ABSTRACT
Portal vein tumor thrombus (PVTT) formed by cancer cell invasion is a major cause of high mortality in hepatocellular carcinoma (HCC), and the formation of thrombus will be accelerated by bacterial colonization on the surface of the implant after surgery. In this work, Polypyrrole-coated arsenic-loaded layered double hydroxide films were in situ constructed on the nickel-titanium alloy for the efficient killing of tumour cells by thermo-therapeutic synergistic chemotherapy. The good near-infrared photothermal conversion ability of polypyrrole enables the sample surface temperature to be raised to about 51 °C at a low photothermal power (0.5 w/cm2), while the elevated temperature could further accelerate the release of drug arsenic. In addition, when NIR light is not applied, the polypyrrole coating also cleverly acts as a "barrier layer" to reduce the natural release of arsenic in normal tissues to avoid toxicity issues. In vivo and in vitro experiments have demonstrated that the platform exhibits excellent antitumor and antibacterial abilities. In contrast to the systemic toxicity issues associated with systemic circulation of nanotherapeutic drugs, this in situ functional film is expected to be used in localised interventions for precise drug delivery, and is also more suitable for surgical treatment scenarios in PVTT surgeries.
ABSTRACT
Nickel-titanium alloy stents are widely used in the interventional treatment of various malignant tumors, and it is important to develop nickel-titanium alloy stents with selective cancer-inhibiting and antibacterial functions to avoid malignant obstruction caused by tumor invasion and bacterial colonization. In this work, an acid-responsive layered double hydroxide (LDH) film was constructed on the surface of a nickel-titanium alloy by hydrothermal treatment. The release of nickel ions from the film in the acidic tumor microenvironment induces an intracellular oxidative stress response that leads to cell death. In addition, the specific surface area of LDH nanosheets could be further regulated by heat treatment to modulate the release of nickel ions in the acidic microenvironment, allowing the antitumor effect to be further enhanced. This acid-responsive LDH film also shows a good antibacterial effect against S. aureus and E. coli. Besides, the LDH film prepared without the introduction of additional elements maintains low toxicity to normal cells in a normal physiological environment. This work offers some guidance for the design of a practical nickel-titanium alloy stent for the interventional treatment of tumors.
Subject(s)
Anti-Bacterial Agents , Hydroxides , Nickel , Tumor Microenvironment , Hydroxides/chemistry , Hydroxides/pharmacology , Tumor Microenvironment/drug effects , Nickel/chemistry , Nickel/pharmacology , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Alloys/chemistry , Alloys/pharmacology , Escherichia coli/drug effects , Staphylococcus aureus/drug effects , Titanium/chemistry , Titanium/pharmacology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Hydrogen-Ion ConcentrationABSTRACT
Infection and poor tissue repair are the key causes of percutaneous implantation failure. However, there is a lack of effective strategies to cope with due to its high requirements of sterilization, soft tissue healing, and osseointegration. In this work, l-arginine (L-Arg) was loaded onto a sulfonated polyetheretherketone (PEEK) surface to solve this issue. Under the infection condition, nitric oxide (NO) and reactive oxygen species (ROS) are produced through catalyzing L-Arg by inducible nitric oxide synthase (iNOS) and thus play a role in bacteria sterilization. Under the tissue repair condition, L-Arg is catalyzed to ornithine by Arginase-1 (Arg-1), which promotes the proliferation and collagen secretion of L929 and rBMSCs. Notably, L-Arg loading samples could polarize macrophages to M1 and M2 in infection and tissue repair conditions, respectively. The results in vivo show that the L-Arg loading samples could enhance infected soft tissue sealing and bone regeneration. In summary, L-Arg loading sulfonated PEEK could polarize macrophage through metabolic reprogramming, providing multi-functions of antibacterial abilities, soft tissue repair, and bone regeneration, which gives a new idea to design percutaneous implantation materials.
