Amnion-derived hydrogels as a versatile platform for regenerative therapy: from lab to market.

In recent years, the amnion (AM) has emerged as a versatile tool for stimulating tissue regeneration and has been of immense interest for clinical applications. AM is an abundant and cost-effective tissue source that does not face strict ethical issues for biomedical applications. The outstanding biological attributes of AM, including side-dependent angiogenesis, low immunogenicity, anti-inflammatory, anti-fibrotic, and antibacterial properties facilitate its usage for tissue engineering and regenerative medicine. However, the clinical usage of thin AM sheets is accompanied by some limitations, such as handling without folding or tearing and the necessity for sutures to keep the material over the wound, which requires additional considerations. Therefore, processing the decellularized AM (dAM) tissue into a temperature-sensitive hydrogel has expanded its processability and applicability as an injectable hydrogel for minimally invasive therapies and a source of bioink for the fabrication of biomimetic tissue constructs by recapitulating desired biochemical cues or pre-defined architectural design. This article reviews the multi-functionality of dAM hydrogels for various biomedical applications, including skin repair, heart treatment, cartilage regeneration, endometrium regeneration, vascular graft, dental pulp regeneration, and cell culture/carrier platform. Not only recent and cutting-edge research is reviewed but also available commercial products are introduced and their main features and shortcomings are elaborated. Besides the great potential of AM-derived hydrogels for regenerative therapy, intensive interdisciplinary studies are still required to modify their mechanical and biological properties in order to broaden their therapeutic benefits and biomedical applications. Employing additive manufacturing techniques (e.g., bioprinting), nanotechnology approaches (e.g., inclusion of various bioactive nanoparticles), and biochemical alterations (e.g., modification of dAM matrix with photo-sensitive molecules) are of particular interest. This review article aims to discuss the current function of dAM hydrogels for the repair of target tissues and identifies innovative methods for broadening their potential applications for nanomedicine and healthcare.

Review of sustainable, eco-friendly, and conductive polymer nanocomposites for electronic and thermal applications: current status and future prospects.

Biodegradable polymer nanocomposites (BPNCs) are advanced materials that have gained significant attention over the past 20 years due to their advantages over conventional polymers. BPNCs are eco-friendly, cost-effective, contamination-resistant, and tailorable for specific applications. Nevertheless, their usage is limited due to their unsatisfactory physical and mechanical properties. To improve these properties, nanofillers are incorporated into natural polymer matrices, to enhance mechanical durability, biodegradability, electrical conductivity, dielectric, and thermal properties. Despite the significant advances in the development of BPNCs over the last decades, our understanding of their dielectric, thermal, and electrical conductivity is still far from complete. This review paper aims to provide comprehensive insights into the fundamental principles behind these properties, the main synthesis, and characterization methods, and their functionality and performance. Moreover, the role of nanofillers in strength, permeability, thermal stability, biodegradability, heat transport, and electrical conductivity is discussed. Additionally, the paper explores the applications, challenges, and opportunities of BPNCs for electronic devices, thermal management, and food packaging. Finally, this paper highlights the benefits of BPNCs as biodegradable and biodecomposable functional materials to replace traditional plastics. Finally, the contemporary industrial advances based on an overview of the main stakeholders and recently commercialized products are addressed.

Engineering Photo-Cross-Linkable MXene-Based Hydrogels: Durable Conductive Biomaterials for Electroactive Tissues and Interfaces.

