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Smart dressings integrated with bioelectronics have attracted considerable attention and become promising solutions for skin wound management. However, due to the mechanical distinction between human body and the interface of electronics, previous smart dressings often suffered obvious degradation in electrical performance when attached to the soft and curvilinear wound sites. Here, we report a stretchable dressing integrated with temperature and pH sensor for wound status monitoring, as well as an electrically controlled drug delivery system for infection treatment. The wound dressing was featured with the deployment of liquid metal for seamless connection between rigid electrical components and gold particle-based electrodes, achieving a stretchable soft-hard interface. Stretching tests showed that both the sensing system and drug delivery system exhibited good stretchability and long-term stable conductivity with the resistance change rate less than 6 % under 50 % strain. Animal experiments demonstrated that the smart dressing was capable of detecting bacterial infection via the biomarkers of temperature and pH value and the infection factors of wound were significantly improved with therapy through electrically controlled antibiotics releasing. This proof-of-concept prototype has potential to significantly improve management of the wound, especially those with dynamic strain.
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Cesium lead halide (CsPbX3, X = Br, Cl, and I) nanocrystals (NCs) are widely concerned and applied in many fields due to the excellent photoelectric performance. However, the toxicity of Pb and the loss of luminescence in water limit its application in vivo. A stable perovskite nanomaterial with good bioimaging properties is developed by incorporating europium (Eu) in CsPbX3 NCs followed with the surface coating of silica (SiO2) shell (CsPbX3:Eu@SiO2). Through the surface coating of SiO2, the luminescence stability of CsPbBr3 in water is improved and the leakage of Pb2+ is significantly reduced. In particular, Eu doping inhibits the photoluminescence quantum yield reduction of CsPbBr3 caused by SiO2 coating, and further reduces the release of Pb2+. CsPbBr3:Eu@SiO2 nanoparticles (NPs) show efficient luminescence in water and good biocompatibility to achieve cell imaging. More importantly, CsPb(ClBr)3:Eu@SiO2 NPs are obtained by adjusting the halogen components, and green light and blue light are realized in zebrafish imaging, showing good imaging effect and biosafety. The work provides a strategy for advanced perovskite nanomaterials toward biological practical application.
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Césio , Európio , Chumbo , Luminescência , Nanopartículas , Dióxido de Silício , Água , Peixe-Zebra , Animais , Dióxido de Silício/química , Európio/química , Nanopartículas/química , Chumbo/química , Césio/química , Água/química , Titânio/química , Óxidos , Compostos de CálcioRESUMO
Disease or organ damage due to unhealthy living habits, or accidents, is inevitable. Discovering an efficient strategy to address these problems is urgently needed in the clinic. In recent years, the biological applications of nanotechnology have received extensive attention. Among them, as a widely used rare earth oxide, cerium oxide (CeO2 ) has shown good application prospects in biomedical fields due to its attractive physical and chemical properties. Here, the enzyme-like mechanism of CeO2 is elucidated, and the latest research progress in the biomedical field is reviewed. At the nanoscale, Ce ions in CeO2 can be reversibly converted between +3 and +4. The conversion process is accompanied by the generation and elimination of oxygen vacancies, which give CeO2 the performance of dual redox properties. This property facilitates nano-CeO2 to catalyze the scavenging of excess free radicals in organisms, hence providing a possibility for the treatment of oxidative stress diseases such as diabetic foot, arthritis, degenerative neurological diseases, and cancer. In addition, relying on its excellent catalytic properties, customizable life-signaling factor detectors based on electrochemical techniques are developed. At the end of this review, an outlook on the opportunities and challenges of CeO2 in various fields is provided.
