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1.
Bioact Mater ; 39: 336-353, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38827171

RESUMO

While mild hyperthermia holds great potential in the treatment of solid tumors, the thermal stress-triggered self-repairing autophagy significantly compromises its efficacy. To circumvent this obstacle, an injectable hydrogel (NO-Gel) composed of thermosensitive poly(ethylene glycol)-polypeptide copolymers modified with abundant NO donors on their side chains is developed. Meanwhile, ferrimagnetic Zn0.5Fe2.5O4 magnetic nanoparticles (MNPs) with high magnetic-heat conversion efficiency are synthesized and loaded into NO-Gel to obtain MNPs@NO-Gel. The MNPs@NO-Gel system exhibits a sol-gel transition upon heating, and has the ability to perform multiple magnetic hyperthermia therapy (MHT) after only one administration due to the even distribution and strong immobilization of MNPs in NO-Gel. NO can be continuously liberated from NO-Gel and this process is markedly accelerated by MHT. Additionally, MNPs@NO-Gel maintains its integrity in vivo for over one month and the released MNPs are metabolized by the spleen. After a single administration of MNPs@NO-Gel at the tumor site, three mild MHT treatments with similar effects are fulfilled, and the sufficient supply of NO effectively inhibits MHT-induced autophagic flux via blocking the formation of autophagosomes and synchronously destroying lysosomes, thereby substantially boosting the efficacy of mild MHT. As a consequence, CT-26 colon tumors are completely eliminated without causing severe side-effects.

2.
ACS Appl Bio Mater ; 7(6): 3997-4006, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38815185

RESUMO

Epithelial-mesenchymal transition (EMT) is critical for tumor invasion and many other cell-relevant processes. While much progress has been made about EMT, no report concerns the EMT of cells on topological biomaterial interfaces with significant nuclear deformation. Herein, we prepared a poly(lactide-co-glycolide) micropillar array with an appropriate dimension to enable significant deformation of cell nuclei and examined EMT of a human lung cancer epithelial cell (A549). We show that A549 cells undergo serious nuclear deformation on the micropillar array. The cells express more E-cadherin and less vimentin on the micropillar array than on the smooth surface. After transforming growth factor-ß1 (TGF-ß1) treatment, the expression of E-cadherin as an indicator of the epithelial phenotype is decreased and the expression of vimentin as an indicator of the mesenchymal phenotype is increased for the cells both on smooth surfaces and on micropillar arrays, indicating that EMT occurs even when the cell nuclei are deformed and the culture on the micropillar array more enhances the expression of vimentin. Expression of myosin phosphatase targeting subunit 1 is reduced in the cells on the micropillar array, possibly affecting the turnover of myosin light chain phosphorylation and actin assembly; this makes cells on the micropillar array prefer the epithelial-like phenotype and more sensitive to TGF-ß1. Overall, the micropillar array exhibits a promoting effect on the EMT.


Assuntos
Materiais Biocompatíveis , Transição Epitelial-Mesenquimal , Humanos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Vimentina/metabolismo , Células A549 , Teste de Materiais , Tamanho da Partícula , Caderinas/metabolismo , Propriedades de Superfície
3.
Heart Views ; 25(1): 46-49, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38774555

RESUMO

Patients who suffer from severe tricuspid regurgitation (TR) and who are at high surgical risk have no standard care therapy. Therefore, minimally invasive and safer methods are sought. K-clip™, the first ultrasound-positioned interventional tricuspid annuloplasty instrument intended for percutaneous transcatheter repair. We report a patient with severe functional TR and high surgical risk who underwent K-clip™ tricuspid annuloplasty under echocardiography and fluoroscopy guidance.