ABSTRACT
Transcutaneous implants that penetrate through skin or mucosa are susceptible to bacteria invasion and lack proper soft tissue sealing. Traditional antibacterial strategies primarily focus on bacterial eradication, but excessive exposure to bactericidal agents can induce noticeable tissue damage. Herein, a rechargeable model (HPI-Ti) was constructed using perylene polyimide, an aqueous battery material, achieving temporal-sequence regulation of bacterial killing and soft tissue sealing. Charge storage within HPI-Ti is achieved after galvanostatic charge, and chemical discharge is initiated when immersed in physiological environments. During the early discharge stage, post-charging HPI-Ti demonstrates an antibacterial rate of 99.96 ± 0.01 % for 24 h, preventing biofilm formation. Contact-dependent violent electron transfer between bacteria and the material causes bacteria death. In the later discharge stage, the attenuated discharging status creates a gentler electron-transfer micro-environment for fibroblast proliferation. After discharge, the antibacterial activity can be reinstated by recharge against potential reinfection. The antibacterial efficacy and soft tissue compatibility were verified in vivo. These results demonstrate the potential of the charge-transfer-based model in reconciling antibacterial efficacy with tissue compatibility.
ABSTRACT
Implant-related secondary infections are a challenging clinical problem. Sonodynamic therapy (SDT) strategies are promising for secondary biofilm infections by nonsurgical therapy. However, the inefficiency of SDT in existing acoustic sensitization systems limits its application. Therefore, we take inspiration from popular metamaterials and propose the design idea of a metainterface heterostructure to improve SDT efficiency. The metainterfacial heterostructure is defined as a periodic arrangement of heterointerface monoclonal cells that amplify the intrinsic properties of the heterointerface. Herein, we develop a TiO2/Ti2O3/vertical graphene metainterface heterostructure film on titanium implants. This metainterface heterostructure exhibits extraordinary sonodynamic and acoustic-to-thermal conversion effects under low-intensity ultrasound. The modulation mechanisms of the metainterface for electron accumulation and separation are revealed. The synergistic sonodynamic/mild sonothermal therapy disrupts biofilm infections (antibacterial rates: 99.99% for Staphylococcus aureus, 99.54% for Escherichia coli), and the osseointegration ability of implants is significantly improved in in vivo tests. Such a metainterface heterostructure film lays the foundation for the metainterface of manipulating electron transport to enhance the catalytic performance and holding promise for addressing secondary biofilm infections.
Subject(s)
Anti-Bacterial Agents , Biofilms , Escherichia coli , Staphylococcus aureus , Titanium , Ultrasonic Therapy , Biofilms/drug effects , Titanium/chemistry , Titanium/pharmacology , Staphylococcus aureus/drug effects , Staphylococcus aureus/physiology , Escherichia coli/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Graphite/chemistry , Graphite/pharmacology , Mice , Animals , Microbial Sensitivity TestsABSTRACT
The limitations of solvent residues, unmanageable film growth regions, and substandard performance impede the extensive utilization of metal-organic framework (MOF) films for biosensing devices. Here, we report a strategy for ion design in gas-phase synthesized flexible MOF porous film to attain universal regulation of biosensing performances. The key fabrication process involves atomic layer deposition of induced layer coupled with lithography-assisted patterning and area-selective gas-phase synthesis of MOF film within a chemical vapor deposition system. Sensing platforms are subsequently formed to achieve specific detection of H2O2, dopamine, and glucose molecules by respectively implanting Co, Fe, and Ni ions into the network structure of MOF films. Furthermore, we showcase a practical device constructed from Co ions-implanted ZIF-4 film to accomplish real-time surveillance of H2O2 concentration at mouse wound. This study specifically elucidates the electronic structure and coordination mode of ion design in MOF film, and the obtained knowledge aids in tuning the electrochemical property of MOF film for advantageous sensing devices.
