Manganese-containing Bioactive Glass Enhances Osteogenic Activity of TiO2 Nanotube Arrays.

Titanium and its alloys are the most used biomaterials for orthopedic and dental applications. However, up to 10% of these medical devices still fail, mostly due to implant loosening and suboptimal integration at the implant site. The biomaterial surface plays a critical role in promoting osseointegration, which can reduce the risk of device failure. In this study, we propose a novel surface modification on titanium to improve osteogenic differentiation by depositing manganese-containing bioactive glass (BG) on TiO2 nanotube arrays. The surfaces were characterized by scanning electron microscopy, energy dispersive X-ray spectrometer, contact angle goniometry, and X-ray photoelectron spectroscopy. Cell toxicity, viability, adhesion, and proliferation of adipose-derived stem cells on the surfaces were investigated up to 7 days. To evaluate the osteogenic properties of the surfaces, alkaline phosphatase activity, total protein, osteocalcin expression, and calcium deposition were quantified up to 28 days. The results indicate that TiO2 nanotube arrays modified with BG promote cell growth and induce increased osteocalcin and calcium contents when compared to unmodified TiO2 nanotube arrays. The deposition of manganese-containing bioactive glass onto TiO2 nanotubes demonstrates the ability to enhance osteogenic activity on titanium, showing great potential for use in orthopedic and dental implants.

Cell investigation into the biocompatibility of adult human dermal fibroblasts with PCL nanofibers/TiO2 nanotubes on the surface of Ti-30Ta alloy for biomedical applications.

The polymer poly(ε-caprolactone) (PCL) has been used in the biomaterial field for its relatively inexpensive price and suitability for modification. Also, its chemical and biological properties are desirable for biomedical applications. The electrospinning process has been used for producing polymer fibers of PCL due in large part to an increased interest in nanoscale properties and technologies. Moreover, the use of biocompatible polymers for the viability of cell growth is a promising alternative to improve osseointegration. Characterization techniques such as scanning electron microscopy and contact angle were used for analyses of samples. Adult human dermal fibroblasts (neonatal) were utilized to evaluate the biocompatibility of the association of the electrospinning process of the biocompatible polymer (PCL) with TiO2 nanotubes on the Ti-30Ta alloy surface. The results of this study showed a favorable response for adhesion on the surface. This promising material is due to the modulation of the biological response.

Crystallinity of TiO2 nanotubes and its effects on fibroblast viability, adhesion, and proliferation.

Titanium and titanium alloys are widely used as a biomaterial due to their mechanical strength, corrosion resistance, low elastic modulus, and excellent biocompatibility. TiO2 nanotubes have excellent bioactivity, stimulating the adhesion, proliferation of fibroblasts and adipose-derived stem cells, production of alkaline phosphatase by osteoblasts, platelets activation, growth of neural cells and adhesion, spreading, growth, and differentiation of rat bone marrow mesenchymal stem cells. In this study, we investigated the functionality of fibroblast on titania nanotube layers annealed at different temperatures. The titania nanotube layer was fabricated by potentiostatic anodization of titanium, then annealed at 300, 530, and 630 °C for 5 h. The resulting nanotube layer was characterized using SEM (Scanning Electron Microscopy), TF-XRD (Thin-film X-ray diffraction), and contact angle goniometry. Fibroblasts viability was determined by the CellTiter-Blue method and cytotoxicity by Lactate Dehydrogenase test, and the cell morphology was analyzed by scanning electron microscopy. Also, cell adherence, proliferation, and morphology were analyzed by fluorescence microscopy. The results indicate that the modification in nanotube crystallinity may provide a favorable surface fibroblast growth, especially on substrates annealed at 530 and 630 °C, indicating that these properties provide a favorable template for biomedical implants.

Bactericidal Pectin/Chitosan/Glycerol Films for Food Pack Coatings: A Critical Viewpoint.

