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The 18kt gold-based bulk glass-forming composition Au49Ag5.5Pd2.3Cu26.9Si16.3 is modified in order to reduce its fast surface tarnishing caused by internal oxidation of Si, partitioning and fast out-diffusion of Cu and Au. By partially substituting Cu by the species Ga or Sn, the formation of Si as primary crystalline phase is facilitated and a distinct increase of the liquidus temperature is observed. It is found that a reduction of the Si content recovers the glass-forming ability of the novel Ga/Sn-containing alloys, reflected by an increasing reduced glass transition temperature, Trg, and a decreasing driving force for crystallization. This strategy is used to reduce the amount of Cu and Si, which are responsible for the fast surface tarnishing. Corrosion studies of the novel alloys reveal that the Cu release into an artificial saliva test solution is up to eight times lower than that of the mother alloy and the corrosion depth in artificial saliva is drastically lowered by 50% for the Ga-bearing alloys and by 80% for the Sn-bearing alloys. Keywords: Bulk metallic glass, Gold, Corrosion, Alloy development, Jewelry application

The major challenge in photothermal therapy (PTT) is to develop nanocomposites that simultaneously exhibit bioimaging and PTT under a single near-infrared (NIR) irradiation with high therapeutic efficiency. Herein, we present a multifunctional nanocomposite synthesized by linking NaYF4:Yb3+,Er3+ upconversion nanoparticles (UCNPs) with gold nanorods (AuNR) to exhibit fluorescence labeling, local temperature sensing and photothermal functions simultaneously with a single NIR laser excitation. The AuNR-NaYF4:Yb3+,Er3+ nanocomposite particles displayed better photothermal properties compared with pure AuNRs or a blend of AuNRs and NaYF4:Yb3+,Er3+ UCNPs. The temperature-dependent upconversion luminescence (UCL) property was used to determine local temperature at the nanocomposite particles, which is useful for selecting appropriate irradiation dosage for PTT. The therapeutic performance of the nanocomposites in PTT for OML-1 oral cancer cells was determined. For cell labeling, we successfully labeled streptavidin-linked nanocomposite particles on the surface of OML-1 oral cancer using anti-human epidermal growth factor receptor 2 (anti-Her2) antibody. Finally, the nanocomposite particles caused exceptional destruction of cancer cells up to 70% dead cells under 976 nm laser irradiation for only one min at 0.3 W/cm2 which is below the maximal permissible exposure of human skin.

Many researchers working on the development of Dye-sensitized solar cells (DSCs) continue to focus on the synthesis of photoanode materials with high surface area, along with high light scattering ability to enhance light harvesting efficiency (LHE). On the other hand, dye packing density, which can also affect the LHE significantly, is often overlooked. Solvothermally synthesized anatase TiO2 nanoparticles (SANP) were obtained by a new and simple approach using a mixed solvent, ethanol and acetic acid. SANP were applied as a photoanodes material in DSCs using a metal-free organic dye (D149) or organometallic dye (N719) dyes. The dye loading (packing density) was examined in term of the isoelectric point (IEP) and the contribution of this, in addition to light scattering effects were shown to control the devices photovoltaic efficiency of the devices; specifically when compared with ones employing commercially available TiO2 nanoparticles (either transparent or a bilayer structure with a transparent layer and a scattering one). SANP photoanodes sensitized with D149 dye were found to be optimised at 10 µm, yielding photovoltaic conversion efficiencies of 6.9%, superior to for transparent or transparent + scattering films from the commercial source (5.6% and 5.9%, respectively). Further to this, an efficiency of 7.7% PCE was achieved using a SANP photoanode sensitized with N719 dye, with 7.2% seen for the transparent photoanode and 7.9% with a scattering layer. The high efficiencies of devices based on of SANP photoanode are attributed to the high dye loading capability in addition to good light scattering. A further point of interest is that even with the increased reactivity of the surface towards dye adsorption, we did not observe any significant increase in recombination with the redox mediator, presumably due to this increased dye loading providing better shielding.

