Fullerol-reinforced antioxidantive 3D-printed bredigite scaffold for accelerating bone healing.

Reactive oxygen species play a vital role in tissue repair, and nonequilibrium of redox homeostasis around bone defect can compromise osteogenesis. However, insufficient antioxidant capacity and weak osteogenic performance remain major obstacles for bone scaffold materials. Herein, integrating the mussel-inspired polydopamine (PDA) coating and 3D printing technologies, we utilized the merits of both osteogenic bredigite and antioxidative fullerol to construct 3D-printed porous, biodegradable acid-buffering, reactive oxygen species (ROS) -scavenging and robust osteogenic bio-scaffold (denoted "FPBS") for in situ bone defect restoration under oxidative stress microenvironment. Initially, fullerol nanoparticles were attached to the surface of the bredigite scaffold via covalently inter-crosslinking with PDA. Upon injury, extracellular ROS capturing triggered the oxidative degradation of PDA, releasing fullerol nanoparticles to enter into cells for further intracellular ROS scavenging. In vitro, FPBS had good biocompatibility and excellent antioxidative capability. Furthermore, FPBS promoted the osteogenesis of stem cells with significant elevation of osteogenic markers. Finally, in vivo implantation of FPBS remarkably enhanced new bone formation in a rat critical calvarial defect model. Overall, with amelioration of the ROS microenvironment of injured tissue and enhancement of osteogenic differentiation of stem cells simultaneously, FPBS may hold great potential towards bone defect repair.

Asymmetric and Skin-Mimicking Hydrogels with Wide Temperature Tolerance and Superior Elasticity for High-Performance Strain Sensors.

Wide temperature tolerance and superior mechanical properties are highly required for composite hydrogels in electronic applications such as electronic skins and soft robotics. In this work, a unique polyacrylamide-based and double-network hydrogel system is designed and fabricated by introducing graphene oxide and glycerol to improve mechanical properties as well as antifreezing and antiheating properties. Maximum stress of the graphene oxide-incorporated hydrogel increases rapidly to 500.0 kPa which is much higher than that of polymetric acrylamide/carboxymethylcellulose sodium hydrogel (281.7 kPa), probably due to the inhibition from graphene oxide in generation and propagation of cracks. With constantly adding glycerol, total elongation and antifreezing and heating properties of the composite hydrogels increase gradually. Especially, sample with 20 vol % of glycerol not only shows stable conductivity and wide temperature tolerance (-50 to 50 °C) but also has ideal strength-toughness match (597.6 kPa and 1263.4%), suggesting that synergistic effect of different layers in the asymmetric structure plays an active role in improvement of mechanical properties.

Engineered and Durable Antimicrobial Polymer via Controllable Immobilization of Ionic Liquids onto the Poly(lactic acid) Chains.

Nowadays, the development of effective modification methods for PLA has gained significant interest because of the wide application of antimicrobial PLA materials in the medical progress. Herein, the ionic liquid (IL) 1-vinyl-3-butylimidazolium bis(trifluoromethylsulfonyl)imide, has been grafted onto the PLA chains successfully in the PLA/IL blending films via electron beam (EB) radiation for the miscibility between PLA and IL. It was found that the existence of IL in the PLA matrix can significantly improve the chemical stability under EB radiation. The Mn of PLA-g-IL copolymer did not change obviously but was just decreased from 6.80 × 104 g/mol to 5.20 × 104 g/mol after radiation with 10 kGy. The obtained PLA-g-IL copolymers showed excellent filament forming property during electrospinning process. The spindle structure on the nanofibers can be completely eliminated after feeding only 0.5 wt % ILs for the improvement of ionic conductivity. Specially, the prepared PLA-g-IL nonwovens exhibited outstanding and durable antimicrobial activity for the enrichment of immobilized ILs on the nanofiber surface. This work provides a feasible strategy to realize the modification of functional ILs onto PLA chains with low EB radiation doses, which may have huge potential application in the medical and packaging industry.

