RESUMEN
We develop soft and stretchable fatigue-resistant hydrogel optical fibers that enable optogenetic modulation of peripheral nerves in naturally behaving animals during persistent locomotion. The formation of polymeric nanocrystalline domains within the hydrogels yields fibers with low optical losses of 1.07 dB cm-1, Young's modulus of 1.6 MPa, stretchability of 200% and fatigue strength of 1.4 MPa against 30,000 stretch cycles. The hydrogel fibers permitted light delivery to the sciatic nerve, optogenetically activating hindlimb muscles in Thy1::ChR2 mice during 6-week voluntary wheel running assays while experiencing repeated deformation. The fibers additionally enabled optical inhibition of pain hypersensitivity in an inflammatory model in TRPV1::NpHR mice over an 8-week period. Our hydrogel fibers offer a motion-adaptable and robust solution to peripheral nerve optogenetics, facilitating the investigation of somatosensation.
Asunto(s)
Fibras Ópticas , Optogenética , Ratones , Animales , Hidrogeles , Actividad Motora , Nervio Ciático/fisiología , LocomociónRESUMEN
Osteosarcoma, the most common primary malignant bone tumor, is characterized by malignant cells producing osteoid or immature bone tissue. Most osteosarcoma patients require reconstructive surgery to restore the functional and structural integrity of the injured bone. Metal orthopedic implants are commonly used to restore the limb integrity in postoperative patients. However, conventional metal implants with a bioinert surface cannot inhibit the growth of any remaining cancer cells, resulting in a higher risk of cancer recurrence. Herein, we fabricate a selenium-doped TiO2 nanotube array (Se-doped TNA) film to modify the surface of medical pure titanium substrate, and evaluate the anti-tumor effect and biocompatibility of Se-doped TNA film. Moreover, we further explore the anti-tumor potential mechanism of Se-doped TNA film by studying the behaviors of human osteosarcoma cells in vitro. We provide a new pathway for achieving the anti-tumor function of orthopedic implants while keeping the biocompatibility, aiming to suppress the recurrence of osteosarcoma.
RESUMEN
The sole situation of semi-crystalline structure induced single performance remarkably limits the green cryogels in the application of soft devices due to uncontrolled freezing field. Here, a facile strategy for achieving multifunctionality of cryogels is proposed using total amorphization of polymer. Through precisely lowering the freezing point of precursor solutions with an antifreezing salt, the suppressed growth of ice is achieved, creating an unusually weak and homogenous aggregation of polymer chains upon freezing, thereby realizing the tunable amorphization of polymer and the coexistence of free and hydrogen bonding hydroxyl groups. Such multi-scale microstructures trigger the integrated properties of tissue-like ultrasoftness (Young's modulus <10 kPa) yet stretchability, high transparency (~92%), self-adhesion, and instantaneous self-healing (<0.3 s) for cryogels, along with superior ionic-conductivity, antifreezing (-58 °C) and water-retention abilities, pushing the development of skin-like cryogel electronics. These concepts open an attractive branch for cryogels that adopt regulated crystallization behavior for on-demand functionalities.
RESUMEN
Background: Research on the growth mechanism of titanium dioxide (TiO2) nanotube arrays fabricated by anodic oxidation is essential to achieve artificial control of the microstructure and to expand their applications. In our previous work, we reported the preparation of highly ordered large-diameter double-wall TiO2 nanotube arrays prepared by high voltage anodization. Methods: In this paper, we observed and analyzed the initial growth process of large-diameter double-wall TiO2 nanotube arrays anodized at 120 V in ethylene glycol electrolyte containing aluminum fluoride (NH4F) and water (H2O), such as the evolution of surface and cross-sectional morphologies, the influence of current density on growth rate, the transition process from nanoholes to nanotubes, and the evolution of dimples on the remaining substrate. Results: On the basis of our observations and inspirations from the existing viewpoints, we established growth models of large-diameter double-wall TiO2 nanotube arrays corresponding to different growth stages to explain the growth process. The growth rate of anodic oxide film changes accordingly with the current density. The compact anodic oxide film formed initially actually contains outer layer and inner layer, with no obvious interface between them. Then, the bottom even levels of the inner layer and outer layer bulge towards the substrate and become individual hemisphere-like structures. The inner layer becomes the outer wall, and the outer layer becomes inner wall. Eventually, V-shaped large-diameter and double-wall TiO2 nanotube arrays form. Conclusions: The results presented in this work are significant and provide a better understanding of the growth mechanism of large-diameter double-wall TiO2 nanotube arrays anodized by high voltage.