In the present paper we discuss correlations between crystal structure and magnetic properties of epitaxial ε-Fe2O3 films grown on GaN. The large magnetocrystalline anisotropy and room temperature multiferroic properties of this exotic iron oxide polymorph, make it a perspective material for the development of low power consumption magnetic media storage devices. Extending our recent progress in PLD growth of ε-Fe2O3 on the surface of technologically important nitride semiconductors, we apply reciprocal space tomography by electron and x-ray diffraction to investigate the break of crystallographic symmetry occurring at the oxide-nitride interface resulting in the appearance of anisotropic crystallographic disorder in the sub-100 nm ε-Fe2O3 films. The orthorhombic-on-hexagonal nucleation scenario is shown responsible for the development of a peculiar columnar structure observed in ε-Fe2O3 by means of HRTEM and AFM. The complementary information on the direct and reciprocal space structure of the columnar ε-Fe2O3 films is obtained by various techniques and correlated to their magnetic properties. The peculiar temperature dependence of magnetization studied by the small-field magnetization derivative method and by neutron diffraction reveals the existence of a magnetic softening below 150 K, similar to the one observed earlier solely in nanoparticles. The magnetization reversal in ε-Fe2O3 films probed by X-ray magnetic circular dichroism is found different from the behavior of the bulk averaged magnetization measured by conventional magnetometry. The presented results fill the gap between the numerous studies performed on randomly oriented ε-Fe2O3 nanoparticles and much less frequent investigations of epitaxial epsilon ferrite films with lattice orientation fixed by the substrate.

The effect of Sc-microalloying and Y2O3 nano-particles on the microstructure and mechanical properties of as-cast Al-5.5Si alloy is studied by means of optical microscopy, transmission electron microscopy, hardness test and tensile test. The influence of annealing treatment on the microstructure and properties of the Al-Si alloys is also investigated as well. The results show that the addition of Sc and Y2O3 nano-particles could significantly improve the mechanical property of the Al-Si alloy. The ultimate tensile strength and yield strength of Al-Si-Sc/Y2O3 alloy are improved by around 45 and 71%, respectively, when compared to that of the Al-Si alloy. The effect of the nanosized particles (precipitated and added) on strengthening and deformation of Al-Si alloy is analyzed and discussed in detail. The results of annealing treatment indicate that the change in mechanical property of the Al-Si-Sc alloy during annealing treatment is mainly associated with the precipitation of the secondary Si phase.

We report the unique growth of nanofibers in silica and borosilicate glass using femtosecond laser radiation at 8 MHz repetition rate and a pulse width of 214 fs in air at atmospheric pressure. The nanofibers are grown perpendicular to the substrate surface from the molten material in laser-drilled microvias where they intertwine and bundle up above the surface. The fibers are few tens of nanometers in thickness and up to several millimeters in length. Further, it is found that at some places nanoparticles are attached to the fiber surface along its length. Nanofiber growth is explained by the process of nanojets formed in the molten liquid due to pressure gradient induced from the laser pulses and subsequently drawn into fibers by the intense plasma pressure. The attachment of nanoparticles is due to the condensation of vapor in the plasma.

Therapeutic approaches for musculoskeletal tissue regeneration commonly employ growth factors (GFs) to influence neighboring cells and promote migration, proliferation, or differentiation. Despite promising results in preclinical models, the use of inductive biomacromolecules has achieved limited success in translation to the clinic. The field has yet to sufficiently overcome substantial hurdles such as poor spatiotemporal control and supraphysiological dosages, which commonly result in detrimental side effects. Physiological presentation and retention of biomacromolecules is regulated by the extracellular matrix (ECM), which acts as a reservoir for GFs via electrostatic interactions. Advances in the manipulation of extracellular proteins, decellularized tissues, and synthetic ECM-mimetic applications across a range of biomaterials have increased the ability to direct the presentation of GFs. Successful application of biomaterial technologies utilizing ECM mimetics increases tissue regeneration without the reliance on supraphysiological doses of inductive biomacromolecules. This review describes recent strategies to manage GF presentation using ECM-mimetic substrates for the regeneration of bone, cartilage, and muscle., Graphical abstract Image 1, Highlights • The contribution of growth factors during endogenous formation and repair of bone, cartilage, and muscle is reviewed. • The application and challenges of growth factors in clinical applications is discussed. • Carriers for growth factors are described, with an emphasis on the native extracellular matrix (ECM) and its constituents. • Frontiers in growth factor delivery are highlighted.