Pectin and chitosan films containing glycerol (Gly) at 5, 10, 15, 20, 30, and 40 wt % were prepared in an aqueous HCl solution (0.10 M) by the solvent evaporation method. The unwashed film (UF) containing 40 wt % Gly (UF40) had elongation at break (ε, %) of 19%. Washed films (WFs) had high tensile strength (σ > 46 MPa) and low elongation at break (ε, <5.0%), enabling their use in food packaging applications. The polymers' self-assembling occurred during the washing, increasing the stiffness. The XPS analysis suggests that some HCl is lost during the drying process, resulting in a low acid content on the UF surfaces. The UF40 (at 5.0 mg/mL) exhibits cytocompatibility toward mammalian cells and antimicrobial and anti-adhesive properties against Escherichia coli. The remaining HCl in the UF40 can be a disadvantage for food packaging applications; the UF40 (∅ = 8.5 mm; 55 µm thickness) releases H3O+/HCl, reducing the pH to approximately 3.0 when kept in 200 mL distilled water for approximately 30 min. Therefore, we propose the use of UF40 to coat commercial food packaging. The UF40 has low permeability to water vapor and oxygen and works as a barrier against ultraviolet light. The UF40 is also colorless and completely transparent. The UF40 maintained tomatoes' structural integrity for 18 days at room temperature with no oxidation or microorganism contamination. This paper presents a critical viewpoint concerning chitosan-based films with antimicrobial activities.

Effects of titania nanotube surfaces on osteogenic differentiation of human adipose-derived stem cells.

The surface of an implant is important for successful osseointegration and long-term stability as it can aid in cell migration and proliferation, cell differentiation and allow extracellular matrix production. Earlier studies have shown that nanostructuring the surface of titanium can enhance mesenchymal stem cell (MSC) migration, proliferation, and differentiation. Although many studies have evaluated MSC response on nanostructured surfaces, there are only a few studies that have explored the response of adipose-derived stem cells (ADSC) on titania nanotube surfaces. Because ADSC exhibit great potential in regenerative medicine and have already proven effective in developing new treatments, this study aims to further understand how ADSC interact with titania nanotube surfaces. The results of this study indicate that titania nanotube surfaces enhance ADSC proliferation and differentiation that is also dependent on the size of nanotubes. Additionally, the favorable response of ADSC on nanotube surfaces suggests a potential application in orthopedic tissue regeneration.

Interaction of blood plasma proteins with superhemophobic titania nanotube surfaces.

The need to improve blood biocompatibility of medical devices is urgent. As soon as blood encounters a biomaterial implant, proteins adsorb on its surfaces, often leading to several complications such as thrombosis and failure of the device. Therefore, controlling protein adsorption plays a major role in developing hemocompatible materials. In this study, the interaction of key blood plasma proteins with superhemophobic titania nanotube substrates and the blood clotting responses was investigated. The substrate stability was evaluated and fibrinogen adsorption and thrombin formation from plasma were assessed using ELISA. Whole blood clotting kinetics was also investigated, and Factor XII activation on the substrates was characterized by an in vitro plasma coagulation time assay. The results show that superhemophobic titania nanotubes are stable and considerably decrease surface protein adsorption/Factor XII activation as well as delay the whole blood clotting, and thus can be a promising approach for designing blood contacting medical devices.

Titania (TiO2) nanotube surfaces doped with zinc and strontium for improved cell compatibility.

Titanium-based orthopedic implants are gaining popularity in recent years due to their excellent biocompatibility, superior corrosion resistance and lightweight properties. However, these implants often fail to perform effectively due to poor osseointegration. Nanosurface modification approaches may help to resolve this problem. In this work, TiO2 nanotube (NT) arrays were fabricated on commercially available pure titanium (Ti) surfaces by anodization and annealing. Then, zinc (Zn) and strontium (Sr), important for cell signaling, were doped on the NT surface by hydrothermal treatment. This very simple method of Zn and Sr doping takes less time and energy compared to other complicated techniques. Different surface characterization tools such as scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), energy-dispersive X-ray spectroscopy (EDS), static water contact angle, X-ray diffraction (XRD) and nanoindentation techniques were used to evaluate the modified surfaces. Then, adipose derived stem cells (ADSCs) were cultured with the surfaces to evaluate cell adhesion, proliferation, and growth on the surfaces. After that, the cells were differentiated towards osteogenic lineage to evaluate alkaline phosphatase (ALP) activity, osteocalcin expression, and calcium phosphate mineralization. Results indicate that NT surfaces doped with Zn and Sr had significantly enhanced ADSC adhesion, proliferation, growth, and osteogenic differentiation compared to an unmodified surface, thus confirming the enhanced performance of these surfaces.

Surface modification strategies for improved hemocompatibility of polymeric materials: a comprehensive review.