4.
Biofabrication ; 16(3)2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38569492

RESUMO

Tissue engineering has emerged as an advanced strategy to regenerate various tissues using different raw materials, and thus it is desired to develop more approaches to fabricate tissue engineering scaffolds to fit specific yet very useful raw materials such as biodegradable aliphatic polyester like poly (lactide-co-glycolide) (PLGA). Herein, a technique of 'wet 3D printing' was developed based on a pneumatic extrusion three-dimensional (3D) printer after we introduced a solidification bath into a 3D printing system to fabricate porous scaffolds. The room-temperature deposition modeling of polymeric solutions enabled by our wet 3D printing method is particularly meaningful for aliphatic polyester, which otherwise degrades at high temperature in classic fuse deposition modeling. As demonstration, we fabricated a bilayered porous scaffold consisted of PLGA and its mixture with hydroxyapatite for regeneration of articular cartilage and subchondral bone. Long-termin vitroandin vivodegradation tests of the scaffolds were carried out up to 36 weeks, which support the three-stage degradation process of the polyester porous scaffold and suggest faster degradationin vivothanin vitro. Animal experiments in a rabbit model of articular cartilage injury were conducted. The efficacy of the scaffolds in cartilage regeneration was verified through histological analysis, micro-computed tomography (CT) and biomechanical tests, and the influence of scaffold structures (bilayerversussingle layer) onin vivotissue regeneration was examined. This study has illustrated that the wet 3D printing is an alternative approach to biofabricate tissue engineering porous scaffolds based on biodegradable polymers.


Assuntos
Cartilagem Articular , Animais , Coelhos , Porosidade , Microtomografia por Raio-X , Temperatura , Alicerces Teciduais/química , Engenharia Tecidual/métodos , Polímeros , Poliésteres , Impressão Tridimensional
5.
Adv Healthc Mater ; 13(16): e2303395, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38554036

RESUMO

In the last 30 years, there are ≈60 000 publications about electrospun nanofibers, but it is still unclear whether nanoscale fibers are really necessary for electrospun tissue engineering scaffolds. The present report puts forward this argument and reveals that compared with electrospun nanofibers, microfibers with diameter of ≈3 µm (named as "oligo-micro fiber") are more appropriate for tissue engineering scaffolds owing to their better cell infiltration ability caused by larger pores with available nuclear deformation. To further increase pore sizes, electrospun poly(ε-caprolactone) (PCL) scaffolds are fabricated using latticed collectors with meshes. Fiber orientation leads to sufficient mechanical strength albeit increases porosity. The latticed scaffolds exhibit good biocompatibility and improve cell infiltration. Under aortic conditions in vitro, the performances of latticed scaffolds are satisfactory in terms of the acute systolic hemodynamic functionality, except for the higher regurgitation fraction caused by the enlarged pores. This hierarchical electrospun scaffold with sparse fibers in macropores and oligo-micro fibers in filaments provides new insights into the design of tissue engineering scaffolds, and tissue engineering may provide living heart valves with regenerative capabilities for patients with severe valve disease in the future.


Assuntos
Nanofibras , Poliésteres , Engenharia Tecidual , Alicerces Teciduais , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Nanofibras/química , Poliésteres/química , Animais , Humanos , Valvas Cardíacas/fisiologia , Porosidade , Próteses Valvulares Cardíacas , Materiais Biocompatíveis/química
6.
Pharmaceutics ; 16(1)2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38258085

RESUMO

Atherosclerotic disease is a substantial global burden, and existing treatments, such as statins, are recommended to lower low-density lipoprotein cholesterol (LDL-C) levels and inhibit the progression of atherosclerosis. However, side effects, including gastrointestinal unease, potential harm to the liver, and discomfort in the muscles, might be observed. In this study, we propose a novel method using periodic mesoporous silica nanoparticles (PMS) to create heparin-modified PMS (PMS-HP) with excellent biocompatibility, enabling selective removal of LDL-C from the blood. In vitro, through the introduction of PMS-HP into the plasma of mice, we observed that, compared to PMS alone, PMS-HP could selectively adsorb LDL-C while avoiding interference with valuable components such as plasma proteins and high-density lipoprotein cholesterol (HDL-C). Notably, further investigations revealed that the adsorption of LDL-C by PMS-HP could be well-fitted to quasi-first-order (R2 = 0.993) and quasi-second-order adsorption models (R2 = 0.998). Likewise, in vivo, intravenous injection of PMS-HP enabled targeted LDL-C adsorption (6.5 ± 0.73 vs. 8.6 ± 0.76 mM, p < 0.001) without affecting other plasma constituents, contributing to reducing intravascular plaque formation (3.66% ± 1.06% vs. 1.87% ± 0.79%, p < 0.05) on the aortic wall and inhibiting vascular remodeling (27.2% ± 6.55% vs. 38.3% ± 1.99%, p < 0.05). Compared to existing lipid adsorption techniques, PMS-HP exhibited superior biocompatibility and recyclability, rendering it valuable for both in vivo and in vitro applications.