Biodegradable elastomers are important emerging biomaterials for biomedical applications, particularly in the area of soft-tissue engineering in which scaffolds need to match the physicochemical properties of native tissues. Here, we report novel fast photocurable elastomers with readily tunable mechanical properties, surface wettability, and degradability. These elastomers are prepared by a 5-min UV-irradiation of thiol-ene reaction systems of glycerol tripentenoate (GTP; a triene) or the combination of GTP and 4-pentenyl 4-pentenoate (PP; a diene) with a carefully chosen series of di- or tri-thiols. In the subsequent application study, these elastomers were found to be capable of overcoming delamination of myotubes, a technical bottleneck limiting the in vitro growth of mature functional myofibers. The glycerol-based elastomers supported the proliferation of mouse and human myoblasts, as well as myogenic differentiation into contractile myotubes. More notably, while beating mouse myotubes detached from conventional tissue culture plates, they remain adherent on the elastomer surface. The results suggest that these elastomers as novel biomaterials may provide a promising platform for engineering functional soft tissues with potential applications in regenerative medicine or pharmacological testing., Graphical abstract Image 1, Highlights • Biocompatible elastomers are formed by thiol-ene UV-curing within 5 min. • Tunable wettability, mechanical properties, and degradability of the elastomers. • The elastomers remarkably promote myogenic differentiation of myoblasts. • Myotubes on the elastomers exhibit enhanced attachment and beating frequency.

Primary ovarian insufficiency (POI) is an ovarian dysfunction that affects more than 1 % of women and is characterized by hormone imbalances that afflict women before the age of 40. The typical perimenopausal symptoms result from abnormal levels of sex hormones, especially estrogen. The most prevalent treatment is hormone replacement therapy (HRT), which can relieve symptoms and improve quality of life. However, HRT cannot restore ovarian functions, including secretion, ovulation, and fertility. Recently, as part of a developing field of regenerative medicine, stem cell therapy has been proposed for the treatment of POI. Thus, we recapitulate the literature focusing on the use of stem cells and biomaterials for POI treatment, and sum up the underlying mechanisms of action. A thorough understanding of the work already done can aid in the development of guidelines for future translational applications and clinical trials that aim to cure POI by using regenerative medicine and biomedical engineering strategies., Graphical abstract Graphical abstract: Multiple sources of MSCs and their roles in improving ovarian functions. MSCs isolated from various kinds of tissues and organs, such as bone marrow, adipose tissue, placenta, endometrium, and umbilical cord have been used as treatments for POI to stimulate follicle growth and improve oocyte quality, ovulation, and fertility.Image 1, Highlights • This paper illustrates the in-vivo, in-vitro, and cell-free treatments for POI using stem cells and biomaterials. • We provide basic theories and suggestions for future research and clinical therapy translation. • This review can help researcher to develop guidelines on stem cells treating POI.