RESUMEN
Moderately regulating vascularization and immune microenvironment of wound site is necessary to achieve scarless wound healing of the skin. Herein, we have prepared an angiogenesis-promoting and scar-preventing band-aid with a core-shell structure, that consists of MXene-loaded nanofibers (MNFs) as the core and dopamine-hyaluronic acid hydrogel (H) as the shell (MNFs@V-H@DA) to encapsulate a growth factor (vascular endothelial growth factor, VEGF, abbreviated as V) and H2S donor (diallyl trisulfide, DATS, abbreviated as DA). The continuous release of DA from this system produced H2S, which would successfully induce macrophages to polarize into M2-lile phenotype, regulating the immune microenvironment and inhibiting an excessive inflammatory response at the wound sites. It is conducive to the proliferation of skin cells, facilitating the wound healing. In addition, an appropriate amount of VEGF can be released from the MXene nanofibrous skeleton by adjusting the time of near-infrared (NIR) light exposure, preventing excessive neovascularization and extracellular matrix deposition at the wound sites. Collectively, this NIR photothermal-responsive band-aid achieved scarless wound healing through gradient-controlled vascularization and a related immune sequential reaction of damaged skin tissue.
RESUMEN
Sporopollenin is a mechanically robust and chemically inert biopolymer that constitutes the outer protective exine layer of plant spores and pollen grains. Recent investigation of the molecular structure of pine sporopollenin revealed unique monomeric units and inter-unit linkages distinct from other previously known biopolymers, which could be harnessed for new material design. Herein, we report the bioinspired synthesis of a series of sporopollenin analogues. This exercise confirms large portions of our previously proposed pine sporopollenin structural model, while the measured chemical, thermal, and mechanical properties of the synthetic sporopollenins constitute favorable attributes of a new kind of robust material. This study explores a new design framework of robust materials inspired by natural sporopollenins, and provides insights and reagents for future elucidation and engineering of sporopollenin biosynthesis in plants.
RESUMEN
Hydrogen has been used to suppress tumor growth with considerable efficacy. Inhalation of hydrogen gas and oral ingestion of hydrogen-rich saline are two common systemic routes of hydrogen administration. We have developed a topical delivery method of hydrogen at targeted sites through the degradation of magnesium-based biomaterials. However, the underlying mechanism of hydrogen's role in cancer treatment remains ambiguous. Here, we investigate the mechanism of tumor cell apoptosis triggered by the hydrogen released from magnesium-based biomaterials. We find that the localized release of hydrogen increases the expression level of P53 tumor suppressor proteins, as demonstrated by the in vitro RNA sequencing and protein expression analysis. Then, the P53 proteins disrupt the membrane potential of mitochondria, activate autophagy, suppress the reactive oxygen species in cancer cells, and finally result in tumor suppression. The anti-tumor efficacy of magnesium-based biomaterials is further validated in vivo by inserting magnesium wire into the subcutaneous tumor in a mouse. We also discovered that the minimal hydrogen concentration from magnesium wires to trigger substantial tumor apoptosis is 91.2 µL/mm3 per day, which is much lower than that required for hydrogen inhalation. Taken together, these findings reveal the release of H2 from magnesium-based biomaterial exerts its anti-tumoral activity by activating the P53-mediated lysosome-mitochondria apoptosis signaling pathway, which strengthens the therapeutic potential of this biomaterial as localized anti-tumor treatment.