Polymeric biomaterials are a widely used class of materials due to their versatile properties. However, as with all other types of materials used for biomaterials, polymers also have to interact with blood. When blood comes into contact with any foreign body, it initiates a cascade which leads to platelet activation and blood coagulation. The implant surface also has to encounter a thromboinflammatory response which makes the implant integrity vulnerable, this leads to blood coagulation on the implant and obstructs it from performing its function. Hence, the surface plays a pivotal role in the design and application of biomaterials. In particular, the surface properties of biomaterials are responsible for biocompatibility with biological systems and hemocompatibility. This review provides a report on recent advances in the field of surface modification approaches for improved hemocompatibility. We focus on the surface properties of polysaccharides, proteins, and synthetic polymers. The blood coagulation cascade has been discussed and blood - material surface interactions have also been explained. The interactions of blood proteins and cells with polymeric material surfaces have been discussed. Moreover, the benefits as well as drawbacks of blood coagulation on the implant surface for wound healing purposes have also been studied. Surface modifications implemented by other researchers to enhance as well as prevent blood coagulation have also been analyzed.

Excellent Electroluminescent Property of Eu3+-Induced Polystyrene-co-poly(acrylic acid) Aggregates (EIPAs) in Polymeric Light-Emitting Diodes.

Eu3+-induced polystyrene-co-poly(acrylic acid) aggregates (EIPAs) were synthesized using a self-assembly approach, and their structures and photophysical characteristics were examined to achieve effective monochromatic red emission in polymer light-emitting diodes (PLEDs). By adjusting the monomer ratio in RAFT polymerization, the size of Eu3+-induced block copolymer nanoaggregates can be regulated, thereby modulating the luminescence intensity. High-performance bilayer polymer light-emitting devices were fabricated using poly(9,9-dioctylfluorene) (PFO) and 2-(tert-butylphenyl)-5-biphenylyl-1,3,4-oxadiazole (PBD) as the host matrix, with EIPAs as the guest dopant. The devices exhibited narrow red emission at 615 nm with a full width at half-maximum (fwhm) of 15 nm across doping concentrations of 1, 3, 5, and 10 wt %. At a doping concentration of 3 wt %, the device achieved a maximum brightness of 1864.48 cd/m2 at 193.82 mA/cm2 and an external quantum efficiency of 3.20% at a current density of 3.5 mA/cm2. These results indicate that incorporating polystyrene-co-poly(acrylic acid) with Eu3+ complexes enhances the excitation and emission intensity, as well as the structural stability of the emitting layer in PLEDs, thereby improving the device performance.

Zinc (Zn) Doping by Hydrothermal and Alkaline Heat-Treatment Methods on Titania Nanotube Arrays for Enhanced Antibacterial Activity.

Titanium (Ti) is a popular biomaterial for orthopedic implant applications due to its superior mechanical properties such as corrosion resistance and low modulus of elasticity. However, around 10% of these implants fail annually due to bacterial infection and poor osseointegration, resulting in severe pain and suffering for the patients. To improve their performance, nanoscale surface modification approaches and doping of trace elements on the surfaces can be utilized which may help in improving cell adhesion for better osseointegration while reducing bacterial infection. In this work, at first, titania (TiO2) nanotube arrays (NT) were fabricated on commercially available pure Ti surfaces via anodization. Then zinc (Zn) doping was conducted following two distinct methods: hydrothermal and alkaline heat treatment. Scanning electron microscopic (SEM) images of the prepared surfaces revealed unique surface morphologies, while energy dispersive X-ray spectroscopy (EDS) revealed Zn distribution on the surfaces. Contact angle measurements indicated that NT surfaces were superhydrophilic. X-ray photoelectron spectroscopy (XPS) provided the relative amount of Zn on the surfaces and indicated that hydrothermally treated surfaces had more Zn compared to the alkaline heat-treated surfaces. X-ray crystallography (XRD) and nanoindentation techniques provided the crystal structure and mechanical properties of the surfaces. While testing with adipose-derived stem cells (ADSC), the surfaces showed no apparent cytotoxicity to the cells. Finally, bacteria adhesion and morphology were evaluated on the surfaces after 6 h and 24 h of incubation. From the results, it was confirmed that NT surfaces doped with Zn drastically reduced bacteria adhesion compared to the Ti control. Zn-doped NT surfaces thus offer a potential platform for orthopedic implant application.

Antifouling Behavior of Copper-Modified Titania Nanotube Surfaces.