Subject(s)
Biosensing Techniques , Dopamine , Electrochemical Techniques , Hydrogen Peroxide , Metal-Organic Frameworks , Biosensing Techniques/methods , Metal-Organic Frameworks/chemistry , Hydrogen Peroxide/analysis , Hydrogen Peroxide/chemistry , Electrochemical Techniques/methods , Animals , Mice , Dopamine/analysis , Dopamine/chemistry , Glucose/analysis , Glucose/isolation & purification , Glucose/chemistry , Cobalt/chemistry , Nickel/chemistry , Ions/chemistryABSTRACT
Uveal melanoma (UM) is a leading intraocular malignancy with a high 5-year mortality rate, and radiotherapy is the primary approach for UM treatment. However, the elevated lactic acid, deficiency in ROS, and hypoxic tumor microenvironment have severely reduced the radiotherapy outcomes. Hence, this study devised a novel CoMnFe-layered double oxides (LDO) nanosheet with multienzyme activities for UM radiotherapy enhancement. On one hand, LDO nanozyme can catalyze hydrogen peroxide (H2O2) in the tumor microenvironment into oxygen and reactive oxygen species (ROS), significantly boosting ROS production during radiotherapy. Simultaneously, LDO efficiently scavenged lactic acid, thereby impeding the DNA and protein repair in tumor cells to synergistically enhance the effect of radiotherapy. Moreover, density functional theory (DFT) calculations decoded the transformation pathway from lactic to pyruvic acid, elucidating a previously unexplored facet of nanozyme activity. The introduction of this innovative nanomaterial paves the way for a novel, targeted, and highly effective therapeutic approach, offering new avenues for the management of UM and other cancer types.
Subject(s)
Lactic Acid , Melanoma , Reactive Oxygen Species , Tumor Microenvironment , Reactive Oxygen Species/metabolism , Humans , Lactic Acid/metabolism , Melanoma/metabolism , Melanoma/radiotherapy , Tumor Microenvironment/drug effects , Uveal Neoplasms/metabolism , Uveal Neoplasms/radiotherapy , Uveal Neoplasms/genetics , Cell Line, Tumor , Nanostructures/therapeutic use , Mice , Animals , Disease Models, AnimalABSTRACT
Achieving bacterial killing and osteogenic formation on an implant surface rarely occurs. In this study, a novel surface design-a palladium hydride (PdHx) film that enables these two distinct features to coexist is introduced. The PdHx lattice captures protons in the extracellular microenvironment of bacteria, disrupting their normal metabolic activities, such as ATP synthesis, nutrient co-transport, and oxidative stress. This disruption leads to significant bacterial death, as evidenced by RNA sequence analysis. Additionally, the unique enzymatic activity and hydrogen-loading properties of PdHx activate the human antioxidant system, resulting in the rapid clearance of reactive oxygen species. This process reshapes the osteogenic immune microenvironment, promoting accelerated osteogenesis. These findings reveal that the downregulation of the NOD-like receptor signaling pathway is critical for activating immune cells toward M2 phenotype polarization. This novel surface design provides new strategies for modifying implant coatings to simultaneously prevent bacterial infection, reduce inflammation, and enhance tissue regeneration, making it a noteworthy contribution to the field of advanced materials.
Subject(s)
Antioxidants , Osteogenesis , Palladium , Surface Properties , Palladium/chemistry , Osteogenesis/drug effects , Humans , Antioxidants/chemistry , Antioxidants/pharmacology , Antioxidants/metabolism , Protons , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Reactive Oxygen Species/metabolism , Hydrogen/chemistry , Hydrogen/metabolism , Animals , Oxidative Stress/drug effectsABSTRACT
Tendon injuries are pervasive orthopedic injuries encountered by the general population. Nonetheless, recovery after severe injuries, such as Achilles tendon injury, is limited. Consequently, there is a pressing need to devise interventions, including biomaterials, that foster tendon healing. Regrettably, tissue engineering treatments have faced obstacles in crafting appropriate tissue scaffolds and efficacious nanomedical approaches. To surmount these hurdles, an innovative injectable hydrogel (CP@SiO2), comprising puerarin and chitosan through in situ self-assembly, is pioneered while concurrently delivering mesoporous silica nanoparticles for tendon healing. In this research, CP@SiO2 hydrogel is employed for the treatment of Achilles tendon injuries, conducting extensive in vivo and in vitro experiments to evaluate its efficacy. This reults demonstrates that CP@SiO2 hydrogel enhances the proliferation and differentiation of tendon-derived stem cells, and mitigates inflammation through the modulation of macrophage polarization. Furthermore, using histological and behavioral analyses, it is found that CP@SiO2 hydrogel can improve the histological and biomechanical properties of injured tendons. This findings indicate that this multifaceted injectable CP@SiO2 hydrogel constitutes a suitable bioactive material for tendon repair and presents a promising new strategy for the clinical management of tendon injuries.