Light-cured conductive hydrogels have attracted immense interest in the regeneration of electroactive tissues and bioelectronic interfaces. Despite the unique properties of MXene (MX), its light-blocking effect in the range of 300-600 nm hinders the efficient cross-linking of photocurable hydrogels. In this study, we investigated the photo-cross-linking process of MX-gelatin methacrylate (GelMa) composites with different types of photoinitiators and MX concentrations to prepare biocompatible, injectable, conductive, and photocurable composite hydrogels. The examined photoinitiators were Eosin Y, Irgacure 2959 (Type I), and lithium phenyl-2,4,6-trimethylbenzoyl phosphinate (Type II). The light-blocking effect of MX strongly affected the thickness, pore structure, swelling ratio, degradation, and mechanical properties of the light-cured hydrogels. Uniform distribution of MX in the hydrogel matrix was achieved at concentrations up to 0.04 wt % but the film thickness and curing times varied depending on the type of photoinitiator. It was feasible to prepare thin films (0.5 mm) by employing Type I photoinitiators under a relatively long light irradiation (4-5 min) while thick films with centimeter sizes could be rapidly cured by using Type II photoinitiator (<60 s). The mechanical properties, including elastic modulus, toughness, and stress to break for the Type II hydrogels were significantly superior (up to 300%) to those of Type I hydrogels depending on the MX concentration. The swelling ratio was also remarkably higher (648-1274%). A conductivity of about 1 mS/cm was attained at 0.1 mg/mL MX for the composite hydrogel cured by the Type I photoinitiator. In vitro cytocompatibility assays determined that the hydrogels promoted cell viability, metabolic activity, and robust proliferation of C2C12 myoblasts, which indicated their potential to support muscle cell growth during myogenesis. The developed photocurable GelMa-MX hydrogels have the potential to serve as bioactive and conductive scaffolds to modulate cellular functions and for tissue-device interfacing.

Multilayered Mesoporous Composite Nanostructures for Highly Sensitive Label-Free Quantification of Cardiac Troponin-I.

Cardiac troponin-I (cTnI) is a well-known biomarker for the diagnosis and control of acute myocardial infarction in clinical practice. To improve the accuracy and reliability of cTnI electrochemical immunosensors, we propose a multilayer nanostructure consisting of Fe3O4-COOH labeled anti-cTnI monoclonal antibody (Fe3O4-COOH-Ab1) and anti-cTnI polyclonal antibody (Ab2) conjugated on Au-Ag nanoparticles (NPs) decorated on a metal-organic framework (Au-Ag@ZIF-67-Ab2). In this design, Fe3O4-COOH was used for separation of cTnI in specimens and signal amplification, hierarchical porous ZIF-67 extremely enhanced the specific surface area, and Au-Ag NPs synergically promoted the conductivity and sensitivity. They were additionally employed as an immobilization platform to enhance antibody loading. Electron microscopy images indicated that Ag-Au NPs with an average diameter of 1.9 ± 0.5 nm were uniformly decorated on plate-like ZIF-67 particles (with average size of 690 nm) without any agglomeration. Several electrochemical assays were implemented to precisely evaluate the immunosensor performance. The square wave voltammetry technique exhibited the best performance with a sensitivity of 0.98 mA mL cm-2 ng-1 and a detection limit of 0.047 pg mL-1 in the linear range of 0.04 to 8 ng mL-1.

Controlled biodegradation of magnesium alloy in physiological environment by metal organic framework nanocomposite coatings.

Magnesium-based implants (MBIs) have recently attracted great attention in bone regeneration due to elastic modulus similar to bone. Nevertheless, the degradation rate and hydrogen release of MBIs in the body have to be tackled for practical applications. In the present study, we present a metal-organic framework (MOF) nanoplates to reduce the degradation rate of AZ91 magnesium alloy. Zeolitic imidazolate frameworks (ZIF-8) with a specific surface area of 1789 m2 g-1 were prepared by solvothermal methods, and after dispersion in a chitosan solution (10% w/w), the suspension was electrospun on the surface of AZ91 alloy. Studying the degradation rate in simulated body fluid (SBF) by electrochemical analysis including potentiodynamic polarization and electrochemical impedance spectroscopy reveals that the degradation rate of the surface-modified implants decreases by ~ 80% as compared with the unmodified specimens. The reduced alkalization of the physiological environment and hydrogen release due to the implant degradation are shown. In vitro studies by fibroblasts and MG63 osteosarcoma cells exhibit improved cell adhesion and viability. The mechanisms behind the improved degradation resistance and enhanced bioactivity are presented and discussed. Surface modification of MBIs by MOF-chitosan coatings is a promising strategy to control the biodegradation of magnesium implants for bone regeneration.

Biomimetic nanoengineered scaffold for enhanced full-thickness cutaneous wound healing.