RESUMEN
Imaging-guided photothermal therapy (PTT)/photodynamic therapy (PDT) for cancer treatment are beneficial for precise localization of the malignant lesions and combination of multiple cell killing mechanisms in eradicating stubborn thermal-resistant cancer cells. However, overcoming the adverse impact of tumor hypoxia on PDT efficacy remains a challenge. Here, carrier-free nano-theranostic agents are developed (AIBME@IR780-APM NPs) for magnetic resonance imaging (MRI)-guided synergistic PTT/thermodynamic therapy (TDT). Two IR780 derivatives are synthesized as the subject of nanomedicine to confer the advantages for the nanomedicine, which are by feat of amphiphilic IR780-PEG to enhance the sterical stability and reduce the risk from reticuloendothelial system uptake, and IR780-ATU to chelate Mn2+ for T1 -weighted MRI. Dimethyl 2,2'-azobis(2-methylpropionate) (AIBME), acting as thermally decomposable radical initiators, are further introduced into nanosystems with the purpose of generating highly cytotoxic alkyl radicals upon PTT launched by IR780 under 808 nm laser irradiation. Therefore, the sequentially generated heat and alkyl radicals synergistically induce cell death via synergistic PTT/TDT, ignoring tumor hypoxia. Moreover, these carrier-free nano-theranostic agents present satisfactory biocompatibility, which could be employed as a powerful weapon to hit hypoxic tumors via MRI-guided oxygen-independent PTT and photonic TDT.
Asunto(s)
Neoplasias , Fotoquimioterapia , Línea Celular Tumoral , Humanos , Imagen por Resonancia Magnética/métodos , Neoplasias/tratamiento farmacológico , Neoplasias/terapia , Oxígeno/uso terapéutico , Fotoquimioterapia/métodos , Fototerapia/métodos , Nanomedicina Teranóstica/métodosRESUMEN
Biodegradable magnesium (Mg) implants spontaneously releasing therapeutic agents against tumors are an intriguing therapeutic approach for both tissue repair and tumor treatment. Anastomotic staples are extensively used for wound closure after surgical resection in patients with colorectal tumors. However, the safety of Mg anastomosis implants for intestinal closure and the effect of tumor suppression remain elusive. Here, we used a high-purity Mg staple to study these issues. Based on the results, we found that it has the potential to heal wounds produced after colorectal tumor resection while inhibiting relapse of residual tumor cells in vitro and in vivo. After implantation of Mg staples for 7 weeks in rabbits, the intestinal wound gradually healed with no adverse effects such as leakage or inflammation. Furthermore, the implanted Mg staples inhibit the growth of colorectal tumor cells and block migration to normal organs because of the increased concentration of Mg ions and released hydrogen. Such an antitumor effect is further confirmed by the in vitro cell experiments. Mg significantly induces apoptosis of tumor cells as well as inhibits cell growth and migration. Our work presents a feasible therapeutic opinion to design Mg anastomotic staples to perform wound healing and simultaneously release tumor suppressor elements in vivo to decrease the risk of tumor recurrence and metastasis.
Asunto(s)
Magnesio , Recurrencia Local de Neoplasia , Anastomosis Quirúrgica , Animales , Humanos , Magnesio/uso terapéutico , Recurrencia Local de Neoplasia/prevención & control , Conejos , Grapado Quirúrgico , SuturasRESUMEN
Gallbladder cancer can be difficult to detect in its early stages and is prone to metastasize, causing bile duct obstruction, which is usually treated by stent implantation in clinic. However, the commonly used biliary stents are non-degradable, which not only prone to secondary blockage, but also need to be removed by secondary surgery. Biodegradable magnesium (Mg) is expected to one of the promising candidates for degradable biliary stents due to its excellent physicochemical property and biocompatibility. In this work, we studied the influence of high-purity Mg wires on gallbladder cancer through in vitro and in vivo experiments and revealed that the degradation products of Mg could significantly inhibit the growth of gallbladder cancer cells and promote their apoptosis. Our findings indicate that Mg biliary stent possesses the function of draining bile and treating gallbladder cancer, suggesting that Mg has good application prospects in biliary surgery. STATEMENT OF SIGNIFICANCE: Current research and development of biomedical magnesium are mainly concentrated in the cardiovascular and orthopedics field. Degradable magnesium bile duct stents have great application prospects in the treatment of bile duct blockage caused by bile duct-related cancers. At present, the effect of magnesium implants on gallbladder cancer is not clear. Our work verified the effectiveness of magnesium wire implants in inhibiting gallbladder cancer through in vivo and in vitro experiments, and studied the effect of magnesium degradation products on gallbladder cancer cells from the perspective of cell proliferation, apoptosis and cycle. This study provided new understanding for the application of magnesium in biliary surgery.