Developmental engineering strategy needs the biomimetic composites that can integrate the progenitor cells, biomaterial matrices and bioactive signals to mimic the natural bone healing process for faster healing and reconstruction of segmental bone defects. We prepared the gelatin-reduced graphene oxide (GOG) and constructed the composites that mimicked the procallus by combining the GOG with the photo-crosslinked gelatin hydrogel. The biological effects of the GOG-reinforced composites could induce the bi-differentiation of bone marrow stromal cells (BMSCs) for rapid bone repair. The proper ratio of GOG in the composites regulated the composites' mechanical properties to a suitable range for the adhesion and proliferation of BMSCs. Besides, the GOG-mediated bidirectional differentiation of BMSCs, including osteogenesis and angiogenesis, could be activated through Erk1/2 and AKT pathway. The methyl vanillate (MV) delivered by GOG also contributed to the bioactive signals of the biomimetic procallus through priming the osteogenesis of BMSCs. During the repair of the calvarial defect in vivo, the initial hypoxic condition due to GOG in the composites gradually transformed into a well-vasculature robust situation with the bi-differentiation of BMSCs, which mimicked the process of bone healing resulting in the rapid bone regeneration. As an inorganic constituent, GOG reinforced the organic photo-crosslinked gelatin hydrogel to form a double-phase biomimetic procallus, which provided the porous extracellular matrix microenvironment and bioactive signals for the bi-directional differentiation of BMSCs. These show a promised application of the bio-reduced graphene oxide in biomedicine with a developmental engineering strategy., Graphical abstract Image 1, Highlights • The gelatin-reduced graphene oxide (GOG) was used to reinforce the photo-crosslinked gelatin hydrogel. • The GOG reinforced composite hydrogel was constructed to mimic the procallus for bone regeneration. • The bi-differentiation of bone marrow stromal cells (BMSCs) could be induced by the composite hydrogel.

Severe ischemic stroke damages neuronal tissue, forming irregular-shaped stroke cavities devoid of supporting structure. Implanting biomaterials to provide structural and functional support is thought to favor ingrowth of regenerated neuronal networks. Injectable hydrogels capable of in situ gelation are often utilized for stroke repair, but challenged by incomplete gelation and imprecise control over end-macrostructure. Injectable shape-memory scaffolds might overcome these limitations, but are not explored for stroke repair. Here, we report an injectable, photoluminescent, carbon-nanotubes-doped sericin scaffold (CNTs-SS) with programmable shape-memory property. By adjusting CNTs' concentrations, CNTs-SS′ recovery dynamics can be mathematically calculated at the scale of seconds, and its shapes can be pre-designed to precisely match any irregular-shaped cavities. Using a preclinical stroke model, we show that CNTs-SS with the customized shape is successfully injected into the cavity and recovers its pre-designed shape to well fit the cavity. Notably, CNTs-SS’ near-infrared photoluminescence enables non-invasive, real-time tracking after in vivo implantation. Moreover, as a cell carrier, CNTs-SS not only deliver bone marrow mesenchymal stem cells (BMSCs) into brain tissues, but also functionally promote their neuronal differentiation. Together, we for the first time demonstrate the feasibility of applying injectable shape-memory scaffolds for stroke repair, paving the way for personalized stroke repair., Graphical abstract Image 1, Highlights • A customized stroke cavity repairing strategy using preformed sericin-based scaffold with programmable shape-memory properties. • Injectability facilitates its' in vivo delivery and minimizes implantation injury. • Embedded CNTs endowing this biomaterial neuro-differentiation-promoting activity.

The tumor development and metastasis are closely related to the structure and function of the tumor microenvironment (TME). Recently, TME modulation strategies have attracted much attention in cancer immunotherapy. Despite the preliminary success of immunotherapeutic agents, their therapeutic effects have been restricted by the limited retention time of drugs in TME. Compared with traditional delivery systems, nanoparticles with unique physical properties and elaborate design can efficiently penetrate TME and specifically deliver to the major components in TME. In this review, we briefly introduce the substitutes of TME including dendritic cells, macrophages, fibroblasts, tumor vasculature, tumor-draining lymph nodes and hypoxic state, then review various nanoparticles targeting these components and their applications in tumor therapy. In addition, nanoparticles could be combined with other therapies, including chemotherapy, radiotherapy, and photodynamic therapy, however, the nanoplatform delivery system may not be effective in all types of tumors due to the heterogeneity of different tumors and individuals. The changes of TME at various stages during tumor development are required to be further elucidated so that more individualized nanoplatforms could be designed., Graphical abstract Image 1, Highlights • In responsive to the changes in TME, nanoparticles target tumor microenvironment and enhance the therapeutic effect. • Nanoparticles modulate the activation and maturation of DC. • Nanoparticles could reprogram polarization of TAM and relieve hypoxia. • Nanoparticles could transfer the immunosuppressive TME to immunosupportive.