Dual-Stimuli-Responsive and Anti-Freezing Conductive Ionic Hydrogels for Smart Wearable Devices and Optical Display Devices.

Stimuli-responsive hydrogels are a class of important materials for the preparation of flexible sensors, but the development of UV/stress dual-responsive ion-conductive hydrogels with excellent tunability for wearable devices remains a major challenge. In this study, a dual-responsive multifunctional ion-conductive hydrogel (PVA-GEL-GL-Mo7) with high tensile strength, good stretchability, outstanding flexibility, and stability is successfully fabricated. The prepared hydrogel has an excellent tensile strength of 2.2 MPa, high tenacity of 5.26 MJ/m3, favorable extensibility (522%), and high transparency of 90%. Importantly, the hydrogels have dual responsiveness to UV light and stress, allowing it to be used as a wearable device while responding differently to the UV intensity of different outdoor environments (hydrogels can show different levels of color when exposed to different light intensities of UV light) and can remain flexible at -50 and 85 °C (sensing at both -25 and 85 °C). Therefore, the hydrogels developed in this study have good prospects in different applications, such as flexible wearable devices, duplicate paper, and dual-responsive interactive devices.

Osteoimmunomodulation role of exosomes derived from immune cells on osseointegration.

Despite the high success rate of biomedical implants adopted clinically, implant failures caused by aseptic loosening still raise the risk of secondary surgery and a substantial economic burden to patients. Improving the stable combination between the implant and the host bone tissue, achieving fast and high-quality osseointegration can effectively reduce the probability of aseptic loosening. Accumulating studies have shown that the osteoimmunomodulation mediated by immune cells mainly dominated by macrophages plays a pivotal role in osseointegration by releasing active factors to improve the inflammatory microenvironment. However, the mechanism by which osteoimmunomodulation mediates osseointegration remains unclear. Recent studies have revealed that exosomes released by macrophages play a central role in mediating osteoimmunomodulation. The exosomes can be internalized by various cells participating in de novo bone formation, such as endothelial cells and osteoblasts, to intervene in the osseointegration robustly. Therefore, macrophage-derived exosomes with multifunctionality are expected to significantly improve the osseointegration microenvironment, which is promising in reducing the occurrence of aseptic loosening. Based on this, this review summarizes recent studies on the effects of exosomes derived from the immune cells on osseointegration, aiming to provide a theoretical foundation for improving the clinical success rate of biomedical implants and achieving high-quality and high-efficiency osseointegration.

Construction of carbon-based flame retardant composite with reinforced and toughened property and its application in polylactic acid.

To simultaneously improve the flame retardancy, strength and toughness of polylactic acid (PLA) fibers, a composite flame retardant CNTs-H-C was prepared with carbon nanotubes (CNTs) as the core, hexachlorocyclotriphosphazene as linker, and chitosan grafted on the surface. The prepared CNTs-H-C was introduced into a PLA matrix to obtain CNTs-H-C/PLA composites and fibers via a melt-blending method. The morphology, structure, flame retardant properties and mechanical properties were thoroughly characterized, and the flame retardant mechanism was studied. Results showed that the prepared CNTs-H-C displayed a nanotube-like morphology with good compatibility and dispersion in the PLA matrix. After blending with PLA, CNTs-H-C/PLA composites exhibited outstanding flame retardancy with limiting oxygen index (LOI) increasing from 20.0% to 27.3%, UL94 rating reaching V-0. More importantly, the introduction of CNTs-H-C did not affect the spinnability of PLA. Compared with pure PLA fibers, the LOI of CNTs-H-C/PLA fibers with a CNTs-H-C content of 1.0 wt% increased by 32.5%, and meanwhile the breaking strength and elongation increased by 28.2% and 30.4%, respectively. Mechanism study revealed that CNTs-H-C/PLA possessed a typical condensed phase flame retardancy mechanism. In short, we have developed a CNT-based composite flame retardant with reinforced and toughened properties for the PLA matrix. The prepared CNTs-H-C showed great potential in polymer flame retardancy and mechanical enhancement.