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Cério , Nanopartículas , Medicina de Precisão , Estresse Oxidativo , Cério/química , Antioxidantes , Nanopartículas/químicaRESUMO
Osteosarcoma occurs in children and adolescents frequently and leads to a high fatality rate. Although surgical resection is the most common methods in clinic, patients always suffer from tumor metastasis and recurrence and it is difficult for them to self-repair large bone defects. Furthermore, the postoperative infection from bacteria triggers an inflammatory response and hinders the bone-repair process. This work demonstrates a gadolinium (Gd)-complex and molybdenum sulfide (MoS2 ) co-doped N-acryloyl glycinamide (NAGA)/gelatin methacrylate (Gel-MA) multifunctional hydrogel (GMNG). The combination between NAGA and Gel-MA endows the GMNG with attractive mechanical properties and controllable degradation ability. The MoS2 improves the hydrogel system, which has excellent photothermal ability to kill tumor cells and inhibit bacterial infection both in vitro and in vivo. Based on the Gd-complex, the magnetic resonance imaging (MRI) effect can be used to monitor the position and degradation situation of the hydrogel. Notably, accompanied by the degradation of GMNG hydrogel, the gradually released Gd3+ from the hydrogel exhibits osteogenic property and could promote new bone formation efficiently in vivo. Therefore, this strategy supplies a method to prepare multifunctional bone-defect-repair materials and is expected to represent a significant guidance and reference to the development of biomaterials for bone tissue engineering.
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Neoplasias Ósseas , Engenharia Tecidual , Criança , Humanos , Adolescente , Molibdênio , Recidiva Local de Neoplasia , Regeneração Óssea , Alicerces Teciduais , Osteogênese , Remodelação Óssea , Hidrogéis , Neoplasias Ósseas/terapiaRESUMO
Rational design of multifunctional biomaterials with customized architecture and on demand bioactivity is of great significance for bone tissue engineering (BTE) in modern society. Herein, a versatile therapeutic platform has been established by integrating cerium oxide nanoparticles (CeO2 NPs) into bioactive glass (BG) to fabricate three-dimensional (3D)-printed scaffolds, achieving a sequential therapeutic effect against inflammation and promoting osteogenesis toward bone defect. The antioxidative activity of CeO2 NPs plays a crucial role in alleviating the oxidative stress upon formation of bone defects. Subsequently, CeO2 NPs exert a promotion effect on the proliferation and osteogenic differentiation of rat osteoblasts through enhancing mineral deposition and alkaline phosphatase and osteogenic gene expression. Strikingly, the incorporation of CeO2 NPs bestows on the BG scaffolds greatly reinforced mechanical properties, improved biocompatibility, adequate cell adhesion, elevated osteogenic capability, and multifunctional performance in a single platform. In vivo studies on the treatment of rat tibial defect confirmed the better osteogenic properties of CeO2-BG scaffolds compared with pure BG scaffolds. Additionally, the employment of the 3D printing technique creates a proper porous microenvironment around the bone defect, which further facilitates the cell in-growth and new bone formation. This report provides a systematic study on CeO2-BG 3D-printed scaffolds prepared by simple ball milling method, achieving sequential and integral treatment in BTE based on a single platform.
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Osteogênese , Alicerces Teciduais , Ratos , Animais , Regeneração Óssea , Engenharia Tecidual/métodos , Vidro , Impressão TridimensionalRESUMO
Cesium lead halide (CsPbX3, X = Br, Cl, I) perovskite nanocrystals (NCs) possess tunable band gaps across the entire visible spectral range and are promising for various optoelectronic device applications. However, poor performance in adverse conditions limits their further development in practical optoelectronics. Herein, highly stable perovskite NCs are developed by doping europium(II) (Eu2+) into the B-site of CsPbBr3 with negligible lattice distortion/strain. Eu2+-doped CsPbBr3 NCs exhibit tunable green-to-cyan emissions, high photoluminescence quantum yield, and good resistance to harsh conditions, including ultraviolet irradiation, erosion of moisture, and corrosion of polar solvent molecules. In particular, the thermal stability of CsPbBr3 NCs after Eu2+ doping is greatly enhanced under continuous heating in air, while exhibiting the emissions of Eu2+. Furthermore, a Eu2+-doped CsPbBr3 NC-based cyan light-emitting diode is fabricated, which exhibits narrow exciton emission driven under different current densities. This work would open the avenue to develop the rational lanthanide ion doping strategy for further advancing perovskite nanomaterials toward practical applications.