ABSTRACT
Metal organic framework (MOF) films have attracted abundant attention due to their unique characters compared with MOF particles. But the high-temperature reaction and solvent corrosion limit the preparation of MOF films on fragile substrates, hindering further applications. Fabricating macro-sized continuous free-standing MOF films and transferring them onto fragile substrates are a promising alternative but still challenging. Here, a universal strategy to prepare transferrable macro-sized continuous free-standing MOF films with the assistance of oxide nanomembranes prepared by atomic layer deposition and studied the growth mechanism is developed. The oxide nanomembranes serve not only as reactant, but also as interfacial layer to maintain the integrality of the free-standing structure as the stacked MOF particles are supported by the oxide nanomembrane. The centimeter-scale free-standing MOF films can be transferred onto fragile substrates, and all in one device for glucose sensing is assembled. Due to the strong adsorption toward glucose molecules, the obtained devices exhibit outstanding performance in terms of high sensitivity, low limit of detection, and long durability. This work opens a new window toward the preparation of MOF films and MOF film-based biosensor chip for advantageous applications in post-Moore law period.
Subject(s)
Biosensing Techniques , Metal-Organic Frameworks , Metal-Organic Frameworks/chemistry , Biosensing Techniques/methods , Biosensing Techniques/instrumentation , Glucose , Equipment Design/methodsABSTRACT
Promoting metallic magnesium (Mg)-based implants to treat bone diseases in clinics, such as osteosarcoma and bacterial infection, remains a challenging topic. Herein, an iron hydroxide-based composite coating with a two-stage nanosheet-like structure was fabricated on Mg alloy, and this was followed by a thermal reduction treatment to break some of the surface Fe-OH bonds. The coating demonstrated three positive changes in properties due to the defects. First, the removal of -OH made the coating superhydrophobic, and it had self-cleaning and antifouling properties. This is beneficial for keeping the implants clean and for anti-corrosion before implantation into the human body. Furthermore, the superhydrophobicity could be removed by immersing the implant in a 75% ethanol solution, to further facilitate biological action during service. Second, the color of the coating changed from yellow to brown-black, leading to an increase in the light absorption, which resulted in an excellent photothermal effect. Third, the defects increased the Fe2+ content in the coating and highly improved peroxidase activity. Thus, the defect coating exhibited synergistic photothermal/chemodynamic therapeutic effects for bacteria and tumors. Moreover, the coating substantially enhanced the anti-corrosion and biocompatibility of the Mg alloys. Therefore, this study offers a novel multi-functional Mg-based implant for osteosarcoma therapy.
ABSTRACT
There is an evident advantage in personalized customization of orthopedic implants by 3D-printed titanium (Ti) and its alloys. However, 3D-printed Ti alloys have a rough surface structure caused by adhesion powders and a relatively bioinert surface. Therefore, surface modification techniques are needed to improve the biocompatibility of 3D-printed Ti alloy implants. In the present study, porous Ti6Al4V scaffolds were manufactured by a selective laser melting 3D printer, followed by sandblasting and acid-etching treatment and atomic layer deposition (ALD) of tantalum oxide films. SEM morphology and surface roughness tests confirmed that the unmelted powders adhered on the scaffolds were removed by sandblasting and acid-etching. Accordingly, the porosity of the scaffold increased by about 7%. Benefiting from the self-limitation and three-dimensional conformance of ALD, uniform tantalum oxide films were formed on the inner and outer surfaces of the scaffolds. Zeta potential decreased by 19.5 mV after depositing tantalum oxide films. The in vitro results showed that the adhesion, proliferation, and osteogenic differentiation of rat bone marrow mesenchymal stem cells on modified Ti6Al4V scaffolds were significantly enhanced, which may be ascribed to surface structure optimization and the compatibility of tantalum oxide. This study provides a strategy to improve the cytocompatibility and osteogenic differentiation of porous Ti6Al4V scaffolds for orthopedic implants.