Wound healing is a complex process based on the coordinated signaling molecules and dynamic interactions between the engineered scaffold and newly formed tissue. So far, most of the engineered scaffolds used for the healing of full-thickness skin wounds do not mimic the natural extracellular matrix (ECM) complexity and therefore are not able to provide an appropriate niche for endogenous tissue regeneration [1]. To address this gap and to accelerate the wound healing process, we present biomimetic bilayer scaffolds compositing of gelatin nanofibers (GFS) and photocrosslinkable composite hydrogels loaded with epidermal growth factors (EGF). The nanofibers operate as the dermis layer, and EGF-loaded composite hydrogels acted as the epidermis matrix for the full-thickness wound healing application. The hydrogels are composed of gelatin metacryloyl (GelMA) modified with silicate nanoplatelets (Laponite). To overcome the challenges of transdermal delivery of EGF, including short half-life and lack of efficient formulation precise, controlled delivery was attained by immobilization of EGF on Laponite. It is shown that the addition of 1wt% silicate nanoplatelet increases the compressive modulus of the hydrogels by 170%. In vitro wound closure analysis also demonstrated improved adhesion of the scaffolds to the native tissue by 3.5 folds. Moreover, the tunable hemostatic ability of the scaffolds due to the negatively charged nanoplatelets is shown. In an established excisional full-thickness wound model, an enhanced wound closure (up to 93.1 ± 1.5%) after 14 days relative to controls (GFS and saline-treated groups) is demonstrated. The engineered adhesive and hemostatic scaffolds with sustained release of the growth factors have the potential to stimulate complete skin regeneration for full-thickness wound healing.

Nanoengineered shear-thinning and bioprintable hydrogel as a versatile platform for biomedical applications.

The development of bioinks based on shear-thinning and self-healing hydrogels has recently attracted significant attention for constructing complex three-dimensional physiological microenvironments. For extrusion-based bioprinting, it is challenging to provide high structural reliability and resolution of printed structures while protecting cells from shear forces during printing. Herein, we present shear-thinning and printable hydrogels based on silicate nanomaterials, laponite (LA), and glycosaminoglycan nanoparticles (GAGNPs) for bioprinting applications. Nanocomposite hydrogels (GLgels) were rapidly formed within seconds due to the interactions between the negatively charged groups of GAGNPs and the edges of LA. The shear-thinning behavior of the hydrogel protected encapsulated cells from aggressive shear stresses during bioprinting. The bioinks could be printed straightforwardly into shape-persistent and free-standing structures with high aspect ratios. Rheological studies demonstrated fast recovery of GLgels over multiple strain cycles. In vitro studies confirmed the ability of GLgels to support cell growth, proliferation, and spreading. In vitro osteogenic differentiation of pre-osteoblasts murine bone marrow stromal cells encapsulated inside the GLgels was also demonstrated through evaluation of ALP activity and calcium deposition. The subcutaneous implantation of the GLgel in rats confirmed its in vivo biocompatibility and biodegradability. The engineered shear-thinning hydrogel with osteoinductive characteristics can be used as a new bioink for 3D printing of constructs for bone tissue engineering applications.

Drug-eluting PCL/graphene oxide nanocomposite scaffolds for enhanced osteogenic differentiation of mesenchymal stem cells.

Recently, drug-eluting nanofibrous scaffolds have attracted a great attention to enhance the cell differentiation through biomimicking the extracellular matrix (ECM) in regenerative medicine. In this study, electrospun nanocomposite polycaprolactone (PCL)-based scaffolds containing synthesized graphene oxide (GO) nanosheets and osteogenic drugs, i.e. dexamethasone and simvastatin were fabricated. The physicochemical and surface properties of the scaffolds were investigated through FTIR, wettability, pH, and drug release studies. The cell viability, differentiation, and biomineralization were studied on mesenchymal stem cells (MSCs) by Alamar Blue, alkaline phosphatase (ALP) activity, and Alizarin Red-S staining, respectively. Uniformly distributed GO (thickness < 1 nm) in PCL nanofibers was observed by electron microscopy. It was revealed that the addition of GO and the drugs improved the hydrophilicity, cell viability, and osteogenic differentiation, in addition to pH changes, in comparison with PCL scaffolds. Despite the notable reduction in the cell viability, significant differentiation was revealed by ALP assay on PCL/GO-Dex scaffolds. Noteworthy, a twofold increase in the osteogenic differentiation was observed in comparison with the cells cultured in osteogenic differentiation medium, while a significant biomineralization was observed. The results of this study indicate the synergistic effect of GO and dexamethasone on improving osteogenic differentiation of drug-eluting nanocomposite scaffolds in bone tissue engineering applications.