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CoF2, with a relatively high theoretical capacity (553 mA h g-1), has been attracting increasing attention in the energy storage field. However, a facile and controllable synthesis of monodispersed CoF2 and CoF2-based nano-heterostructures have been rarely reported. In this direction, an eco-friendly and precisely controlled colloidal synthesis strategy to grow uniformly sized CoF2 nanorods and LiF-tipped CoF2-nanorod heterostructures based on a seeded-growth method is established. The unveiled selective growth of LiF nanoparticles onto the two end tips of the CoF2 nanorods is associated with the higher energy of tips, which favors the nucleation of LiF nanocrystals. Notably, it was found that LiF could protect CoF2 from corrosion even after 9 months of aging. In addition, the as-obtained heterostructures were employed in supercapacitors and lithium sulfur batteries as cathode materials. The heterostructures consistently exhibited higher specific capacities than the corresponding two single components in both types of energy storage devices, making it a potential electrode material for energy storage applications.
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Wound infection is a common clinical problem. Traditional detection methods can not provide infection early warning information in time. With the development of flexible electronics, flexible wearable devices have been widely used in the field of intelligent monitoring. Here, we describe the development of a soft wound infection monitoring system with pH sensors and temperature sensors. The measurement range of pH was 4-10, the fitting accuracy was 99.8%, and the response time was less than 6 s. The temperature sensor array showed good accuracy and short response times in the range of 30 °C to 40 °C. A series of in vitro tests and the use of a rat model of Staphylococcus aureus infection confirmed that this flexible detection system can monitor the pH and temperature changes occurring in the early stage of infection, which provides an effective reference for clinical application.
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Reducing the inflammatory response is a major goal in the therapy of rheumatoid arthritis (RA). Herein, we integrated palladium nanoparticles (Pd NPs) with selenium nanoparticles (Se NPs) and obtained a multiple nanosystem (Pd@Se-HA NPs) that could simultaneously scavenge hydroxyl radicals (â OH) and provide a photothermal effect. The Pd@Se-HA NPs were constructed by a simple self-assembly method in which Se NPs were electrostatically bonded to Pd NPs; hyaluronic acid (HA) was linked to the NPs by ester bonding to provide macrophage targeting ability. The experiments show that the combined therapy of eliminating â OH with Se NPs and utilizing PTT with Pd NPs could effectively reduce the inflammatory response in macrophages more effectively than either individual NP treatment. In addition, the outer layer of HA could specifically target the CD44 receptor to enhance the accumulation of Pd@Se NPs at the lesion, further enhancing the therapeutic effect. After treatment for 15 days, the Pd@Se-HA NPs nearly eliminated the inflammatory response in the joints of mice in an induced RA model, and prevented joint damage and degradation.
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Chronic wounds, such as the diabetic ulcer wounds have serious effect on people's lives, and can even lead to death. Diabetic ulcer wounds are different from normal wounds and much easier to be infected and induce oxidative stress due to the special surrounding microenvironment, which makes it necessary to prepare materials with antibacterial property and antioxidant activity simultaneously. The molybdenum disulfide-ceria (MoS2 -CeO2 ) nanocomposite possesses both the photo-thermal therapy (PTT) antibacterial capability of polyethylene glycol modified molybdenum disulfide nanosheets and the antioxidant activity of cerium dioxide nanoparticles (CeO2 NPs). By combining the inherent antibacterial activity of CeO2 NPs, the MoS2 -CeO2 nanocomposite exhibits excellent PTT antibacterial capability against both gram-positive and gram-negative bacteria through 808 nm laser treatment, thereby reducing the risk of wound infection. Owing to the abundant oxygen vacancies in CeO2 NPs, Ce3+ and Ce4+ can transform reversibly which endows MoS2 -CeO2 nanocomposite with remarkable antioxidant ability to clear away the excessive reactive oxygen species around the diabetic ulcer wounds and promote wound healing. The results demonstrate that MoS2 -CeO2 nanocomposite is a promising class for the clinical treatment of chronic wounds especially the diabetic ulcer wounds, and 808 nm laser can be used as a PTT antibacterial switch.