7.
Regen Biomater ; 11: rbad112, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38173765

RESUMO

Corrodible metals are the newest kind of biodegradable materials and raise a new problem of the corrosion products. However, the removal of the precipitated products has been unclear and even largely ignored in publications. Herein, we find that albumin, an abundant macromolecule in serum, enhances the solubility of corrosion products of iron in blood mimetic Hank's solution significantly. This is universal for other main biodegradable metals such as magnesium, zinc and polyester-coated iron. Albumin also influences corrosion rates in diverse trends in Hank's solution and normal saline. Based on quantitative study theoretically and experimentally, both the effects on corrosion rates and soluble fractions are interpreted by a unified mechanism, and the key factor leading to different corrosion behaviors in corrosion media is the interference of albumin to the Ca/P passivation layer on the metal surface. This work has illustrated that the interactions between metals and media macromolecules should be taken into consideration in the design of the next-generation metal-based biodegradable medical devices in the formulism of precision medicine. The improved Hank's solution in the presence of albumin and with a higher content of initial calcium salt is suggested to access biodegradable metals potentially for cardiovascular medical devices, where the content of calcium salt is calculated after consideration of chelating of calcium ions by albumin, resulting in the physiological concentration of free calcium ions.

8.
Biomaterials ; 304: 122411, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38061184

RESUMO

Poly(l-lactide) (PLLA) is an important candidate raw material of the next-generation biodegradable stent for percutaneous coronary intervention, yet how to make a polyester stent with sufficient mechanical strength and relatively fast biodegradation gets to be a dilemma. Herein, we put forward a hybrid interpenetrating network (H-IPN) strategy to resolve this dilemma. As such, we synthesize a multi-functional biodegradable macromer of star-like poly(d,l-lactide-co-ɛ-caprolactone) with six acrylate end groups, and photoinitiate it, after mixing with linear PLLA homopolymer, to trigger the free radical polymerization. The resultant crosslinked polymer blend is different from the classic semi-interpenetrating network, and partial chemical crosslinking occurs between the linear polymer and the macromer network. Combined with the tube blow molding and the postprocessing laser cutting, we fabricate a semi-crosslinked-polyester biodegradable coronary stent composed of H-IPN, which includes a physical network of polyester spherulites and a chemical crosslinking network of copolyester macromers and a part of homopolymers. Compared with the currently main-stream PLLA stent in research, this H-IPN stent realizes a higher and more appropriate biodegradation rate while maintaining sufficient radial strength. A series of polymer chemistry, polymer physics, polymer processing, and in vitro and in vivo biological assessments of medical devices have been made to examine the H-IPN material. The interventional implanting of the H-IPN stent into aorta abdominalis of rabbits and the follow-ups to 12 months have confirmed the safety and effectiveness.


Assuntos
Poliésteres , Polímeros , Animais , Coelhos , Poliésteres/química , Stents
9.
Expert Rev Cardiovasc Ther ; 21(11): 877-885, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37983042

RESUMO

INTRODUCTION: Tricuspid regurgitation (TR) is one of the most prevalent types of valvular heart disease linked to poor prognosis in patients with heart failure and is usually ignored. TR has received considerable attention due to the progressive advancements in transcatheter therapies in recent years. AREAS COVERED: With relatively solid data and rapid technological advancements, tricuspid transcatheter edge-to-edge repair (T-TEER) is the most frequently employed in a series of tricuspid transcatheter interventional treatments for TR. However, the efficacy and technical benefits of T-TEER are limited because of the unique anatomical characteristics and pathological mechanisms of the tricuspid valve. The aim of this review is to summarize reported data on current status of T-TEER and to provide an expert opinion regarding the challenges it is now experiencing and future development direction and approach. EXPERT OPINION: T-TEER is a significant treatment for TR, but its effectiveness and technical promotion are limited due to the tricuspid valve unique anatomical characteristics and pathological mechanisms. The selection criteria for suitable patients, the choice of when to intervene, device innovation, the advancement of ultrasound technology, and the volume of evidence in evidence-based medicine all indicate that the disorder of TR will eventually be better treated and understood.