Sea squirt, as a highly invasive species and main biofouling source in marine aquaculture, has seriously threatened the biodiversity and aquaculture economy. On the other hand, a conductive biomaterial with excellent biocompatibility, and appropriate mechanical property from renewable resources is urgently required for tissue engineering patches. To meet these targets, we presented a novel and robust strategy for sustainable development aiming at the marine pollution via recycling and upgrading the waste biomass-sea squirts and serving as a renewable resource for functional bio-scaffold patch in tissue engineering. We firstly demonstrated that the tunic cellulose derived natural self-conductive scaffolds successfully served as functional cardiac patches, which significantly promote the maturation and spontaneous contraction of cardiomyocytes both in vitro and enhance cardiac function of MI rats in vivo. We believe this novel, feasible and “Trash to Treasure” strategy to gain cardiac patches via recycling the waste biomass must be promising and beneficial for marine environmental bio-pollution issue and sustainable development considering the large-scale consumption potential for tissue engineering and other applications., Graphical abstract Image 1, Highlights • Fouling sea squirts used as scaffold materials can effectively solve the pollution problem of marine aquaculture. • The natural electrical conductivity of the sea squirts derived scaffold is similar to that of natural myocardial tissue. • Cellulose scaffold from sea squirts has a good orientation, and its structure is similar to natural myocardial tissue. • Sea squirts cellulose derived natural self-conductive scaffolds were successfully served as the functional cardiac patches.

The mechanical environment and anisotropic structure of the heart modulate cardiac function at the cellular, tissue and organ levels. During myocardial infarction (MI) and subsequent healing, however, this landscape changes significantly. In order to engineer cardiac biomaterials with the appropriate properties to enhance function after MI, the changes in the myocardium induced by MI must be clearly identified. In this review, we focus on the mechanical and structural properties of the healthy and infarcted myocardium in order to gain insight about the environment in which biomaterial-based cardiac therapies are expected to perform and the functional deficiencies caused by MI that the therapy must address. From this understanding, we discuss epicardial therapies for MI inspired by the mechanics and anisotropy of the heart focusing on passive devices, which feature a biomaterials approach, and active devices, which feature robotic and cellular components. Through this review, a detailed analysis is provided in order to inspire further development and translation of epicardial therapies for MI., Graphical abstract In this paper, we review cardiac mechanostructure and epicardial devices for cardiac support and relate their design to biological remodeling and heart function after myocardial infarction. Reprinted from Ref. [1] with permission from Elsevier (left panel); reproduced with permission of SynCardia, © 2020 (middle panel). All rights reserved; reprinted from Ref. [2] with permission (right panel); the publisher for this copyrighted material is Mary Ann Liebert, Inc. publishers.Image 1, Highlights • Mechanics and structure, two key factors in cardiac function, significantly change during MI and subseqent healing. • Epicardial restraint devices have been explored clinically as a way to mechanically reinforce the ventricular wall post- MI. • Current research demonstrates the potential of epicardial devices to preserve heart function post-MI.