Asunto(s)
Neoplasias de la Vesícula Biliar , Implantes Absorbibles , Conductos Biliares , Neoplasias de la Vesícula Biliar/tratamiento farmacológico , Humanos , Magnesio/farmacología , StentsRESUMEN
Lean alloy (low alloyed) is beneficial for long-term sustainable development of metal materials. Creating a nanocrystalline microstructure is a desirable approach to improve biodegradability and mechanical properties of lean biomedical Mg alloy, but it is nearly impossible to realize. In the present study, the bulk nanocrystalline Mg alloy (average grain size: ~70 nm) was successfully obtained by hot rolling process of a lean Mg-2wt.%Zn (Z2) alloy and both high strength ((223 MPa (YS) and 260 MPa (UTS)) and good corrosion resistance (corrosion rate in vivo: 0.2 mm/year) could be achieved. The microstructure evolution during the rolling process was analyzed and discussed. Several factors including large strain, fine grains, strong basal texture, high temperature and Zn segregation conjointly provided the possibility for the activation of pyramidal
RESUMEN
Microchannels in hydrogels play an essential role in enabling a smart contact lens. However, microchannels have rarely been created in commercial hydrogel contact lenses due to their sensitivity to conventional microfabrication techniques. Here, we report the fabrication of microchannels in poly(2-hydroxyethyl methacrylate) (poly(HEMA)) hydrogels that are used in commercial contact lenses with a three-dimensional (3D) printed mold. We investigated the corresponding capillary flow behaviors in these microchannels. We observed different capillary flow regimes in these microchannels, depending on their hydration level. In particular, we found that a peristaltic pressure could reinstate flow in a dehydrated channel, indicating that the motion of eye-blinking may help tears flow in a microchannel-containing contact lens. Colorimetric pH and electrochemical Na+ sensing capabilities were demonstrated in these microchannels. This work paves the way for the development of microengineered poly(HEMA) hydrogels for various biomedical applications such as eye-care and wearable biosensing.
Asunto(s)
Lentes de Contacto , Dispositivos Electrónicos Vestibles , Hidrogeles , Metacrilatos , Poliaminas , Polihidroxietil Metacrilato/análogos & derivadosRESUMEN
Because of excellent corrosion resistance, biocompatibility, high toughness, high hardness and moderate mechanical strength, Ta metals have excellent prospects for biomedical applications, especially implants. Many substances that interact directly with cells to affect their behavior have nanoscale topologies whose processes affect cells are also on the order of nanometer size. In this work, the surface of the nanotube structure is observed and the inner and outer diameters of the nanotubes are measured by scanning electron microscope (SEM). The contact angle is obtained by optical contact angle measuring device. Roughness is obtained by atomic force microscopy (AFM). Results show the inner diameter, outer diameter and tube thickness of the nanotubes increase linearly as the anodization voltage increases. At the macro level, as the nanotube inner diameter decreases, the roughness increases and the hydrophobicity increases. Biological results show on the structure of which the inner diameter of the nanotube is smaller, the viability and proliferation ability of the cells become stronger and the differentiation ability of the cells is also enhanced. Cells have more excellent morphology, including better spread of cells, more cell pseudopods and longer length of cell pseudopods.
Asunto(s)
Nanotubos/química , Tantalio , Animales , Adhesión Celular , Línea Celular , Ratones , Nanotubos/ultraestructura , Tamaño de la Partícula , Propiedades de Superficie , Tantalio/química , Tantalio/farmacologíaRESUMEN
Microstructural design was a long-term sustainable development method to improve the biodegradability and mechanical properties of low alloyed biomedical Mg alloys. In this study, the microstructural features (including grain size, deformation twin, deformed grains, sub-grains, and recrystallized grains) of the MZ2 ((Mg-2Zn (wt%)) alloy were controlled by different single-passed rolling reductions at high temperature. Besides the effect of grain size, we found that deformation twins and deformed grains influenced corrosion performance. Grain refinement with uniform distribution, meanwhile reducing the content of deformation twins, deformed grains, and sub-grains, was a practical method to improve both corrosion resistance and mechanical properties of MZ2 alloy. This finding proposed a better understanding of the development of lean biomedical Mg alloys with superior mechanical properties and favorable corrosion resistance. STATEMENT OF SIGNIFICANCE: Current research and development of biomedical Mg focused on alloying methods. The lean biodegradable Mg, which reduced the materials' compositional complexity, was the benefit of development for long-term sustainability. Here, our work revealed the relationship between microstructural features and corrosion resistance of a lean Mg-2Zn alloy during the different single-passed rolling processes. We found that recrystallized fine grains with partially ultra-fine grains could improve both strength and corrosion resistance. This study could give a new understanding of the development of lean biodegradable Mg alloys by using microstructural design to improve the overall performance of biomedical applications.