Subject(s)
Osteogenesis , Titanium , Rats , Animals , Titanium/pharmacology , Titanium/chemistry , Powders , Printing, Three-Dimensional , AlloysABSTRACT
One of the main illnesses that put people's health in jeopardy is myocardial infarction (MI). After MI, damaged or dead cells set off an initial inflammatory response that thins the ventricle wall and degrades the extracellular matrix. At the same time, the ischemia and hypoxic conditions resulting from MI lead to significant capillary obstruction and rupture, impairing cardiac function and reducing blood flow to the heart. Therefore, attenuating the initial inflammatory response and promoting angiogenesis are very important for the treatment of MI. Here, to reduce inflammation and promote angiogenesis in infarcted area, we report a new kind of injectable hydrogel composed of puerarin and chitosan via in situ self-assembly with simultaneous delivery of mesoporous silica nanoparticles (CHP@Si) for myocardial repair. On the one hand, puerarin degraded from CHP@Si hydrogel modulated the inflammatory response via inhibiting M1-type polarization of macrophages and expression of pro-inflammatory factors. On the other hand, silica ions and puerarin released from CHP@Si hydrogel showed synergistic activity to improve the cell viability, migration and angiogenic gene expression of HUVECs in both conventional and oxygen/glucose-deprived environments. It suggests that this multifunctional injectable CHP@Si hydrogel with good biocompatibility may be an appropriate candidate as a bioactive material for myocardial repair post-MI.
ABSTRACT
Nanomaterials with photothermal combined chemodynamic therapy (PTT-CDT) have attracted the attention of researchers owing to their excellent synergistic therapeutic effects on tumors. Thus, the preparation of multifunctional materials with higher photothermal conversion efficiency and catalytic activity can achieve better synergistic therapeutic effects for melanoma. In this study, a Cu-Zn bimetallic single-atom (Cu/PMCS) is constructed with augmented photothermal effect and catalytic activity due to the localized surface plasmon resonance (LSPR) effect. Density functional theory calculations confirmed that the enhanced photothermal effect of Cu/PMCS is due to the appearance of a new d-orbital transition with strong spin-orbit coupling and the induced LSPR. Additionally, Cu/PMCS exhibited increased catalytic activity in the Fenton-like reaction and glutathione depletion capacity, further enhanced by increased temperature and LSPR. Consequently, Cu/PMCS induced better synergistic anti-melanoma effects via PTT-CDT than PMCS in vitro and in vivo. Furthermore, compared with PMCS, Cu/PMCS killed bacteria more quickly and effectively, thus facilitating wound healing owing to the enhanced photothermal effect and slow release of Cu2+ . Cu/PMCS promoted cell migration and angiogenesis and upregulated the expression of related genes to accelerate wound healing. Cu/PMCS has potential applications in treating melanoma and repairing wounds with its antitumor, antibacterial, and wound-healing properties.
Subject(s)
Copper , Melanoma , Humans , Surface Plasmon Resonance , Melanoma/therapy , Anti-Bacterial Agents , ZincABSTRACT
Ever-evolving advancements in films have fueled many of the developments in the field of electrochemical sensors. For biosensor application platforms, the fabrication of metal-organic framework (MOF) films on microscopically structured substrates is of tremendous importance. However, fabrication of MOF film-based electrodes always exhibits unsatisfactory performance, and the mechanisms of the fabrication and sensing application of the corresponding composites also need to be explored. Here, we report the fabrication of conformal MIL-53 (Fe) films on carbonized natural seaweed with the assistance of an oxide nanomembrane and a potential-dependent electrochemical dopamine (DA) sensor. The geometry and structure of the composite can be conveniently tuned by the experimental parameters, while the sensing performance is significantly influenced by the applied potential. The obtained sensor demonstrates ultrahigh sensitivity, a wide linear range, a low limit of detection, and a good distinction between DA and ascorbic acid at an optimized potential of 0.3 V. The underneath mechanism is investigated in detail with the help of theoretical calculations. This work bridges the natural material and MOF films and is promising for future biosensing applications.