The effect of laser frequency on roughness, microstructure, cell viability and attachment of Ti6Al4V alloy.

Titanium alloys are commonly used in orthopedic devices due to their good corrosion resistance, high specific strength and excellent biological response. The direct contact between the implant surface and the host tissue results in notable effect of surface properties such as surface topography on the biological responses. The aim of this study is to investigate the effect of frequency of pulsed Nd-YAG laser on Ti6Al4V alloy surface topography and its influence on the improvement of biocompatibility while other laser parameters kept constant. The range of applied frequency values were selected from 1 to 20 Hz. The range of surface roughness was found between 452 nm and 3.37 µm. The untreated sample and also samples with the highest and the lowest average surface roughness parameter were subjected to the further analyses. Characterization of the samples was performed with surface roughness tester, Scanning Electron Microscopy (SEM), and Atomic Force Microscopy (AFM). The high rate of melt and solidification during the laser treatment led to the martensite formation and consequently an increase about 12-25% in hardness. Furthermore, in vitro study was carried out using MG-63 osteoblast like cells. The analyses of cell viability for 3 culture times, cell morphology and cell spreading area revealed that sample with the highest average surface roughness parameter is more biocompatible. 10 Hz frequency was found as the optimum parameter which led to the highest surface roughness and thus the biocompatibility enhancement. In conclusion, the pulsed Nd-YAG laser with an optimum value of applied frequency can be utilized as an effective technique to improve the biological characteristics.

Sustainable drug release from highly porous and architecturally engineered composite scaffolds prepared by 3D printing.

Additive manufacturing techniques have evolved novel opportunities for the fabrication of highly porous composite scaffolds with well-controlled and interconnected pore structures which is notably important for tissue engineering. In this work, poly (ε-caprolactone) (PCL)-based composite scaffolds (average pore diameter of 450 µm and strut thickness of 400 µm) reinforced with 10 vol% bioactive glass particles (BG; ∼6 µm) or TiO2 nanoparticles (∼21 nm), containing different concentrations of tetracycline hydrochloride (TCH) as an antimicrobial agent, were prepared by 3D printing. In order to investigate the effect of fabrication process and scaffold geometry on the biocompatibility, drug release kinetics, and antibacterial activity, polymer and composite films (2D structures) were also prepared by solvent casting method. We demonstrate that even without any additional coating layer, sustainable release can be attained on highly porous scaffolds prepared by 3D printing due to chemical interactions between functional groups of TCH and the bioactive particles. Herein, the effect of TiO2 nanoparticles on the release rate is substantially more pronounced than BG particles. Nevertheless, agar well-diffusion and MTT assays determine better cellular viability and higher antibacterial effect for PCL/BG composite. Although all the drug-eluting composite scaffolds exhibit acceptable hemocompatibility, in vitro cellular and bacterial studies also determine that the maximum amount of TCH that can inhibit gram positive (Staphylococcus aureus) and gram negative (Escherichia coli) bacteria without cytotoxicity effect (≥95% viability) is 0.57 mg/ml. These findings may pave the way for designing structurally engineered composite scaffolds with sustainable drug release profile by additive manufacturing techniques for tissue engineering applications.

Core-sheath gelatin based electrospun nanofibers for dual delivery release of biomolecules and therapeutics.

Coaxial electrospinning with the ability to use simultaneously two separate solvents provides a promising strategy for drug delivery. Nevertheless, controlled release of hydrophilic and sensitive therapeutics from slow biodegradable polymers is still challenging. To address this gap, we fabricated core-sheath fibers for dual delivery of lysozyme, as a model protein, and phenytoin sodium as a small therapeutic molecule. The sheath was processed by a gelatin solution while the core fibers were fabricated from an aqueous gelatin/PVA solution. Microstructural studies by transmission and scanning electron microscopy reveal the formation of homogeneous core-sheath nanofibers with an outer and inner diameter of 180 ± 48 nm and 106 ± 30 nm, respectively. Thermal gravimetric analysis determines that the mass loss of the core-sheath fibers fall between the mass loss values of individual sheath and core fibers. Swelling studies indicate higher water absorption of the core-sheath mat compared to the separate sheath and core membranes. In vitro drug release studies in Phosphate Buffered Saline (PBS) determine sustained release of the therapeutics from the core-sheath structure. The release trails three stages including non-Fickian diffusion at the early stage followed by the Fickian diffusion mechanism. The present study shows a useful approach to design core-sheath nanofibrous membranes with controlled and programmable drug release profiles.