Asunto(s)
Aleaciones/química , Materiales Biocompatibles/química , Magnesio/química , Zinc/química , Aleaciones/toxicidad , Animales , Materiales Biocompatibles/toxicidad , Línea Celular , Calor , Magnesio/toxicidad , Ensayo de Materiales , Ratones , Oxidación-Reducción , Tamaño de la Partícula , Resistencia a la Tracción , Zinc/toxicidadRESUMEN
The common treatment of epithelial ovarian cancer is aggressive surgery followed by platinum-based cytotoxic chemotherapy. However, residual tumor cells are resistant to chemotherapeutic drugs during postoperative recurrence. The treatment of ovarian cancer requires breakthroughs and advances. In recent years, magnesium alloy has been widely developed as a new biodegradable material because of its great potential in the field of medical devices. From the degradation products of magnesium, biodegradable magnesium implants have great potential in antitumor. According to the disease characteristics of ovarian cancer, we choose it to study the antitumor characteristics of biodegradable magnesium. We tested the anti-ovarian tumor properties of Mg through both in vivo and in vitro experiments. According to the optical in vivo imaging and relative tumor volume statistics of mice, high-purity Mg wires significantly inhibited the growth of SKOV3 cells in vivo. We find that the degradation products of Mg, Mg2+, and H2 significantly inhibit the growth of SKOV3 cells and promote their apoptosis. Our study suggests a good promise for the treatment of ovarian cancer.
Asunto(s)
Recurrencia Local de Neoplasia , Neoplasias Ováricas , Implantes Absorbibles , Animales , Apoptosis , Carcinoma Epitelial de Ovario , Femenino , Humanos , Ratones , Neoplasias Ováricas/tratamiento farmacológicoRESUMEN
Mg-based implants are used in biomedical applications predominantly because of their degradable property. In this paper, the effect of local misorientations (intragranular misorientation) on the corrosion behavior of high-purity Mg (HPM) was systematically investigated according to microstructure characterization and corrosion measurements. The results showed that local misorientation introduced into grains by deformation could result in corrosion around the grain boundary (GB), which ultimately reduces the corrosion resistance of HPM. After removing the local misorientation by annealing, the corrosion around GB could be eliminated. This work is expected to inspire better control over the degradation behaviors of biomedical Mg through microstructure design to be used for various biomedical applications. STATEMENT OF SIGNIFICANCE: 1. Fine grains, fine grains with large local misorientation, and coarse grains could be obtained, respectively, in high-purity Mg by sequential hot rolling, compression deformation, and annealing treatments. 2. Large local misorientation introduced into grains could lead to corrosion around the grain boundary and ultimately reduce corrosion resistance. 3. In the absence of local misorientation, refining grain size could improve the corrosion resistance of Mg.
Asunto(s)
Materiales Biocompatibles/química , Magnesio/química , Corrosión , Espectroscopía Dieléctrica , Módulo de Elasticidad , DurezaRESUMEN
There is an increasing need to develop conducting hydrogels for bioelectronic applications. In particular, poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) hydrogels have become a research hotspot due to their excellent biocompatibility and stability. However, injectable PEDOT:PSS hydrogels have been rarely reported. Such syringe-injectable hydrogels are highly desirable for minimally invasive biomedical therapeutics. Here, an approach is demonstrated to develop injectable PEDOT:PSS hydrogels by taking advantage of the room-temperature gelation property of PEDOT:PSS. These PEDOT:PSS hydrogels form spontaneously after syringe injection of the PEDOT:PSS suspension into the desired location, without the need of any additional treatments. A facile strategy is also presented for large-scale production of injectable PEDOT:PSS hydrogel fibers at room temperature. Finally, it is demonstrated that these room-temperature-formed PEDOT:PSS hydrogels (RT-PEDOT:PSS hydrogel) and hydrogel fibers can be used for the development of soft and self-healable hydrogel bioelectronic devices.
