics of Au NPs is quantitatively described by the relation of neck radius (r) and time (t), expressed as r2=Kt. Our work provides an atomic-resolved dynamic analysis method to study the interfacial structural evolution of metal/2D materials, which is essential to the study of the stability of nanodevices based on mixed-dimensional nanomaterials.

11.
Adv Healthc Mater ; 12(13): e2203306, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36708290

RESUMO

Photothermal hydrogel adhesives have yielded promising results for wound closure and infected wound treatment in recent years. However, photothermal hydrogel bioadhesives with on-demand removability without additional nanomaterials-based photothermal agents have rarely been reported in the literature. In this work, an injectable intrinsic photothermal hydrogel bioadhesive with an on-demand removal trait is developed through dynamic cross-linking of gelatin (Gel), tannic acid (TA) quinone, and borax for closing skin incisions and accelerating methicillin-resistant Staphylococcus aureus (MRSA) infected wound healing. The TA quinone containing polyphenol and quinone groups with multifunctional adhesiveness and intrinsic photothermal performance confer the hydrogel adhesive with near-infrared (NIR) responsive antibacterial activity. The cross-linking of pH-sensitive boronic ester (polyphenol-B) and Schiff base bonds endow the hydrogel with great self-healing capacity and on-demand removability. Moreover, the hydrogel possesses good biocompatibility, injectability, and hemostasis. The in vivo experiment in a rat cutaneous incision model and full-thickness MRSA-infected wound model indicate that the smart hydrogel can close wounds efficiently and treat infected ones, demonstrating its superiority in noninvasive treatment of cutaneous incisions and enhancing infected full-thickness wound healing.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Animais , Ratos , Hidrogéis/farmacologia , Antibacterianos/farmacologia , Polifenóis , Quinonas , Cicatrização
12.
Life (Basel) ; 14(1)2023 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-38255649

RESUMO

COCH (coagulation factor C homology) is one of the most frequently mutated genes of autosomal dominant non-syndromic hearing loss. Variants in COCH could cause DFNA9, which is characterized by late-onset hearing loss with variable degrees of vestibular dysfunction. In this study, we report a Chinese family with a novel COCH variant (c.1687delA) causing p.D544Vfs*3 in the cochlin. Comprehensive audiometric tests and vestibular function assessments were taken to acquire the phenotypic profile of the subjects. Next-generation sequencing was conducted and segregation analysis was carried out using Sanger sequencing. The proband presented mild vestibular symptoms and normal functional assessment results in almost every test, while the variant co-segregated with hearing impairment in the pedigree. The variant was located beyond the vWFA2 domain, which was predicted to affect the post-translational cleavage of the cochlin via molecular modeling analysis. Notably, in the overexpressing study, by transient transfecting the HEK 293T cells, we found that the p.D544Vfs*3 variant increased the formation of multimeric cochlin. Our result enriched the spectrum of DFNA9-linked pathological COCH variants and suggested that variants, causative of cochlin multimerization, could be related to DFNA9 with sensorineural hearing loss rather than serious vestibular symptoms.

13.
ACS Appl Mater Interfaces ; 14(49): 54488-54499, 2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36461925

RESUMO

Bioadhesives are widely used in a variety of medical settings due to their ease of use and efficient wound closure and repair. However, achieving both strong adhesion and removability/reusability is highly needed but challenging. Here, we reported an injectable mesoporous bioactive glass nanoparticle (MBGN)-incorporated biopolymer hydrogel bioadhesive that demonstrates a strong adhesion strength (up to 107.55 kPa) at physiological temperatures that is also removable and reusable. The incorporation of MBGNs in the biopolymer hydrogel significantly enhances the tissue adhesive strength due to an increased cohesive and adhesive property compared to the hydrogel adhesive alone. The detachment of bioadhesive results from temperature-induced weakening of interfacial adhesive strength. Moreover, the bioadhesive displays injectability, self-healing, and excellent biocompatibility. We demonstrate potential applications of the bioadhesive in vitro, ex vivo, and in vivo for hemostasis and intestinal leakage closure and accelerated skin wound healing compared to surgical wound closures. This work provides a novel design of strong and removable bioadhesives.