Assuntos
Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Tricúspide , Humanos , Resultado do Tratamento , Cateterismo Cardíaco , Valva Tricúspide/cirurgia , Insuficiência da Valva Tricúspide/cirurgia
10.
ACS Appl Mater Interfaces ; 15(36): 42113-42129, 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37639647

RESUMO

Local anesthetics are important for the treatment of postoperative pain. Since a single injection of the solution of a drug such as bupivacaine (BUP) works only for a few hours, it is much required to develop a long-term injectable formulation that maintains its efficacy for more than 1 day. Herein, an intelligent copolymer hydrogel loaded with BUP microcrystals was invented. The biodegradable block copolymer was synthesized by us and composed of a central hydrophilic poly(ethylene glycol) (PEG) block and two hydrophobic poly(lactide-co-glycolide) (PLGA) blocks. The aqueous system of the amphiphilic copolymer underwent a sol-gel transition between room temperature and body temperature and, thus, physically gelled after injection. Considering the decrease of solubility of BUP with the increase of pH and the internal acidic environment due to the hydrolysis of PLGA, calcium carbonate (CaCO3) powder was introduced as a pH regulator. Then, the internal pH was found to be nearly neutral and many BUP microcrystals were dispersed in the gel network. In this way, BUP had achieved a sustained release out of the thermogel. The maximum possible effect (MPE) in a rat sciatic nerve blockade model was used to describe the sensory blockade effect. In vivo analgesic effects evaluated with a hot plate experiment of rats demonstrated that the thermogel encapsulated with BUP microcrystal and CaCO3 powder significantly prolonged analgesia up to 44 h, the duration time with respect to 50% MPE. The intramuscularly injected implant exhibited biocompatibility in histological analyses. Besides, the untreated leg of the rats was not influenced by the treated leg, indicating no obvious systematic anesthesia of this hydrogel formulation. Such an intelligent and composite formulation represents a potential strategy for long-acting analgesia therapy.


Assuntos
Analgesia , Hidrogéis , Animais , Ratos , Hidrogéis/farmacologia , Pós , Manejo da Dor , Bupivacaína , Concentração de Íons de Hidrogênio
11.
Nanoscale Adv ; 5(16): 4286-4297, 2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37560424

RESUMO

The integration of the properties of silicon nano crystallinity with silica mesoporosity provides a wealth of new opportunities for emerging biomedicine. Cholesterol (CHO) and triglyceride (TG) levels have always been a challenge for cardiologists in the treatment of patients with chronic coronary artery disease (CAD). For patients with hyperlipidemia, statins and other lipid-lowering drugs are currently recommended. It should be noted, however, that significant side effects have been reported in the treatments, including liver damage, muscle pain, etc. We here found that our previously produced periodic mesoporous nanocrystalline silicon-silica, meso-ncSi/SiO2 (PMS), a nanocomposite material, has the properties of lowering CHO and TG, and is associated with better safety and biocompatibility compared to existing lipid-lowering drugs. After being incubated with PMS for 2 hours, CHO and TG levels in blood were significantly lower than before. In addition, CHO and TG adsorbed on with PMS could also be extracted and released, contributing to the recovery and recycling of PMS.

12.
Regen Biomater ; 10: rbad056, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37397871

RESUMO

Expanded polytetrafluoroethylene (ePTFE) is promising in biomedical fields such as covered stents and plastic surgery owing to its excellent biocompatibility and mechanical properties. However, ePTFE material prepared by the traditional biaxial stretching process is with thicker middle and thinner sides due to the bowing effect, which poses a major problem in industrial-scale fabrication. To solve this problem, we design an olive-shaped winding roller to provide the middle part of the ePTFE tape with a greater longitudinal stretching amplitude than the two sides, so as to make up for the excessive longitudinal retraction tendency of the middle part when it is transversely stretched. The as-fabricated ePTFE membrane has, as designed, uniform thickness and node-fibril microstructure. In addition, we examine the effects of mass ratio of lubricant to PTFE powder, biaxial stretching ratio and sintering temperature on the performance of the resultant ePTFE membranes. Particularly, the relation between the internal microstructure of the ePTFE membrane and its mechanical properties is revealed. Besides stable mechanical properties, the sintered ePTFE membrane exhibits satisfactory biological properties. We make a series of biological assessments including in vitro hemolysis, coagulation, bacterial reverse mutation and in vivo thrombosis, intracutaneous reactivity test, pyrogen test and subchronic systemic toxicity test; all of the results meet the relevant international standards. The muscle implantation of the sintered ePTFE membrane into rabbits indicates acceptable inflammatory reactions of our sintered ePTFE membrane fabricated on industrial scale. Such a medical-grade raw material with the unique physical form and condensed-state microstructure is expected to afford an inert biomaterial potentially for stent-graft membrane.