Titanium and its alloys are commonly used to fabricate orthopedic implants due to their excellent mechanical properties, corrosion resistance, and biocompatibility. In recent years, orthopedic implant surgeries have considerably increased. This has also resulted in an increase in infection-associated revision surgeries for these implants. To combat this, various approaches are being investigated in the literature. One of the approaches is modifying the surface topography of implants and creating surfaces that are not only antifouling but also encourage osteointegration. Titania nanotube surfaces have demonstrated a moderate decrease in bacterial adhesion while encouraging mesenchymal stem cell adhesion, proliferation, and differentiation, and hence were used in this study. In this work, titania nanotube surfaces were fabricated using a simple anodization technique. These surfaces were further modified with copper using a physical vapor deposition technique, since copper is known to be potent against bacteria once in contact. In this study, scanning electron microscopy was used to evaluate surface topography; energy-dispersive X-ray spectroscopy and X-ray photoelectron spectroscopy were used to evaluate surface chemistry; contact angle goniometry was used to evaluate surface wettability; and X-ray diffraction was used to evaluate surface crystallinity. Antifouling behavior against a gram-positive and a gram-negative bacterium was also investigated. The results indicate that copper-modified titania nanotube surfaces display enhanced antifouling behavior when compared to other surfaces, and this may be a potential way to prevent infection in orthopedic implants.

Recent Advances in Tissue-Engineered Cardiac Scaffolds-The Progress and Gap in Mimicking Native Myocardium Mechanical Behaviors.

Heart failure is the leading cause of death in the US and worldwide. Despite modern therapy, challenges remain to rescue the damaged organ that contains cells with a very low proliferation rate after birth. Developments in tissue engineering and regeneration offer new tools to investigate the pathology of cardiac diseases and develop therapeutic strategies for heart failure patients. Tissue -engineered cardiac scaffolds should be designed to provide structural, biochemical, mechanical, and/or electrical properties similar to native myocardium tissues. This review primarily focuses on the mechanical behaviors of cardiac scaffolds and their significance in cardiac research. Specifically, we summarize the recent development of synthetic (including hydrogel) scaffolds that have achieved various types of mechanical behavior-nonlinear elasticity, anisotropy, and viscoelasticity-all of which are characteristic of the myocardium and heart valves. For each type of mechanical behavior, we review the current fabrication methods to enable the biomimetic mechanical behavior, the advantages and limitations of the existing scaffolds, and how the mechanical environment affects biological responses and/or treatment outcomes for cardiac diseases. Lastly, we discuss the remaining challenges in this field and suggestions for future directions to improve our understanding of mechanical control over cardiac function and inspire better regenerative therapies for myocardial restoration.

Expanding the Scope of an Amphoteric Condensed Tannin, Tanfloc, for Antibacterial Coatings.

Bacterial infections are a common mode of failure for medical implants. This study aims to develop antibacterial polyelectrolyte multilayer (PEM) coatings that contain a plant-derived condensed tannin polymer (Tanfloc, TAN) with inherent antimicrobial activity. Tanfloc is amphoteric, and herein we show that it can be used as either a polyanion or a polycation in PEMs, thereby expanding the possibility of its use in PEM coatings. PEMs are ordinarily formed using a polycation and a polyanion, in which the functional (ionic) groups of the two polymers are complexed to each other. However, using the amphoteric polymer Tanfloc with weakly basic amine and weakly acidic catechol and pyrogallol groups enables PEM formation using only one or the other of its functional groups, leaving the other functional group available to impart antibacterial activity. This work demonstrates Tanfloc-containing PEMs using multiple counter-polyelectrolytes including three polyanionic glycosaminoglycans of varying charge density, and the polycations N,N,N-trimethyl chitosan and polyethyleneimine. The layer-by-layer (LbL) assembly of PEMs was monitored using in situ Fourier-transform surface plasmon resonance (FT-SPR), confirming a stable LbL assembly. X-ray photoelectron spectroscopy (XPS) was used to evaluate surface chemistry, and atomic force microscopy (AFM) was used to determine the surface roughness. The LDH release levels from cells cultured on the Tanfloc-containing PEMs were not statistically different from those on the negative control (p > 0.05), confirming their non-cytotoxicity, while exhibiting remarkable antiadhesive and bactericidal properties against Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus), respectively. The antibacterial effects were attributed to electrostatic interactions and Tanfloc's polyphenolic nature. This work underscores the potential of Tanfloc as a versatile biomaterial for combating infections on surfaces.

Antimicrobial and Antiproliferative Coatings for Stents in Veterinary Medicine-State of the Art and Perspectives.