Assuntos
Adesivos , Adesivos Teciduais , Adesivos/farmacologia , Nanogéis , Hidrogéis/farmacologia , Adesivos Teciduais/farmacologia , Biopolímeros/farmacologia
14.
ACS Nano ; 16(12): 20770-20785, 2022 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-36412574

RESUMO

Preventing local tumor recurrence and simultaneously improving bone-tissue regeneration are in great demand for osteosarcoma therapy. However, the current therapeutic implants fail to selectively suppress tumor growth and enhance osteogenesis, and antitumor therapy may compromise osseointegration of the bone implant. Here, based on the different responses of bone tumor cells and osteoblasts to different electric stimulations, we constructed ferroelectric BaTiO3 nanorod arrays (NBTO) on the surface of titanium implants with switchable dynamic and static electrical stimulation for selective bone-tumor therapy and bone tissue regeneration. Polarized NBTO (PNBTO) generated a sustained dynamic electrical stimulus in response to wireless ultrasonic irradiation ("switch-on"), which disrupted the orientation of the spindle filaments of the tumor cell, blocked the G2/M phase of mitosis, and ultimately led to tumor cell death, whereas it had almost no cytotoxic effect on normal bone cells. Under the switch-off state, PNBTO with a high surface potential provided static electrical stimulation, accelerating osteogenic differentiation of mesenchymal stem cells and enhancing the quality of bone regeneration both in vitro and in vivo. This study broadens the biomedical potential of electrical stimulation therapy and provides a comprehensive and clinically feasible strategy for the overall treatment and tissue regeneration in osteosarcoma.


Assuntos
Osteogênese , Osteossarcoma , Humanos , Osso e Ossos , Próteses e Implantes , Diferenciação Celular , Osteossarcoma/terapia , Estimulação Elétrica , Titânio/farmacologia
15.
Comput Biol Med ; 147: 105763, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35777086

RESUMO

Conventional size object detection has been extensively studied, whereas researches concerning ultrasmall object detection are rare due to lack of dataset. Here, considering that the stapes in the ear is the smallest bone in our body, we have collected the largest stapedial otosclerosis detection dataset from 633 stapedial otosclerosis patients and 269 normal cases to promote this direction. Nevertheless, noisy classification labels in our dataset are inevitable due to various subjective and objective factors, and this situation prevails in various fields. In this paper, we propose a novel and general noise tolerant loss function named Adaptive Cross Entropy (ACE) which needs no fine-tuning of hyperparameters for training with noisy labels. We provide both theoretical and empirical analyses for the proposed ACE loss and demonstrate its effectiveness in multiple public datasets. Besides, we find high-resolution representations crucial for ultrasmall object detection and present an auxiliary backbone called W-Net to address it accordingly. Extensive experiments demonstrate that the proposed ACE loss is able to boost the diagnosis performance under noisy label setting by a large margin. Furthermore, our W-Net can help extract sufficient high-resolution representations specialized for ultrasmall objects and achieve even better results. Hopefully, our work could provide more clues for future research on ultrasmall object detection and learning with noisy labels.


Assuntos
Otosclerose , Entropia , Humanos , Estribo , Tomografia Computadorizada por Raios X/métodos
16.
Adv Sci (Weinh) ; 9(13): e2105586, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35253394

RESUMO

Electroconductive hydrogels are very attractive candidates for accelerated spinal cord injury (SCI) repair because they match the electrical and mechanical properties of neural tissue. However, electroconductive hydrogel implantation can potentially aggravate inflammation, and hinder its repair efficacy. Bone marrow stem cell-derived exosomes (BMSC-exosomes) have shown immunomodulatory and tissue regeneration effects, therefore, neural tissue-like electroconductive hydrogels loaded with BMSC-exosomes are developed for the synergistic treatment of SCI. These exosomes-loaded electroconductive hydrogels modulate microglial M2 polarization via the NF-κB pathway, and synergistically enhance neuronal and oligodendrocyte differentiation of neural stem cells (NSCs) while inhibiting astrocyte differentiation, and also increase axon outgrowth via the PTEN/PI3K/AKT/mTOR pathway. Furthermore, exosomes combined electroconductive hydrogels significantly decrease the number of CD68-positive microglia, enhance local NSCs recruitment, and promote neuronal and axonal regeneration, resulting in significant functional recovery at the early stage in an SCI mouse model. Hence, the findings of this study demonstrate that the combination of electroconductive hydrogels and BMSC-exosomes is a promising therapeutic strategy for SCI repair.


Assuntos
Exossomos , Traumatismos da Medula Espinal , Animais , Axônios/metabolismo , Exossomos/metabolismo , Hidrogéis , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/terapia
17.
Nanoscale ; 14(14): 5545-5550, 2022 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-35343558

RESUMO

Controlling the electronic properties of complex oxides by an external stimulus is of significant importance for exploring exotic quantum states and developing modern electronic devices with low-level energy consumption. Here, we demonstrate the electro-photo double control of electronic transport for Mott insulating LaVO3 thin films deposited onto ferroelectric 0.7Pb(Mg1/3Nb2/3)O3-0.3PbTiO3 substrates. An electrically driven linear electroresistance effect is acquired at room temperature through the converse piezoelectric response, which can be optically regulated by 79%. Furthermore, the visible light-activated photoresistance response can be efficiently tuned by piezo strain. These results demonstrate that the strain-excited effect and photo-generated effect strongly correlated with each other, mediated by lattice-charge-orbital coupling. Our work points to an effective strategy for realizing the coupled straintronic-optoelectronic effect in hybrid correlated oxide/ferroelectric systems and delivering multi-field tunable low-dissipation versatile electronic and photonic devices.