One-Step Preparation of Adhesive Composite Hydrogels through Fast and Simultaneous In Situ Formation of Silver Nanoparticles and Crosslinking.

In this study, a series of gelatin/silver nanoparticles (AgNPs) composite hydrogels are prepared for the first time through the facile in situ formation of AgNPs. AgNPs, which are formed by reducing Ag+ using dopamine-conjugated gelatins. These can simultaneously crosslink gelatin molecules, thus generating three-dimentional and porous hydrogels. The gelation time and pore sizes of these composite hydrogels can be controlled by controlling the feeding concentration of AgNO3 and weight content of gelatin in water, respectively. The feeding concentration of AgNO3 also has an effect on the equilibrium swelling ratio of the hydrogels. Moreover, these composite hydrogels, with a controllable gelation time and in situ forming ability, exhibit good adhesive properties and can be used as drug-release depots.

Excellent rate capability supercapacitor based on a free-standing PEDOT:PSS film enabled by the hydrothermal method.

For the first time, herein, the hydrothermal method with H2SO4 as the solvent is introduced to enhance the rate capability of free-standing pristine PEDOT:PSS films. The film with a record conductivity of 3188 S cm-1 displays a rectangular characteristic at an ultrahigh scan rate of 1300 mV s-1 and a stable specific capacitance of 110 F cm-3 from 0.1 to 100 A cm-3, with a capacitance retention of up to 94.8%. The flexible supercapacitor based on the films delivers a comparable energy density of 2.96 mW h cm-3 even at a high power density of 36 685 mW cm-3. This study provides an effective method to prepare PEDOT:PSS films with outstanding electrochemical properties and potentially expand its applications in flexible devices.

Investigation on Tribological and Thermo-Mechanical Properties of Ti3C2 Nanosheets/Epoxy Nanocomposites.

In this study, two-dimensional Ti3C2 nanosheets were employed to improve the tribological and thermo-mechanical properties of epoxy resin. The Ti3C2 nanosheets were prepared by ultrasound-assisted delamination of multilayered Ti3C2 microparticles, and the Ti3C2 nanosheets/epoxy (Ti3C2/epoxy) nanocomposites were fabricated through physical blending and curing reaction. Scanning electron microscopy results showed that the Ti3C2 nanosheets were dispersed uniformly in the epoxy matrix. Tribological test results showed that the wear rate of Ti3C2/epoxy nanocomposites was only 6.61 × 10-14 m3/(N m) at a 1% mass fraction, which was reduced by 72.1% compared to that of neat epoxy. The morphologies of worn surfaces revealed that the wear form of Ti3C2/epoxy nanocomposites transformed gradually from fatigue wear to adhesive wear with the increase of mass fraction of Ti3C2 nanosheets. Moreover, the results of thermo-mechanical properties indicated that incorporation of Ti3C2 nanosheets effectively improved the storage modulus and glass-transition temperature (T g) of epoxy resin. This work provides guidance for improving the tribological and thermo-mechanical properties of epoxy resin.

Efficient co-delivery of microRNA 21 inhibitor and doxorubicin to cancer cells using core-shell tecto dendrimers formed via supramolecular host-guest assembly.