Microbial colonization in veterinary stents poses a significant and concerning issue in veterinary medicine. Over time, these pathogens, particularly bacteria, can colonize the stent surfaces, leading to various complications. Two weeks following the stent insertion procedure, the colonization becomes observable, with the aggressiveness of bacterial growth directly correlating with the duration of stent placement. Such microbial colonization can result in infections and inflammations, compromising the stent's efficacy and, subsequently, the animal patient's overall well-being. Managing and mitigating the impact of these pathogens on veterinary stents is a crucial challenge that veterinarians and researchers are actively addressing to ensure the successful treatment and recovery of their animal patients. In addition, irritation of the tissue in the form of an inserted stent can lead to overgrowth of granulation tissue, leading to the closure of the stent lumen, as is most often the case in the trachea. Such serious complications after stent placement require improvements in the procedures used to date. In this review, antibacterial or antibiofilm strategies for several stents used in veterinary medicine have been discussed based on the current literature and the perspectives have been drawn. Various coating strategies such as coating with hydrogel, antibiotic, or other antimicrobial agents have been reviewed.

Ligand Presentation Inside Protein Crystal Nanopores: Tunable Interfacial Adhesion Noncovalently Modulates Cell Attachment.

Protein crystals with sufficiently large solvent pores can non-covalently adsorb polymers in the pores. In principle, if these polymers contain cell adhesion ligands, the polymer-laden crystals could present ligands to cells with tunable adhesion strength. Moreover, porous protein crystals can store an internal ligand reservoir, so that the surface can be replenished. In this study, we demonstrate that poly(ethylene glycol) terminated with a cyclic cell adhesion ligand peptide (PEG-RGD) can be loaded into porous protein crystals by diffusion. Through atomic force microscopy (AFM), force-distance correlations of the mechanical interactions between activated AFM tips and protein crystals were precisely measured. The activation of AFM tips allows the tips to interact with PEG-RGD that was pre-loaded in the protein crystal nanopores, mimicking how a cell might attach to and pull on the ligand through integrin receptors. The AFM experiments also simultaneously reveal the detailed morphology of the buffer-immersed nanoporous protein crystal surface. We also show that porous protein crystals (without and with loaded PEG-RGD) serve as suitable substrates for attachment and spreading of adipose-derived stem cells. This strategy can be used to design surfaces that non-covalently present multiple different ligands to cells with tunable adhesive strength for each ligand, and with an internal reservoir to replenish the precisely defined crystalline surface.

Hemp-Based Sustainable Slippery Surfaces: Icephobic and Antithrombotic Properties.

With the passage of the 2018 Farm Bill that removed hemp from the Controlled Substances Act altogether, production of hemp is experiencing a renaissance. Building on this revival and re-emergence of hemp, we designed and fabricated hemp-based sustainable and robust slippery surfaces by coating hemp paper with beeswax and subsequently infusing it with hemp oil. A wide variety of aqueous liquids and beverages easily slide on our hemp-based sustainable slippery surfaces, without leaving a trace. We also fabricated hemp-based sustainable slippery surfaces using different textured metals. Our hemp-based sustainable slippery metal surfaces display good icephobic and antithrombotic properties. With these attributes, we envision that our hemp-based sustainable slippery surfaces will pave the path to more safe, non-toxic, and biodegradable or recyclable slippery surfaces for applications in food packaging, anti-icing or de-icing coatings, and antithrombotic medical devices.

Oxygen-Vacancy Abundant Nanoporous Ni/NiMnO3/MnO2@NiMn Electrodes with Ultrahigh Capacitance and Energy Density for Supercapacitors.

High-performance energy storage devices (HPEDs) play a critical role in the realization of clean energy and thus enable the overarching pursuit of nonpolluting, green technologies. Supercapacitors are one class of such lucrative HPEDs; however, a serious limiting factor of supercapacitor technology is its sub-par energy density. This report presents hitherto unchartered pathway of physical deformation, chemical dealloying, and microstructure engineering to produce ultrahigh-capacitance, energy-dense NiMn alloy electrodes. The activated electrode delivered an ultrahigh specific-capacitance of 2700 F/cm3 at 0.5 A/cm3. The symmetric device showcased an excellent energy density of 96.94 Wh/L and a remarkable cycle life of 95% retention after 10,000 cycles. Transmission electron microscopy and atom probe tomography studies revealed the evolution of a unique hierarchical microstructure comprising fine Ni/NiMnO3 nanoligaments within MnO2-rich nanoflakes. Theoretical analysis using density functional theory showed semimetallic nature of the nanoscaled oxygen-vacancy-rich NiMnO3 structure, highlighting enhanced carrier concentration and electronic conductivity of the active region. Furthermore, the geometrical model of NiMnO3 crystals revealed relatively large voids, likely providing channels for the ion intercalation/de-intercalation. The current processing approach is highly adaptable and can be applied to a wide range of material systems for designing highly efficient electrodes for energy-storage devices.