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Antibacterianos , Antioxidantes , Antibacterianos/farmacologia , Antioxidantes/farmacologia , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Humanos , CicatrizaçãoRESUMO
Although clay-based nanocomposite hydrogels have been widely explored, their instability in hot water and saline solution inhibits their applications in biomedical engineering, and the exploration of clay-based nanocomposite hydrogels in bone defect repair is even less. In this work, we developed a stable clay-based nanocomposite hydrogel using 4-acryloylmorpholine as the monomer. After UV light illumination, the obtained poly(4-acryloylmorpholine) clay-based nanocomposite hydrogel (poly(4-acry)-clay nanocomposite hydrogel) exhibits excellent mechanical properties due to the hydrogen bond interactions between the poly(4-acryloylmorpholine) chains and the physical crosslinking effect of the nanoclay. Besides good biocompatibility, the sustainable release of intrinsic Mg2+ and Si4+ from the poly(4-acry)-clay nanocomposite hydrogel endows the system with excellent ability to promote the osteogenic differentiation of primary rat osteoblasts (ROBs) and can promote new bone formation effectively after implantation. We anticipate that these kinds of clay-based nanocomposite hydrogels with sustained release of bioactive ions will open a new avenue for the development of novel biomaterials for bone regeneration.
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Osso e Ossos/efeitos dos fármacos , Argila/química , Hidrogéis/química , Hidrogéis/farmacologia , Fenômenos Mecânicos , Nanocompostos/química , Acrilamidas/química , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Regeneração Óssea/efeitos dos fármacos , Osso e Ossos/citologia , Osso e Ossos/fisiologia , Diferenciação Celular/efeitos dos fármacos , Morfolinas/química , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , RatosRESUMO
The fate of cells and subsequent bone regeneration is highly correlated with temporospatial coordination of chemical, biological, or physical cues within a local tissue microenvironment. Deeper understanding of how mammalian cells react to local tissue microenvironment is paramount important when designing next generation of biomaterials for tissue engineering. This study aims to investigate that the regulation of magnesium cationic (Mg2+) tissue microenvironment is able to convince early-stage bone regeneration and its mechanism undergoes intramembranous ossification. It was discovered that moderate Mg2+ content niche (~4.11 mM) led to superior bone regeneration, while Mg2+-free and strong Mg2+ content (~16.44 mM) discouraged cell adhesion, proliferation and osteogenic differentiation, thereby bone formation was rarely found. When magnesium ions diffused into free Mg zone from concentrated zone in late time point, new bone formation on free Mg zone became significant through intramembranous ossification. This study successfully demonstrates that magnesium cationic microenvironment serves as an effective biochemical cue and is able to modulate the process of bony tissue regeneration. The knowledge of how a Mg2+ cationic microenvironment intertwines with cells and subsequent bone formation gained from this study may provide a new insight to develop the next generation of tissue-repairing biomaterials.
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Rare earth (RE) elements are widely used in the luminescence and magnetic fields by virtue of their abundant 4f electron configurations. However, the overall performance and aqueous stability of single-component RE materials need to be urgently improved to satisfy the requirements for multifunctional applications. Carbon nanodots (CNDs) are excellent nanocarriers with abundant functional surface groups, excellent hydrophilicity, unique photoluminescence (PL) and tunable features. Accordingly, RE-CND hybrids combine the merits of both RE and CNDs, which dramatically enhance their overall properties such as luminescent and magnetic-optical imaging performances, leading to highly promising practical applications in the future. Nevertheless, a comprehensive review focusing on the introduction and in-depth understanding of RE-CND hybrid materials has not been reported to date. This review endeavors to summarize the recent advances of RE-CNDs, including their interaction mechanisms, general synthetic strategies and applications in fluorescence, biosensing and multi-modal biomedical imaging. Finally, we present the current challenges and the possible application perspectives of newly developed RE-CND materials. We hope this review will inspire new design ideas and valuable references in this promising field in the future.