Development of versatile and powerful nanoplatforms for efficient therapeutic delivery represents a major topic for current nanomedicine. Herein, we present the development of core-shell tecto dendrimers (CSTDs) for co-delivery of a therapeutic gene and drug for enhanced anticancer therapy applications. In this work, CSTDs were first prepared via supramolecular recognition of ß-cyclodextrin (CD)-decorated generation 5 (G5) poly(amidoamine) (PAMAM) dendrimers as cores and adamantane (Ad)-functionalized G3 PAMAM dendrimers as shell components. The formed CSTDs with each G5 dendrimer surrounded with 4.2 G3 dendrimers were evaluated as a gene vector for delivery of plasmid DNA encoding enhanced green fluorescent protein as well as microRNA 21 inhibitor (miR 21i). We show that under an appropriate N/P ratio, the CSTDs enable effective transfection of both genetic materials to cancer cells. In particular, the transfection of miR 21i led to the inhibition of cancer cell migration, decreased miR 21 gene expression, and the effective regulation of the target genes and proteins (e.g., PTEN, PDCD4, p53, and Caspase-3). Furthermore, we revealed that the CSTDs were able to co-deliver miR 21i and an anticancer drug doxorubicin, leading to enhanced therapeutic efficacy to cancer cells in vitro. Our findings imply that the developed CSTDs could be adopted as a versatile platform for effective co-delivery of different therapeutic components for enhanced anticancer therapy applications.

Design of DNA Aptamer-Functionalized Magnetic Short Nanofibers for Efficient Capture and Release of Circulating Tumor Cells.

The isolation of viable circulating tumor cells (CTCs) from blood is of paramount significance for early stage detection and individualized therapy of cancer. Currently, CTCs isolated by conventional magnetic separation methods are tightly coated with magnetic materials even after attempted coating removal treatments, which is not conducive for subsequent analysis of CTCs. Herein, we developed DNA aptamer-functionalized magnetic short nanofibers (aptamer-MSNFs) for efficient capture and release of CTCs. In our work, polyethylenimine (PEI)-stabilized Fe3O4 nanoparticles with a mean diameter of 22.6 nm were first synthesized and encapsulated within PEI/poly(vinyl alcohol) nanofibers via a blended electrospinning process. After a homogenization treatment to acquire the MSNFs, surface conjugation of the DNA aptamer was performed through thiol-maleimide coupling. The formed aptamer-MSNFs, with a mean diameter of 350 nm and an average length of 9.6 µm, display a saturated magnetization of 12.3 emu g-1, are capable of specifically capturing cancer cells with an efficiency of 87%, and enable the nondestructive release of cancer cells with a release efficiency of 91% after nuclease treatment. In particular, the prepared aptamer-MSNFs displayed a significantly higher release efficiency than commercial magnetic beads. The designed aptamer-MSNFs may hold great promise for CTC capture and release as well as for other cell sorting applications.

Ultrasmall iron oxide nanoparticles: synthesis, surface modification, assembly, and biomedical applications.

Ultrasmall iron oxide nanoparticles (USIO NPs) with a size <5nm are a class of emerging nanomaterials. As a result of their intrinsic drawbacks related to poor colloidal stability, low r1 relaxivity, and lack of functionality, various strategies have been adopted to synthesize USIO NPs with controllable sizes, to surface modify the particles with polymers, and to assemble them in combination with other nanoscale platforms. Here, we review recent progresses in the synthesis, surface modification, and self-assembly of USIO NPs to address key issues in their biomedical application in the field of cancer diagnosis and therapy, in particular magnetic resonance (MR) imaging, dual-modal or multimodal imaging, drug delivery, and theranostics.

Specific capture and release of circulating tumor cells using a multifunctional nanofiber-integrated microfluidic chip.

AIM: To develop a multifunctional nanofibrous mat-embedded microfluidic chip system for specific capture and intact release of circulating tumor cells. MATERIALS & METHODS: Electrospun polyethylenimine/polyvinyl alcohol nanofibers were functionalized with zwitterions to reduce the nonspecific adhesion of blood cells, followed by modification with arginine-glycine-aspartic acid peptide via an acid-sensitive benzoic imine bond. RESULTS: The nanofiber-embedded microchip can be applied for capturing various types of cancer cells and circulating tumor cells with high efficiency and considerable purity. The captured cancer cells can be released from the nanofibrous substrates within 30 min. CONCLUSION: The developed multifunctional nanofiber-embedded microfluidic chip may have a great potential for clinical applications.