13.
Methods Mol Biol ; 2689: 65-70, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37430047

RESUMO

Micropatterned substrate is a unique method for studying cell biology at the single-cell level. Using photolithography to create binary patterns of cell-adherent peptide surrounding by non-fouling cell-repellent poly(ethylene glycol) (PEG) hydrogel, this patterning method allows for controlling cell attachment with desired sizes and shapes up to 19 days. Here we provide the detailed procedure of fabrication for such patterns. This method will allow monitoring of prolonged reaction of single cells such as cell differentiation upon induction or time-resolved apoptosis stimulated by drug molecules for cancer treatment.


Assuntos
Apoptose , Junções Célula-Matriz , Diferenciação Celular , Hidrogéis , Polietilenoglicóis
14.
Molecules ; 28(13)2023 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-37446569

RESUMO

Direct current (DC) power transmission systems have received great attention because it can easily integrate many types of renewable energies and have low energy loss in long-distance and large-capacity power transmission for electricity global sharing. Nanoparticles (NPs) have a positive effect on the insulation properties of polymers, but weak interaction between NPs and polymer matrix greatly decreases the effort of NPs on the enhancement of insulation properties, and thereby limits its engineering application. In this work, grafting strategy was used to link the modified NPs and polymer matrix to improve their interactions. Silica NPs (SiO2-NPs) were modified by 3-(methacrylyloxy) propyl-trimethoxysilane (MPS) to introduce highly active groups on the SiO2-NPs surface, followed by the pre-irradiated linear low-density polyethylene (LLDPE) being easily grafted onto the MPS modified SiO2-NPs (MPS-SiO2-NPs) in the melt blending process to obtain LLDPE-g-MPS-SiO2-NPs nanocomposites. Fourier-transform infrared (FT-IR) spectrum and X-ray photoelectron spectroscopy (XPS) confirm the successful incorporation of MPS into SiO2-NPs. Transmission electron microscopy (TEM) verifies that the modified SiO2-NPs exhibits more uniform distribution. The rheology result shows that the interaction between MPS-SiO2-NPs and LLDPE significantly improves. More importantly, the LLDPE-g-MPS-SiO2-NPs nanocomposites displays superior DC breakdown strength to that fabricated by conventional modification methods. When the addition of MPS-SiO2-NPs is 0.1 wt%, the highest DC breakdown strength values of 525 kV/mm and 372 kV/mm are obtained at 30 °C and 70 °C, respectively, and high DC breakdown strength can be well maintained in a wide loading range of NPs.


Assuntos
Nanopartículas , Polietileno , Dióxido de Silício/química , Espectroscopia de Infravermelho com Transformada de Fourier , Nanopartículas/química , Polímeros
15.
Biomater Res ; 27(1): 61, 2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37370127

RESUMO

BACKGROUND: Good osseointegration is the key to the long-term stability of bone implants. Thermoplastic polyetheretherketone (PEEK) has been widely used in orthopedics; however, its inherent biological inertia causes fibrous tissue to wrap its surface, which leads to poor osseointegration and thus greatly limits its clinical applications. METHODS: Herein, we developed a facile yet effective surface modification strategy. A commonly used sulfonation coupled with "cold pressing" treatment in the presence of porogenic agent formed a three-dimensional hierarchical porous structure on PEEK surface. Subsequently, the effects of porous surface on the in vitro adhesion, proliferation and differentiation of rat bone marrow-derived mesenchymal stem cells (BMSCs) were evaluated. Finally, the osteoinduction and osseointegration of surface-porous PEEK implant were examined in the rat distal femoral defect model. RESULTS: In vitro results showed that the surface modification did not significantly affect the mechanical performance and cytocompatibility of PEEK substance, and the porous structure on the modified PEEK substrate provided space for cellular ingrowth and enhanced osteogenic differentiation and mineralization of BMSCs. In vivo tests demonstrated that the surface-porous PEEK implant could effectively promote new bone formation and had higher bone-implant contact rate, thereby achieving good bone integration with the surrounding host bone. In addition, this modification technique was also successfully demonstrated on a medical PEEK interbody fusion cage. CONCLUSION: The present study indicates that topological morphology plays a pivotal role in determining implant osseointegration and this facile and effective modification strategy developed by us is expected to achieve practical applications quickly.