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Carbono/química , Meios de Contraste/química , Complexos de Coordenação/química , Corantes Fluorescentes/química , Metais Terras Raras/química , Pontos Quânticos/química , Animais , Técnicas Biossensoriais , Transferência Ressonante de Energia de Fluorescência , Humanos , Imageamento por Ressonância Magnética , Imagem Óptica , Propriedades de Superfície , Nanomedicina TeranósticaRESUMO
Wound dressings based on injectable thermo-sensitive hydrogel possess several advantages over preformed conventional dressings such as rapid reversible sol-gel transition behavior and the capacity of filling the irregular wound defect. Nevertheless, its clinical application is hindered by the weak tissue adhesiveness. Therefore, in this study, the catechol modified quaternized chitosan (QCS-C) was fabricated and incorporated into poly(d,l-lactide)-poly(ethylene glycol)-poly(d,l-lactide) (PLEL) hydrogel to develop an injectable hydrogel with the properties of thermo-sensitive, antibacterial and tissue adhesive. QCS-C could lower the LCST of hydrogel for easy gelation at physiological temperature, and significantly enhanced the tissue adhesion. For wound generation, nano-scaled bioactive glass (nBGï¼80 SiO2, 16 CaO and 4 P2O5; mol%) was loaded into hydrogel to promote angiogenesis. The mice partial laceration experiment showed that PLEL-nBG-QCS-C hydrogel could effectively seal the ruptured skin and significantly accelerate wound healing. Thus, our findings established a new type of clinical treatment technology for complicated wounds.
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Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Catecóis/química , Quitosana/química , Hidrogéis/administração & dosagem , Lacerações/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Adesivos/química , Adesivos/farmacologia , Animais , Antibacterianos/química , Apoptose , Bandagens , Materiais Biocompatíveis/química , Proliferação de Células , Células Cultivadas , Liberação Controlada de Fármacos , Fibroblastos/efeitos dos fármacos , Humanos , Hidrogéis/química , Masculino , Camundongos , Camundongos Endogâmicos BALB C , TemperaturaRESUMO
It is generally accepted that biodegradable materials greatly influence the nearby microenvironment where cells reside; however, the range of interfacial properties has seldom been discussed due to technical bottlenecks. This study aims to depict biomaterial microenvironment boundaries by correlating interfacial H+ distribution with surrounding cell behaviors. Using a disuse-related osteoporotic mouse model, we confirmed that the abnormal activated osteoclasts could be suppressed under relatively alkaline conditions. The differentiation and apatite-resorption capability of osteoclasts were "switched off" when cultured in titrated material extracts with pH values higher than 7.8. To generate a localized alkaline microenvironment, a series of borosilicates were fabricated and their interfacial H+ distributions were monitored spatiotemporally by employing noninvasive microtest technology. By correlating interfacial H+ distribution with osteoclast "switch on/off" behavior, the microenvironment boundary of the tested material was found to be 400 ± 50 µm, which is broader than the generally accepted value, 300 µm. Furthermore, osteoporotic mice implanted with materials with higher interfacial pH values and boarder effective ranges had lower osteoclast activities and a thicker new bone. To conclude, effective proton microenvironment boundaries of degradable biomaterials were depicted and a weak alkaline microenvironment was shown to promote regeneration of osteoporotic bones possibly by suppressing abnormal activated osteoclasts.