Electrospun PEGylated PLGA nanofibers for drug encapsulation and release.

We report the fabrication of electrospun nanofibers of polyethylene glycol (PEG)-modified poly (lactic-co-glycolic acid) (PLGA) with a fast release profile for biomedical applications. In this work, PLGA was first covalently modified with methoxy poly (ethylene glycol) amine (mPEG-NH2). The formed PEGylated PLGA (PLGA-PEG) was then mixed with a model drug amoxicillin (AMX) for subsequent fabrication of drug-loaded electrospun nanofibers. The synthesized PLGA-PEG conjugate and the formed drug-loaded PLGA-PEG nanofibers were characterized using different techniques. We show that the modification of PEG does not lead to an appreciable change in the uniform and smooth morphology of PLGA nanofibers. Importantly, the PEGylation modification affords a faster release profile of the encapsulated drug than pure PLGA nanofibers without PEGylation, which may be ascribed to the improved hydrophilicity of the PLGA-PEG polymer. Furthermore, antibacterial activity assay data reveal that the drug-loaded PLGA-PEG nanofibers are able to inhibit the growth of a model bacterium S. aureus. Finally, the hemocompatibility of the drug-loaded PLGA-PEG nanofibers was evaluated by hemolysis and anticoagulant assays, and the cytocompatibility of the fibers was confirmed by cell viability assay and cell morphology observation. We show that the formed drug-loaded PLGA-PEG nanofibers have an excellent hemocompatibility and cytocompatibility. The developed electrospun PLGA-PEG nanofibers may find various applications in the fields of tissue engineering and pharmaceutical sciences.

A Microfluidic Chip Integrated with Hyaluronic Acid-Functionalized Electrospun Chitosan Nanofibers for Specific Capture and Nondestructive Release of CD44-Overexpressing Circulating Tumor Cells.

Detection of circulating tumor cells (CTCs) in peripheral blood is of paramount significance for early-stage cancer diagnosis, estimation of cancer development, and individualized cancer therapy. Herein, we report the development of hyaluronic acid (HA)-functionalized electrospun chitosan nanofiber (CNF)-integrated microfludic platform for highly specific capture and nondestructive release of CTCs. First, electrospun CNFs were formed and modified with zwitterion of carboxyl betaine acrylamide (CBAA) via Michael addition reaction and then targeting ligand HA through a disulfide bond. We show that the formed nanofibers still maintain the smooth fibrous morphology after sequential surface modifications, have a good hemocompatibility, and exhibit an excellent antifouling property due to the CBAA modification. After being embedded within a microfluidic chip, the fibrous mat can capture cancer cells (A549, a human lung cancer cell line) with an efficiency of 91% at a flow rate of 1.0 mL/h. Additionally, intact release of cancer cells is able to be achieved after treatment with glutathione for 40 min to have a release efficiency of 90%. Clinical applications show that 9 of 10 nonsmall-cell lung cancer patients and 5 of 5 breast cancer patients are diagnosed to have CTCs (1 to 18 CTCs per mL of blood). Our results suggest that the developed microfluidic system integrated with functionalized CNF mats may be employed for effective CTCs capture for clinical diagnosis of cancer.

Design of functional electrospun nanofibers for cancer cell capture applications.

Electrospun nanofibers possess an extremely large surface area to volume ratio, good biocompatibility, ability to mimic native extracellular matrix, and the advantages of easy preparation and surface functionalization. These properties enable them to be used as an ideal platform for cancer cell capture applications. This review reports some recent advances in the use of nanofibers for cancer cell capture applications, in particular, preparation and surface functionalization of nanofibers with targeting molecules, static capture of cancer cells using nanofibrous substrates, dynamic capture of cancer cells and circulating tumor cells using fiber-integrated microfluidic platforms, and strategies used to release the captured cancer cells. Some of the key developments are introduced and summarized in detail; future perspectives are also briefly discussed.