Biomimetic proteoglycan nanoparticles for growth factor immobilization and delivery.

The delivery of growth factors is often challenging due to their short half-life, low stability, and rapid deactivation. In native tissues, the sulfated residual of glycosaminoglycan (GAG) polymer chains of proteoglycans immobilizes growth factors through the proteoglycans'/proteins' complexation with nanoscale organization. These biological assemblies can influence growth factor-cell surface receptor interactions, cell differentiation, cell-cell signaling, and mechanical properties of the tissues. Here, we introduce a facile procedure to prepare novel biomimetic proteoglycan nanocarriers, based on naturally derived polymers, for the immobilization and controlled release of growth factors. We developed polyelectrolyte complex nanoparticles (PCNs) as growth factor nanocarriers, which mimic the dimensions, chemical composition, and growth factor immobilization of proteoglycans in native tissues. PCNs were prepared by a polymer-polymer pair reaction method and characterized for physicochemical properties. Fourier transform infrared spectroscopy (FTIR) analysis indicated that complexation occurred through electrostatic interactions. Transmission electron microscopy (TEM) results showed that the nanocarriers had a diameter of 60 ± 11 nm and 91 ± 33 nm for dermatan sulfate sodium salt-poly-l-lysine (DS-PLL) and gum tragacanth-poly-l-lysine (GT-PLL) complexes, respectively. The colloidal nanoparticles were stable due to their negative zeta potential, i.e.-25 ± 4 mV for DS-PLL and -18 ± 3.5 mV for GT-PLL. Cytocompatibility of PCNs in contact with human bone marrow stromal cells (HS-5) was confirmed through a live/dead assay and metabolic activity measurement. In addition, vascular endothelial growth factor (VEGF) was used to evaluate the ability of PCNs to stabilize growth factors. The capability of PCNs to preserve VEGF activity for up to 21 days was confirmed by analyzing the metabolic and mitogenic characteristics of human umbilical vein endothelial cells (HUVECs). Our results demonstrated the potential applications of these nanoparticles in therapeutic delivery for tissue regeneration applications.

Fabrication of hierarchically porous silk fibroin-bioactive glass composite scaffold via indirect 3D printing: Effect of particle size on physico-mechanical properties and in vitro cellular behavior.

In order to regenerate bone defects, bioactive hierarchically scaffolds play a key role due to their multilevel porous structure, high surface area, enhanced nutrient transport and diffusion. In this study, novel hierarchically porous silk fibroin (SF) and silk fibroin-bioactive glass (SF-BG) composite were fabricated with controlled architecture and interconnected structure, by combining indirect three-dimensional (3D) inkjet printing and freeze-drying methods. Further, the effect of 45S5 Bioactive glass particles of different sizes (<100 nm and 6 µm) on mechanical strength and cell behavior was investigated. The results demonstrated that the hierarchical structure in this scaffold was composed of two levels of pores in the order of 500-600 µm and 10-50 µm. The prepared SF-BG composite scaffolds utilized by nano and micro particles possessed mechanical properties with a compressive strength of 0.94 and 1.2 MPa, respectively, in dry conditions. In a wet condition, the hierarchically porous scaffolds did not exhibit any fluctuation after compression load cell and were incredibly flexible, with excellent mechanical stability. The SF-BG composite scaffold with nanoparticles presented a significant 50% increase in attachment of human bone marrow stem cells in comparison with SF and SF-BG scaffold with microparticles. Moreover, SF-BG scaffolds promoted alkaline phosphatase activity as compared to SF scaffolds without BG particles on day 14. In brief, the 3D porous silk fibroin-based composites containing BG nanoparticles with excellent mechanical properties are promising scaffolds for bone tissue regeneration in high load-bearing applications.