16.
Nat Nanotechnol ; 18(9): 1085-1093, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37142709

RESUMO

High rates of ligament damage require replacements; however, current synthetic materials have issues with bone integration leading to implant failure. Here we introduce an artificial ligament that has the required mechanical properties and can integrate with the host bone and restore movement in animals. The ligament is assembled from aligned carbon nanotubes formed into hierarchical helical fibres bearing nanometre and micrometre channels. Osseointegration of the artificial ligament is observed in an anterior cruciate ligament replacement model where clinical polymer controls showed bone resorption. A higher pull-out force is found after a 13-week implantation in rabbit and ovine models, and animals can run and jump normally. The long-term safety of the artificial ligament is demonstrated, and the pathways involved in integration are studied.


Assuntos
Ligamento Cruzado Anterior , Nanotubos de Carbono , Ovinos , Animais , Coelhos , Ligamento Cruzado Anterior/cirurgia , Fibra de Carbono , Próteses e Implantes
17.
Regen Biomater ; 10: rbad035, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37206162

RESUMO

Magnetic resonance imaging (MRI) is a promising non-invasive method to assess cartilage regeneration based on the quantitative relationship between MRI features and concentrations of the major components in the extracellular matrix (ECM). To this end, in vitro experiments are performed to investigate the relationship and reveal the underlying mechanism. A series of collagen (COL) and glycosaminoglycan (GAG) solutions at different concentrations are prepared, and T1 and T2 relaxation times are measured with or without a contrast agent (Gd-DTPA2-) by MRI. Fourier transform infrared spectrometry is also used to measure the contents of biomacromolecule-bound water and other water, allowing theoretical derivation of the relationship between biomacromolecules and the resulting T2 values. It has been revealed that the MRI signal in the biomacromolecule aqueous systems is mainly influenced by the protons in hydrogens of biomacromolecule-bound water, which we divide into inner-bound water and outer-bound water. We have also found that COL results in higher sensitivity of bound water than GAG in T2 mapping. Owing to the charge effect, GAG regulates the penetration of the contrast agent during dialysis and has a more significant effect on T1 values than COL. Considering that COL and GAG are the most abundant biomacromolecules in the cartilage, this study is particularly useful for the real-time MRI-guided assessment of cartilage regeneration. A clinical case is reported as an in vivo demonstration, which is consistent with our in vitro results. The established quantitative relation plays a critical academic role in establishing an international standard ISO/TS24560-1:2022 'Clinical evaluation of regenerative knee articular cartilage using delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and T2 mapping' drafted by us and approved by International Standard Organization.

18.
Biomaterials ; 298: 122139, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37148756

RESUMO

Magnetic hyperthermia therapy (MHT) is a promising new modality to deal with solid tumors, yet the low magnetic-heat conversion efficacy, magnetic resonance imaging (MRI) artifacts, easy leakage of magnetic nanoparticles, and thermal resistance are the main obstacles to expand its clinical applications. Herein, a synergistic strategy based on a novel injectable magnetic and ferroptotic hydrogel is proposed to overcome these bottlenecks and boost the antitumor efficacy of MHT. The injectable hydrogel (AAGel) exhibiting a sol-gel transition upon heating is made of arachidonic acid (AA)-modified amphiphilic copolymers. Ferrimagnetic Zn0.4Fe2.6O4 nanocubes with high-efficiency hysteresis loss mechanism are synthesized and co-loaded into AAGel with RSL3, a potent ferroptotic inducer. This system maintains the temperature-responsive sol-gel transition, and provides the capacity of multiple MHT and achieves accurate heating after a single injection owing to the firm anchoring and uniform dispersion of nanocubes in the gel matrix. The high magnetic-heat conversion efficacy of nanocubes coupled with the application of echo limiting effect avoids the MRI artifacts during MHT. Besides the function of magnetic heating, Zn0.4Fe2.6O4 nanocubes combined with multiple MHT can sustain supply of redox-active iron to generate reactive oxygen species and lipid peroxides and accelerate the release of RLS3 from AAGel, thus enhancing the antitumor efficacy of ferroptosis. In turn, the reinforced ferroptosis can alleviate the MHT-triggered thermal resistance of tumors by impairment of the protective heat shock protein 70. The synergy strategy achieves the complete elimination of CT-26 tumors in mice without causing local tumor recurrence and other severe side effects.