Mechanical Properties, Corrosion Behavior, and In Vitro Cell Studies of the New Ti-25Ta-25Nb-5Sn Alloy.

This study aims to characterize a new Ti-25Ta-25Nb-5Sn alloy for biomedical application. Microstructure, phase formation, mechanical and corrosion properties, along with the cell culture study of the Ti-25Ta-25Nb alloy with Sn content 5 mass% are presented in this article. The experimental alloy was processed in an arc melting furnace, cold worked, and heat treated. For characterization, optical microscopy, X-ray diffraction, microhardness, and Young's modulus measurements were employed. Corrosion behavior was also evaluated using open-circuit potential (OCP) and potentiodynamic polarization. In vitro studies with human ADSCs were performed to investigate cell viability, adhesion, proliferation, and differentiation. Comparison among the mechanical properties observed in other metal alloy systems, including CP Ti, Ti-25Ta-25Nb, and Ti-25Ta-25-Nb-3Sn showed an increase in microhardness and a decrease in the Young's modulus when compared to CP Ti. The potentiodynamic polarization tests indicated that the corrosion resistance of the Ti-25Ta-25Nb-5Sn alloy was similar to CP Ti and the experiments in vitro demonstrated great interactions between the alloy surface and cells in terms of adhesion, proliferation, and differentiation. Therefore, this alloy presents potential for biomedical applications with properties required for good performance.

Carboxymethylcellulose hydrogels crosslinked with keratin nanoparticles for efficient prednisolone delivery.

Carboxymethylcellulose (CMC) and keratin nanoparticle (KNP) hydrogels were obtained, characterized, and applied as drug delivery systems (DDSs) for the first time. Lyophilized CMC/KNP mixtures containing 10, 25, and 50 wt% of KNPs were kept at 170 °C for 90 min to crosslink CMC chains through a solid-state reaction with the KNPs. The hydrogels were characterized by infrared spectroscopy, thermal analyses, X-ray diffraction, mechanical measurements, and scanning electron microscopy. The infrared spectra indicated the formation of ester and amide linkages between crosslinked CMC and KNPs. The elastic modulus of the hydrogel containing 10 wt% KNPs was 2-fold higher than that of the hydrogel containing 50 wt% KNPs. The mechanical properties influenced the hydrogel stability and water uptake. The anti-inflammatory prednisolone (PRED) drug was incorporated into the hydrogels, and the release mechanism was investigated. The hydrogels supported PRED release by drug desorption for approximately 360 h. A sustained release mechanism was achieved. The CMC/KNP and CMC/KNP/PRED hydrogels were cytocompatible toward mammalian cells. The CMC/KNP/PRED set imparted the highest cell viability after 7 days of incubation. This study showed a straightforward procedure to create DDSs (chemically crosslinked) based on polysaccharides and proteins for efficient PRED delivery.

Selective targeting of microglia by quantum dots.

BACKGROUND: Microglia, the resident immune cells of the brain, have been implicated in brain injury and various neurological disorders. However, their precise roles in different pathophysiological situations remain enigmatic and may range from detrimental to protective. Targeting the delivery of biologically active compounds to microglia could help elucidate these roles and facilitate the therapeutic modulation of microglial functions in neurological diseases. METHODS: Here we employ primary cell cultures and stereotaxic injections into mouse brain to investigate the cell type specific localization of semiconductor quantum dots (QDs) in vitro and in vivo. Two potential receptors for QDs are identified using pharmacological inhibitors and neutralizing antibodies. RESULTS: In mixed primary cortical cultures, QDs were selectively taken up by microglia; this uptake was decreased by inhibitors of clathrin-dependent endocytosis, implicating the endosomal pathway as the major route of entry for QDs into microglia. Furthermore, inhibiting mannose receptors and macrophage scavenger receptors blocked the uptake of QDs by microglia, indicating that QD uptake occurs through microglia-specific receptor endocytosis. When injected into the brain, QDs were taken up primarily by microglia and with high efficiency. In primary cortical cultures, QDs conjugated to the toxin saporin depleted microglia in mixed primary cortical cultures, protecting neurons in these cultures against amyloid beta-induced neurotoxicity. CONCLUSIONS: These findings demonstrate that QDs can be used to specifically label and modulate microglia in primary cortical cultures and in brain and may allow for the selective delivery of therapeutic agents to these cells.