Trans-catheter arterial embolization (TAE) plays an important role in treating various diseases. The available embolic agents lack X-ray visibility and do not prevent the reflux phenomenon, thus hindering their application for TAE therapy. Herein, we aim to develop a multifunctional embolic agent that combines the X-ray radiopacity with local procoagulant activity. The barium sulfate nanoparticles (BaSO4 NPs) were synthesized and loaded into the polyvinyl alcohol/chitosan (PVA/CS) to prepare the radiopaque BaSO4/PVA/CS microspheres (MS). Thereafter, thrombin was immobilized onto the BaSO4/PVA/CS MS to obtain the thrombin@BaSO4/PVA/CS MS. The prepared BaSO4/PVA/CS MS were highly spherical with diameters ranging from 100 to 300 μm. In vitro CT imaging showed increased X-ray visibility of BaSO4/PVA/CS MS with the increased content of BaSO4 NPs in the PVA/CS MS. The biocompatibility assessments demonstrated that the MS were non-cytotoxic and possessed permissible hemolysis rate. The biofunctionalized thrombin@BaSO4/PVA/CS MS showed improved hemostatic capacity and facilitated hemostasis in vitro. Additionally, in vivo study performed on a rabbit ear embolization model confirmed the excellent X-ray radiopaque stability of the BaSO4/PVA/CS MS. Moreover, both the BaSO4/PVA/CS and thrombin@BaSO4/PVA/CS MS achieved superior embolization effects with progressive ischemic necrosis on the ear tissue and induced prominent ultrastructural changes in the endothelial cells. The findings of this study suggest that the developed MS could act as a radiopaque and hemostatic embolic agent to improve the embolization efficiency., Graphical abstract Image 1, Highlights • Excellent in vitro and in vivo visibility of BaSO4/PVA/CS MS. • Excellent cytocompatibility and hemocompatibility of BaSO4/PVA/CS MS. • Enhanced hemostatic capacity and hemostasis of thrombin@BaSO4/PVA/CS MS. • Potential application of thrombin@BaSO4/PVA/CS MS for in vivo embolization.

Poly(α-l-lysine) (PLL) is a class of water-soluble, cationic biopolymer composed of α-l-lysine structural units. The previous decade witnessed tremendous progress in the synthesis and biomedical applications of PLL and its composites. PLL-based polymers and copolymers, till date, have been extensively explored in the contexts such as antibacterial agents, gene/drug/protein delivery systems, bio-sensing, bio-imaging, and tissue engineering. This review aims to summarize the recent advances in PLL-based nanomaterials in these biomedical fields over the last decade. The review first describes the synthesis of PLL and its derivatives, followed by the main text of their recent biomedical applications and translational studies. Finally, the challenges and perspectives of PLL-based nanomaterials in biomedical fields are addressed., Graphical abstract Image 1, Highlights • Focusing on biomedical applications of PLL-based nanomaterials. • Discussing antibacterial agents, delivery systems, bio-sensing, bio-imaging, and tissue engineering in detail. • Addressing perspectives of PLL-based nanomaterials in biomedical fields.

As an important phenomenon to monitor disease development, cell signaling usually takes place at the interface between organisms/cells or between organisms/cells and abiotic materials. Therefore, finding a strategy to build the specific biomedical interfaces will help regulate information transmission and produce better therapeutic results to benefit patients. In the past decades, plasmas containing energetic and active species have been employed to construct various interfaces to meet biomedical demands such as bacteria inactivation, tissue regeneration, cancer therapy, and so on. Based on the potent functions of plasma modified surfaces, this mini-review is aimed to summarize the state-of-art plasma-activated interfaces and provide guidance to researchers to select the proper plasma and processing conditions to design and prepare interfaces with the optimal biological and related functions. After a brief introduction, plasma-activated interfaces are described and categorized according to different criteria including direct plasma-cells interfaces and indirect plasma-material-cells interfaces and recent research activities on the application of plasma-activated interfaces are described. The authors hope that this mini-review will spur interdisciplinary research efforts in this important area and expedite associated clinical applications., Graphical abstract Image 1, Highlights • The Interfaces between organisms/cells and abiotic materials are crucial for cell signaling. • Plasmas containing energetic and active species are potent tool to construct biomedical interfaces. • The objective here is to summarize recent plasma-activated interfaces to spur interdisciplinary efforts for clinical applications.