Subject(s)
Biosensing Techniques , Metal-Organic Frameworks , Metal-Organic Frameworks/chemistry , Carbon/chemistry , Dopamine/chemistry , Oxides , Electrodes , Electrochemical TechniquesABSTRACT
The combination of photothermal treatment and chemodynamic therapy has attracted extensive attention for improving therapeutic effects and compensating the insufficiency of monotherapy. In this work, a copper-metal organic framework (Cu-BTC) was used to augment the photothermal effect of polydopamine (PDA) and endow it with a chemodynamic ability by constructing a Cu-BTC@PDA nanocomposite. Density functional theory calculations revealed that the plasmonic vibrations formed by the d-d transition of Cu at the Fermi level in Cu-BTC@PDA could enhance the photothermal performance of PDA. In addition, more Cu2+ released from Cu-BTC@PDA in the acidic microenvironment of the tumor was then reduced to Cu+ by glutathione (GSH) and further catalyzed H2O2 to generate more toxic hydroxyl radical (â¢OH), which synergized with photothermal treatment for melanoma therapy. Furthermore, Cu-BTC@PDA could quickly and effectively kill bacteria under the action of PTT, and the sustained release of Cu ions could contribute to the long-term and stable bacteriostatic ability of the material. This sustained release of Cu ions could also promote the cell migration and angiogenesis, and upregulate the expression of COL-, TGF-, and VEGF-related genes to accelerate wound healing. This multifunctional nanomaterial has potential application in the treatment of melanoma and repair of wounds. STATEMENT OF SIGNIFICANCE: We constructed a multifunctional nanoplatform (Cu-BTC@PDA) by two steps. This nanoplatform can not only perform cascade catalysis in the tumor microenvironment to generate more toxic hydroxyl radical (â¢OH), but also synergize with photothermal treatment for melanoma therapy. Additionally, Cu-BTC@PDA possesses enhanced photothermal performance through the plasmonic vibrations formed by the d-d transition of Cu at the Fermi level in Cu-BTC@PDA, which is revealed by DFT calculations. And Cu-BTC@PDA shows good antitumor, antibacterial, and wound healing properties in vivo and in vitro. Such a multifunctional nanomaterial has potential application in the treatment of melanoma and repair of wounds.
Subject(s)
Melanoma , Metal-Organic Frameworks , Nanoparticles , Humans , Cell Line, Tumor , Copper/pharmacology , Delayed-Action Preparations , Glutathione , Hydrogen Peroxide , Hydroxyl Radical , Melanoma/drug therapy , Metal-Organic Frameworks/pharmacology , Tumor MicroenvironmentABSTRACT
Intelligent control of the immune response is essential for obtaining percutaneous implants with good sterilization and tissue repair abilities. In this study, polypyrrole (Ppy) nanoparticles enveloping a 3D frame of sulfonated polyether ether ketone (SP) surface are constructed, which enhance the surface modulus and hardness of the sulfonated layer by forming a cooperative structure of simulated reinforced concrete and exhibit a superior photothermal effect. Ppy-coated SP could quickly accumulate heat on the surface by responding to 808 nm near-infrared (NIR) light, thereby killing bacteria, and destroying biofilms. Under NIR stimulation, the phagocytosis and M1 activation of macrophages cultured on Ppy-coated SP are enhanced by activating complement 3 and its receptor, CD11b. Phagocytosis and M1 activation are impaired along with abolishment of NIR stimulation in the Ppy-coated SP group, which is favorable for tissue repair. Ppy-coated SP promotes Collagen-I, vascular endothelial growth factor, connective tissue growth factor, and α-actin (Acta2) expression by inducing M2 polarization owing to its higher surface modulus. Overall, Ppy-coated SP with enhanced mechanical properties could be a good candidate for clinical percutaneous implants through on-off phagocytosis and switchable macrophage activation stimulated with NIR.