Asunto(s)
Hidrogeles/química , Poliestirenos/química , Tiofenos/química , Animales , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Línea Celular , Proliferación Celular/efectos de los fármacos , Electrodos , Ratones , Células Musculares/citología , Células Musculares/metabolismo , Temperatura , Transistores ElectrónicosRESUMEN
A highly ordered TiO2 nanotube array has been prepared on a commercial pure titanium substrate in a hydrofluoric (HF) electrolyte using a DC power source through two-step anodic oxidation. The morphology, composition, wettability and surface energy of the nanotube array have been characterized by using a field-emission scanning electron microscope (FE-SEM), a transmission electron microscope (JEM-2010) with energy-dispersive X-ray spectrometer EDX (INCA OXFORD), X-ray diffraction method, an atomic force microscope (AFM), an optical contact angle measuring device and the Owens method with two liquids. The electrochemical behaviours of anodic oxidation films with different structures have been investigated in Sodium Lactate Ringer's Injection at 37±1°C by potentiodynamic polarization curve and electrochemical impedance spectroscopy. The formation mechanism of the nanotube array and the advantages of two-step oxidation have been discussed according to the experimental observation and the characterized results. Meanwhile, the structural changes of nanotubes are analysed according to the results of impedance spectroscopy. Cytotoxicity testing and cell adhesion and proliferation have been studied in order to evaluate the bioactivity of the nanotube array film. The diameters of nanotubes are in the range of 120-140 nm. The nanotube surface shows better wettability and higher surface energy compared to the bare substrate. The nanotube surface exhibits a wide passivation range and good corrosion resistance. The growth of the nanotube array is the result of the combined action of the anodization and field-assisted dissolution. The nanotube array by two-step oxidation becomes more regular and orderly. Moreover, the nanotube array surface is non-toxic and favourable to cell adhesion and proliferation. Such nanotube array films are expected to have significant biomedical applications.
RESUMEN
Crevice-induced corrosion is not desirable to occur in metallic magnesium (Mg) during many industrial applications. However, orthopedic implants made of Mg alloys have been demonstrated to degrade faster between the joining surface of bone plates and screws after implantation, suggesting the crevice corrosion may occur in the physiological environment. In this paper, a resin device is designed to parallel high purity magnesium (HP-Mg) plates with closely spaced slits. After a standard corrosion test in the phosphate-buffered saline (PBS) solution, the paralleled HP-Mg samples embedded in the custom-made resin device corrode faster than those without the resin device. The corrosion morphology of Mg with the resin device exhibits features of crevice corrosion with many deep holes and river-like texture. Moreover, implantation of the bone plate and screws in vivo demonstrates similar corrosion morphology as that of the in vitro test, suggesting the occurrence of crevice-enhanced corrosion in the bone-bone plate interface, as well as the contact area between the bone plate and the screws. STATEMENT OF SIGNIFICANCE: Understanding the corrosion behavior of Mg and Mg alloys after implantation is one of the main challenges for developing desirable biodegradable Mg alloys or effective methods to adjust the corrosion rate of Mg-based implants. In this paper, we attempted to understand the corrosion behaviors of HP-Mg at the joining surface between HP-Mg plates or HP-Mg screws and bone tissues after implantation. We designed an in vitro setup to mimic the crevice environment of the in vivo joining surface and found that the crevices existing on the HP-Mg would significantly accelerate the corrosion rate and change the corrosion morphology of HP-Mg plates. The in vivo implantation also showed similar corrosion morphology caused by crevice corrosion, which appeared at the joining surface between HP-Mg plates or HP-Mg screws and bone tissues. Then, we proposed a new corrosion mechanism of Mg-based alloys inside the crevice. The findings of this study can help us broaden our cognition on the corrosion behavior of Mg and Mg alloy-based orthopedic implants.