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Materiais Biocompatíveis/química , Regeneração Óssea , Meios de Cultura/química , Animais , Materiais Biocompatíveis/farmacologia , Doenças Ósseas/metabolismo , Doenças Ósseas/patologia , Regeneração Óssea/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Modelos Animais de Doenças , Durapatita/química , Feminino , Concentração de Íons de Hidrogênio , Masculino , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Osteoclastos/citologia , Osteoclastos/metabolismo , Osteogênese/efeitos dos fármacos , Células RAW 264.7 , Ratos , Ratos Sprague-DawleyRESUMO
Synthetic biodegradable polymeric scaffolds with uniformly interconnected pore structure, appropriate mechanical properties, excellent biocompatibility, and even enhanced osteogenesis ability are urgently required for in situ bone regeneration. In this study, for the first time, a series of biodegradable piperazine (PP)-based polyurethane-urea (P-PUU) scaffolds with a gradient of PP contents were developed by air-driven extrusion 3D printing technology. The P-PUU ink of 60 wt % concentration was demonstrated to have appropriate viscosity for scaffold fabrication. The 3D-printed P-PUU scaffolds exhibited an interconnected porous structure of about 450 µm in macropore size and about 75% in porosity. By regulating the contents of PP in P-PUU scaffolds, their mechanical properties could be moderated, and P-PUU1.4 scaffolds with the highest PP contents exhibited the highest compressive modulus (155.9 ± 5.7 MPa) and strength (14.8 ± 1.1 MPa). Moreover, both in vitro and in vivo biological results suggested that the 3D-printed P-PUU scaffolds possessed excellent biocompatibility and osteoconductivity to facilitate new bone formation. The small molecular PP itself was confirmed for the first time to regulate osteogenesis of osteoblasts in a dose-dependent manner and the optimum concentration for osteoconductivity was about â¼0.5 mM, which suggests that PP molecules, together with the mechanical behavior, nitrogen-contents, and hydrophilicity of P-PUUs, play an important role in enhancing the osteoconductive ability of P-PUU scaffolds. Therefore, the 3D-printed P-PUU scaffolds, with suitable interconnected pore structure, appropriate mechanical properties, and intrinsically osteoconductive ability, should provide a promising alternative for bone regeneration.
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Materiais Biocompatíveis/química , Piperazina/química , Poliuretanos/química , Alicerces Teciduais/química , Animais , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/uso terapêutico , Doenças Ósseas/terapia , Doenças Ósseas/veterinária , Regeneração Óssea/efeitos dos fármacos , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Força Compressiva , Camundongos , Osteoblastos/citologia , Osteoblastos/metabolismo , Osteogênese/efeitos dos fármacos , Porosidade , Impressão Tridimensional , Ratos , Engenharia TecidualRESUMO
An osteoblast-laden nanocomposite hydrogel construct, based on polyethylene glycol diacrylate (PEGDA)/laponite XLG nanoclay ([Mg5.34Li0.66Si8O20(OH)4]Na0.66, clay)/hyaluronic acid sodium salt (HA) bio-inks, is developed by a two-channel 3D bioprinting method. The novel biodegradable bio-ink A, comprised of a poly(ethylene glycol) (PEG)-clay nanocomposite crosslinked hydrogel, is used to facilitate 3D-bioprinting and enables the efficient delivery of oxygen and nutrients to growing cells. HA with encapsulated primary rat osteoblasts (ROBs) is applied as bio-ink B with a view to improving cell viability, distribution uniformity, and deposition efficiency. The cell-laden PEG-clay constructs not only encapsulated osteoblasts with more than 95% viability in the short term but also exhibited excellent osteogenic ability in the long term, due to the release of bioactive ions (magnesium ions, Mg2+ and silicon ions, Si4+), which induces the suitable microenvironment to promote the differentiation of the loaded exogenous ROBs, both in vitro and in vivo. This 3D-bioprinting method holds much promise for bone tissue regeneration in terms of cell engraftment, survival, and ultimately long-term function.