Subject(s)
Infrared Rays , Macrophage Activation , Nanoparticles , Phagocytosis , Polymers , Pyrroles , Ketones , Macrophage Activation/radiation effects , Phagocytosis/radiation effects , Polyethylene Glycols , Polymers/chemistry , Pyrroles/chemistry , Vascular Endothelial Growth Factor A , Infrared Rays/therapeutic use , Nanoparticles/therapeutic use , Mice , AnimalsABSTRACT
The repair of bone defects caused by osteosarcoma resection remains a clinical challenge because of the tumor recurrence and bacterial infection. Combining tumor and bacterial therapy with bone regeneration properties in bone implants is a promising strategy for the treatment of osteosarcoma. Here, a layer of MgO/FeOx nanosheet is constructed on the Ti implant to prevent tumor recurrence and bacterial infection, while simultaneously accelerating bone formation. This MgO/FeOx double metal oxide demonstrates good peroxidase activity to catalyze H2 O2 , which is rich in tumor microenvironment, to form reactive oxygen species (ROS), and shows good photothermal conversion capacity to produce photothermal effect, thus synergistically killing tumor cells and eliminating tumor tissue. In addition, it generates a local alkaline surface microenvironment to inhibit the energy metabolism of bacteria to enhance the photothermal antibacterial effect. Furthermore, benefiting from the generation of a Mg ion-containing alkaline microenvironment, this MgO/FeOx film can promote the osteogenic differentiation of osteoblast and angiogenesis of vascular endothelial cells in vitro as well as accelerated bone formation in vivo. This study proposes a multifunctional platform for integrating tumor and bacterial therapy and bone regeneration, which has good application prospects for the treatment of osteosarcoma.
Subject(s)
Bacterial Infections , Bone Neoplasms , Osteosarcoma , Humans , Titanium/pharmacology , Osteogenesis , Magnesium Oxide , Endothelial Cells , Neoplasm Recurrence, Local , Bone Regeneration , Osteosarcoma/therapy , Bone Neoplasms/therapy , Tumor MicroenvironmentABSTRACT
Implantable biomaterials are widely used in the curative resection and palliative treatment of various types of cancers. However, cancer residue around the implants usually leads to treatment failure with cancer reoccurrence. Postoperation chemotherapy and radiation therapy are widely applied to clear the residual cancer cells but induce serious side effects. It is urgent to develop advanced therapy to minimize systemic toxicity while maintaining efficient cancer-killing ability. Herein, we report a degenerate layered double hydroxide (LDH) film modified implant, which realizes microenvironment-responsive electrotherapy. The film can gradually transform into a nondegenerate state and release holes. When in contact with tumor cells or bacteria, the film quickly transforms into a nondegenerate state and releases holes at a high rate, rendering the "electrocution" of tumor cells and bacteria. However, when placed in normal tissue, the hole release rate of the film is much slower, thus, causing little harm to normal cells. Therefore, the constructed film can intelligently identify and meet the physiological requirements promptly. In addition, the transformation between degenerate and nondegenerate states of LDH films can be cycled by electrical charging, so their selective and dynamic physiological functions can be artificially adjusted according to demand.
ABSTRACT
Wound healing is one of the major global health concerns in patients with diabetes. Overactivation of pro-inflammatory M1 macrophages is associated with delayed wound healing in diabetes. miR-29ab1 plays a critical role in diabetes-related macrophage inflammation. Hence, inhibition of inflammation and regulation of miR-29 expression have been implicated as new points for skin wound healing. In this study, the traditional Chinese medicine, puerarin, was introduced to construct an injectable and self-healing chitosan@puerarin (C@P) hydrogel. The C@P hydrogel promoted diabetic wound healing and accelerated angiogenesis, which were related to the inhibition of the miR-29 mediated inflammation response. Compared to healthy subjects, miR-29a and miR-29b1 were ectopically increased in the skin wound of the diabetic model, accompanied by upregulated M1-polarization, and elevated levels of IL-1ß and TNF-α. Further evaluations by miR-29ab1 knockout mice exhibited superior wound healing and attenuated inflammation. The present results suggested that miR-29ab1 is essential for diabetic wound healing by regulating the inflammatory response. Suppression of miR-29ab1 by the C@P hydrogel has the potential for improving medical approaches for wound repair.