Assuntos
Ferroptose , Hipertermia Induzida , Nanopartículas , Neoplasias , Animais , Camundongos , Hipertermia Induzida/métodos , Hidrogéis , Neoplasias/terapia , Linhagem Celular Tumoral
19.
J Am Chem Soc ; 145(18): 10035-10044, 2023 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-37097713

RESUMO

Compared with traditional assay techniques, field-effect transistors (FETs) have advantages such as fast response, high sensitivity, being label-free, and point-of-care detection, while lacking generality to detect a wide range of small molecules since most of them are electrically neutral with a weak doping effect. Here, we demonstrate a photo-enhanced chemo-transistor platform based on a synergistic photo-chemical gating effect in order to overcome the aforementioned limitation. Under light irradiation, accumulated photoelectrons generated from covalent organic frameworks offer a photo-gating modulation, amplifying the response to small molecule adsorption including methylglyoxal, p-nitroaniline, nitrobenzene, aniline, and glyoxal when measuring the photocurrent. We perform testing in buffer, artificial urine, sweat, saliva, and diabetic mouse serum. The limit of detection is down to 10-19 M methylglyoxal, about 5 orders of magnitude lower than existing assay technologies. This work develops a photo-enhanced FET platform to detect small molecules or other neutral species with enhanced sensitivity for applications in fields such as biochemical research, health monitoring, and disease diagnosis.


Assuntos
Técnicas Biossensoriais , Líquidos Corporais , Animais , Camundongos , Técnicas Biossensoriais/métodos , Aldeído Pirúvico , Saliva , Transistores Eletrônicos
20.
Regen Biomater ; 10: rbad007, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36817974

RESUMO

Metal corrosion is important in the fields of biomedicine as well as construction and transportation etc. While most corrosion occurs inhomogeneously, there is so far no satisfactory parameter to characterize corrosion inhomogeneity. Herein, we employ the Poisson raindrop question to model the corrosion process and derive an equation to relate corrosion coverage and corrosion mass. The resultant equation is named coverage-mass equation, abbreviated as C-M equation. We also suggest corrosion mass at 50% coverage, termed as half-coverage mass M corro50%, as an inhomogeneity parameter to quantify corrosion inhomogeneity. The equation is confirmed and the half-coverage mass M corro50% is justified in our experiments of iron corrosion in five aqueous media, normal saline, phosphate-buffered saline, Hank's solution, deionized water and artificial seawater, where the former three ones are biomimetic and very important in studies of biomedical materials. The half-coverage mass M corro50% is proved to be more comprehensive and mathematically convergent than the traditional pitting factor. Iron corrosion is detected using visual observation, scanning electron microscopy with a build-in energy dispersive spectrometer, inductive coupled plasma emission spectrometry and electrochemical measurements. Both rates and inhomogeneity extents of iron corrosion are compared among the five aqueous media. The factors underlying the medium effects on corrosion rate and inhomogeneity are discussed and interpreted. Corrosion rates of iron in the five media differ about 7-fold, and half-coverage mass values differ about 300 000-fold. The fastest corrosion and the most significant inhomogeneity occur both in biomimetic media, but not the same one. The new equation (C-M equation) and the new quantity (half-coverage mass) are stimulating for dealing with a dynamic and stochastic process with global inhomogeneity including but not limited to metal corrosion. The findings are particularly meaningful for research and development of next-generation biodegradable materials.

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