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In this work, a biodegradable and biocompatible nanocomposite hydrogel was successfully prepared on basis of nanoclay and polyethylene-glycol diacrylates (PEGDA). The physical interspersing between nanoclay particles and PEG chains combined with the chemical crosslinking within the PEG networks endowed the obtained nanocomposite hydrogels with enhanced mechanical properties in comparison with pure PEG hydrogels. Simultaneously, the incorporation of nanoclay to the PEGDA/nanoclay (PEGDA-Clay) nanocomposite hydrogel not only improved the adsorption and spreading ability of cells on the hydrogels, but also effectively facilitated the in vitro osteogenic differentiation of primary rat osteoblasts due to the sustainable release of magnesium ions (Mg2+) and silicon ions (Si4+) from the PEGDA-Clay nanocomposite hydrogel. In addition, the implantation of the PEGDA-Clay nanocomposite hydrogels in the tibia defects of Sprague-Dawley rat could promoted the new bone formation efficiently, further suggesting the excellent osteogenic ability of PEGDA-Clay nanocomposite hydrogel. We expect that this kind of biocompatible nanocomposite hydrogels with attractive mechanical properties and a variety of bioactive osteogenic ions will offer a new possibility for bone tissue regeneration.
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Nanocompostos , Osteogênese , Animais , Hidrogéis , Polietilenoglicóis , Polietilenos , Ratos , Ratos Sprague-DawleyRESUMO
Uncontrolled hemorrhage is the main cause of death in many situations. Substantial efforts have been focused on developing more efficient hemostatic agents. Meanwhile, their safety is also critical for their application. Chitosan is an attractive natural polymer and has been widely investigated for hemostatic application. This study sought to incorporate poly(vinyl alcohol) (PVA) components and fabricate them into monodisperse millimeter-sized spheres to improve efficiency and safety. Chitosan-PVA spheres were fabricated by electrospraying and ionotropic gelation. The millimeter-sized spheres were obtained by adjusting the electrospraying parameters, including applied voltage, working distance, feed rate, polymer solution and component content. The morphology, chemical structure and thermostability of the spheres were characterized by variable pressure scanning electron microscopy (VP-SEM), Fourier transform infrared (FTIR) spectroscopy and thermogravimetric analysis (TGA). These spheres showed narrow size distribution and good biocompatibility. The hemostatic effect was evaluated both in vitro and in vivo using a blood coagulation timing experiment and a rat liver hemorrhaging model, and chitosan50-PVA50 spheres showed the best effect. PVA contributed to the high swelling degree of the spheres and the enhanced hemostatic effect. These spheres also significantly reduced thromboembolus formation in controlling femoral artery bleeding compared with chitosan powder, providing an efficient and safe hemostasis agent.
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The emerging 3D bioprinting technique that is strongly dependent on the development of bioinks offers a promising opportunity to customize personalized bioscaffolds for precision and individualized therapy of bone defects. Hydrogels are one sort of attractive scaffolding materials due to their resemblance to extracellular matrices. Although much progress has been made in designing and fabricating high strength hydrogels, very few of them have been extended to the treatment of bone defects. In this work, we developed a hybrid bioink composed of a hydrogen bonding monomer (N-acryloyl glycinamide) (NAGA) and nanoclay. The hybrid ink could be conveniently tailored as a high strength PNAGA-Clay composite scaffold under UV light illumination of printed prehydrogel. The hydrogen bonding combined with physical cross-linking of nanoclay contributed to the superior mechanical performances as well as swelling stability of the hydrogels and bioscaffols. The sustainable release of intrinsic Mg2+ and Si4+ from the PNAGA-Clay scaffold was shown to promote the osteogenic differentiation of primary rat osteoblast (ROB) cells. Importantly, this implantable PNAGA-Clay scaffold highly efficiently facilitated the regeneration of new bone in tibia defects of rats. We anticipate that hybridization of the hydrogen bonding monomer with a variety of bioactive inorganic nanoparticles will offer new possibilities to develop numerous bioinks for 3D-printing of desired bioscaffolds to realize individualized repair of degenerated load-bearing tissues.