18.
Phys Rev Lett ; 128(1): 015701, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35061460

RESUMO

Metals usually have three crystal structures: face-centered cubic (fcc), body-centered cubic (bcc), and hexagonal-close packed (hcp) structures. Typically, metals exhibit only one of these structures at room temperature. Mechanical processing can cause phase transition in metals, however, metals that exhibit all the three crystal structures have rarely been approached, even when hydrostatic pressure or shock conditions are applied. Here, through in situ observation of the atomic-scale bending and tensile process of ∼5 nm-sized Ag nanowires (NWs), we show that bending is an effective method to facilitate fcc-structured Ag to access all the above-mentioned structures. The process of transitioning the fcc structure into a bcc structure, then into an hcp structure, and finally into a re-oriented fcc structure under bending has been witnessed in its entirety. This re-oriented fcc structure is twin-related to the matrix, which leads to twin nucleation without the need for partial dislocation activities. The results of this study advance our understanding of the deformation mechanism of small-sized fcc metals.

19.
Bioact Mater ; 7: 98-111, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34466720

RESUMO

Injectable biomaterial-based treatment is a promising strategy to enhance tissue repair after traumatic spinal cord injury (SCI) by bridging cavity spaces. However, there are limited reports of injectable, electroconductive hydrogels with self-healing properties being employed for the treatment of traumatic SCI. Hence, a natural extracellular matrix (ECM) biopolymer (chondroitin sulphate and gelatin)-based hydrogel containing polypyrrole, which imparted electroconductive properties, is developed for traumatic SCI repair. The resulting hydrogels showed mechanical (~928 Pa) and conductive properties (4.49 mS/cm) similar to natural spinal cord tissues. Moreover, the hydrogels exhibited shear-thinning and self-healing abilities, which allows it to be effectively injected into the injury site and to fill the lesion cavity to accelerate the tissue repair of traumatic SCI. In vitro, electroconductive ECM hydrogels promoted neuronal differentiation, enhanced axon outgrowth, and inhibited astrocyte differentiation. The electroconductive ECM hydrogel activated endogenous neural stem cell neurogenesis in vivo (n = 6), and induced myelinated axon regeneration into the lesion site via activation of the PI3K/AKT and MEK/ERK pathways, thereby achieving significant locomotor function restoration in rats with spinal cord injury (p < 0.001, compared to SCI group). Overall, the injectable self-healing electroconductive ECM-based hydrogels developed in this study are ideal biomaterials for treatment of traumatic SCI.

20.
Adv Healthc Mater ; 11(1): e2101556, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34648694

RESUMO

The critical effects that impair diabetic wound healing are characterized by poor vascularization and severe peripheral neuropathy. Current management strategies for diabetic wound healing are unsatisfactory, due to the paucity of neurovascular regeneration at the wound site. Importantly, conductivity in skin tissue is reported to be essential for modulating myriad biological processes especially vascular and nerve regeneration. Herein, an extracellular matrix (ECM)-based conductive dressing is synthesized from an interpenetrating polymer network hydrogel composed of gelatin methacryloyl, oxidized chondroitin sulfate (OCS), and OCS-polypyrrole conductive nanoparticles that can promote diabetic wound repairing by enhancing local neurovascular regeneration. The conductive hydrogels combine the advantageous features of water-swollen hydrogels with conductive polymers (CPs) to provide tissue-matching electrical conductivity and mechanical properties for neurovascular regeneration. In vitro and in vivo studies show that the conductive hydrogel can promote neurovascular regeneration by increasing intracellular Ca2+ concentration, which subsequently promotes phosphorylation of proteins in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathways. Furthermore, the conductive hydrogel stimulates full-thickness diabetic wound repair on day 14 by promoting local neurovascular regeneration and collagen deposition. These findings corroborate that the ECM-based conductive interpenetrating network hydrogel dressing significantly promotes wound repairing due to its neurovascular regeneration properties, suggesting that they are suitable candidates for diabetic wound repair.


Assuntos
Diabetes Mellitus , Hidrogéis , Condutividade Elétrica , Matriz Extracelular , Gelatina , Humanos , Metacrilatos , Fosfatidilinositol 3-Quinases , Polímeros , Pirróis
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