Modification of bacterial cellulose/keratin nanofibrous mats by a tragacanth gum-conjugated hydrogel for wound healing.

To enhance physicomechanical properties and bioactivity of fibrous membranes for wound dressing and tissue engineering applications, novel composite scaffolds consisting of fibrous mats and thermosensitive hydrogel particles were prepared by concurrent electrospinning and electrospraying technique. The composite scaffolds were composed of keratin/bacterial cellulose fibers (150 ±â€¯43 nm) which are hybridized with hydrogel particles (500 nm to 2 µm) based on nonionic triblock copolymers conjugated with Tragacanth gum (TG). FTIR and H-NMR studies indicated ester reactions between carboxylated copolymers and TG through carbodiimide crosslinker chemistry. The hydrogel particles were uniformly embedded into fibrous network at fiber junctions without changing its porous structure and the fiber diameter. Modification of the fibers with the hydrogel nanoparticles significantly improved the hydrophilicity (~23%), module of elasticity (~31%), tensile strength (~35%), and ductility (~23%) of the electrospun scaffold. In vitro culturing of the mats with L929 fibroblast cells determined the biocompatibility of the fibrous composite along with improved cell adhesion and proliferation.

Preparation of liposomal doxorubicin-graphene nanosheet and evaluation of its in vitro anti-cancer effects.

In recent years there has been much interest in development of multifunctional drug delivery systems. In this work, liposomes that contain doxorubicin (Dox), a potent anticancer drug, and graphene nanosheets (GNS) were prepared. The GNSs have excellent optical properties, such as photoluminescence which enables tracking of the liposomes, high absorption in ultra violet region of electromagnetic spectrum which can be exploited in photodynamic and photothermal therapy, and low toxicity to mammalian cells. Nanoliposomes were prepared using the thin film hydration method. Dox and GNSs were loaded to the liposomes during the hydration of the lipid film. Liposomes were characterized and the profile of in vitro drug release, cellular uptake, and cytotoxicity of the prepared liposomes on MCF-7 cells were determined. Despite the earlier reports, the liposomes have kept their spherical structures in the presence of GNSs. The cytotoxicity of liposomal Dox and GNSs were shown to be higher than the free forms of them. Novel nanoliposomes that contain GNSs have provided a multi-functional system with the potential of tracking, photodynamic and photothermal therapy. Further improvements of this versatile nanosystem would be promising for treatment of cancer.

Development of chitosan coated calcium-alginate nanocapsules for oral delivery of liraglutide to diabetic patients.

Chitosan coated calcium-alginate nanocapsules were developed for oral sustained delivery of liraglutide. The effect of coating components including sodium alginate, calcium chloride, and chitosan concentrations on the particle size was studied based on response surface methodology. The beads were characterized by dynamic light scattering, scanning and transmission electron microscopy as well as Fourier transform infrared spectroscopy. It was shown that the diameter of the formed beads was most dependent on the encapsulation technique and alginate concentration. SEM revealed spherical and smooth particles of up to 100 nm diameter for the optimum composition of alginate 0.5%, chitosan 0.5% and calcium chloride 0.5% in the volume ratio of 3:1:1. The resulting bead formulation had a loading efficiency of 92.5% and loading capacity of 54.16%. The nanocapsules exhibited stability of 92.4% and 72.3% over freeze drying and subsequent 60 days storage at 4 °C, respectively. In-vitro release studies in simulated gastrointestinal conditions were carried out in a sequential technique and the amount of drug release was found to be 59.1% after 6 h. The results of this study demonstrated that chitosan coated calcium-alginate nanocapsules hold promise as a potential natural biodegradable polymer-based oral carrier of liraglutide for better management of diabetes.

Sustained release of sodium deoxycholate from PLGA-PEG-PLGA thermosensitive polymer.

Delivery of the drugs to the target tissue and reducing their side effects on surrounding tissues is still a significant challenge for pharmaceutical scientists. The aim of this study was to investigate the suitability of PLGA-PEG-PLGA triblock copolymer as a matrix material for a sustained-release system of sodium deoxycholate (NaDC). The copolymer was synthesized by ring-opening polymerization reaction, using microwave irradiation and characterized by different techniques. It was shown that the introduction of NaDC to the PLGA-PEG-PLGA copolymer did not influence its inherent sol-gel transition behaviour, but increased the sol-gel transition. The results showed the appropriate NaDC/polymer interaction and the formation of NaDC/polymer-mixed micelle. The sustained release of NaDC from the copolymer lasted for 2 days. This release can be attributed to the formation of NaDC/polymer-mixed micelles and trapping NaDC in the copolymer matrix. The cytolytic efficacy of NaDC-loaded copolymer and sustained release of NaDC were investigated on human adipocytes. Overall a sustained-release formulation for NaDC can be used to study localized fat dissolution.

Dual-Sensitive Hydrogel Nanoparticles Based on Conjugated Thermoresponsive Copolymers and Protein Filaments for Triggerable Drug Delivery.

In this study, novel hydrogel nanoparticles with dual triggerable release properties based on fibrous structural proteins (keratin) and thermoresponsive copolymers (Pluronic) are introduced. Nanoparticles were used for curcumin delivery as effective and safe anticancer agents, the hydrophobicity of which has limited their clinical applications. A drug was loaded into hydrogel nanoparticles by a single-step nanoprecipitation method. The drug-loaded nanoparticles had an average diameter of 165 and 66 nm at 25 and 37 °C, respectively. It was shown that the drug loading efficiency could be enhanced through crosslinking of the disulfide bonds in keratin. Crosslinking provided a targeted release profile under reductive conditions using an in vivo agent, glutathione (GSH), or in the presence of trypsin. Cytocompatibility assay using HeLa and L929 fibroblast cells exhibited no adverse effect of nanoparticles on cell viability up to 1 mg/mL. Besides, the green fluorescence of curcumin confirmed the uptake of drug-loaded nanoparticles by cancer cells. The redox and temperature-sensitive nanoparticles are potentially useable for the efficient delivery of hydrophobic drugs to targeted regions having a triggerable release profile.

Biochemical mechanisms of dose-dependent cytotoxicity and ROS-mediated apoptosis induced by lead sulfide/graphene oxide quantum dots for potential bioimaging applications.

Colloidal quantum dots (CQD) have attracted considerable attention for biomedical diagnosis and imaging as well as biochemical analysis and stem cell tracking. In this study, quasi core/shell lead sulfide/reduced graphene oxide CQD with near infrared emission (1100 nm) were prepared for potential bioimaging applications. The nanocrystals had an average diameter of ~4 nm, a hydrodynamic size of ~8 nm, and a high quantum efficiency of 28%. Toxicity assay of the hybrid CQD in the cultured human mononuclear blood cells does not show cytotoxicity up to 200 µg/ml. At high concentrations, damage to mitochondrial activity and mitochondrial membrane potential (MMP) due to the formation of uncontrollable amounts of intracellular oxygen radicals (ROS) was observed. Cell membrane and Lysosome damage or a transition in mitochondrial permeability were also noticed. Understanding of cell-nanoparticle interaction at the molecular level is useful for the development of new fluorophores for biomedical imaging.

Enhanced cell attachment and hemocompatibility of titanium by nanoscale surface modification through severe plastic integration of magnesium-rich islands and porosification.

Besides the wide applications of titanium and its alloys for orthopedic and biomedical implants, the biocompatible nature of titanium has emerged various surface modification techniques to enhance its bioactivity and osteointegration with living tissues. In this work, we present a new procedure for nanoscale surface modification of titanium implants by integration of magnesium-rich islands combined with controlled formation of pores and refinement of the surface grain structure. Through severe plastic deformation of the titanium surface with fine magnesium hydride powder, Mg-rich islands with varying sizes ranging from 100 nm to 1000 nm can be integrated inside a thin surface layer (100-500 µm) of the implant. Selective etching of the surface forms a fine structure of surface pores which their average size varies in the range of 200-500 nm depending on the processing condition. In vitro biocompatibility and hemocompatibility assays show that the Mg-rich islands and the induced surface pores significantly enhance cell attachment and biocompatibility without an adverse effect on the cell viability. Therefore, severe plastic integration of Mg-rich islands on titanium surface accompanying with porosification is a new and promising procedure with high potential for nanoscale modification of biomedical implants.