Tissue engineering provides a promising avenue for treating cartilage defects. However, great challenges remain in the development of structurally and functionally optimized scaffolds for cartilage repair and regeneration. In this study, decellularized cartilage extracellular matrix (ECM) and waterborne polyurethane (WPU) were employed to construct WPU and WPU-ECM scaffolds by water-based 3D printing using low-temperature deposition manufacturing (LDM) system, which combines rapid deposition manufacturing with phase separation techniques. The scaffolds successfully achieved hierarchical macro‐microporous structures. After adding ECM, WPU scaffolds were markedly optimized in terms of porosity, hydrophilia and bioactive components. Moreover, the optimized WPU-ECM scaffolds were found to be more suitable for cell distribution, adhesion, and proliferation than the WPU scaffolds. Most importantly, the WPU-ECM scaffold could facilitate the production of glycosaminoglycan (GAG) and collagen and the upregulation of cartilage-specific genes. These results indicated that the WPU-ECM scaffold with hierarchical macro‐microporous structures could recreate a favorable microenvironment for cell adhesion, proliferation, differentiation, and ECM production. In vivo studies further revealed that the hierarchical macro‐microporous WPU-ECM scaffold combined with the microfracture procedure successfully regenerated hyaline cartilage in a rabbit model. Six months after implantation, the repaired cartilage showed a similar histological structure and mechanical performance to that of normal cartilage. In conclusion, the hierarchical macro‐microporous WPU-ECM scaffold may be a promising candidate for cartilage tissue engineering applications in the future.

Skin wounds can lead to numerous complications with dangerous health consequences. In this work, magnetite nanoparticles were doped with different concentrations of antimicrobial silver (Ag) ions and incorporated into the electrospun nanofibrous ε-polycaprolactone (PCL) scaffolds. Nanoparticles and scaffolds with various Ag contents were characterized using a range of physicochemical techniques. Ag entered magnetite as cations and preferentially positioned at tetrahedral sites, introducing lattice distortions and topographic irregularities. Amorphization of the structure due to accommodation of Ag expanded the lattice in the bulk and contracted it on the surface, where broadened distribution of Fe–O coordinations was detected. Promoting spin canting and diminishing the double exchange interaction through altered distribution of ferric and ferrous ions, Ag softened the magnetism of magnetite. By making the nanoparticle structure more defective, Ag modified the interface with the polymer and promoted the protrusion of the nanoparticles from the surface of the polymeric nanofibers, thus increasing their roughness and hydrophilicity, with positive repercussions on cell adhesion and growth. Both the viability of human melanocytes and the antibacterial activity against E. coli and S. aureus increased with the concentration of Ag in the magnetite phase of the scaffolds. Skin wound healing rate in rats also increased in direct proportion with the concentration of Ag in the magnetite phase, and no abnormalities in the dermal and epidermal tissues were visible on day 10 in the treatment group. These results imply an excellent potential of these composite nanofibrous scaffolds for use as wound dressings and in other reconstructive skin therapies., Graphical abstract Image 1, Highlights • Electrospun nanofibrous polymeric wound dressings interspersed with magnetite nanoparticles doped with Ag ions were fabricated. • Detailed physicochemical characterization is provided with aid of diffractometric, spectroscopic and microscopic techniques. • Both the viability of melanocytes and the antibacterial activity increased with the addition of Ag ions. • Skin wound healing rate in rats increased to 51 and 92 % on day 10 for dressings without and with Ag, respectively, relative to control. • Animals treated with Ag-doped dressings displayed no atrophy of sebaceous glands and necrosis of hair follicles of control animals.

Here, evodiamine (EVO) and the photosensitizer indocyanine green (ICG) were integrated into a liposomal nanoplatform for noninvasive diagnostic imaging and combinatorial therapy against oral squamous cell carcinoma (OSCC). EVO, as an active component extracted from traditional Chinese medicine, not only functioned as an antitumor chemotherapeutic agent but was also capable of 68Ga-chelation, thus working as a contrast agent for positron emission tomography/computed tomography (PET/CT) imaging. Moreover, EVO could exhibit peroxidase-like catalytic activity, converting endogenous tumor H2O2 into cytotoxic reactive oxygen species (ROS), enabling Chemo catalytic therapy beyond the well-known chemotherapy effect of EVO. As proven by in vitro and in vivo experiments, guided by optical imaging and PET/CT imaging, we show that the theragnostic liposomes have a significant inhibiting effect on in situ tongue tumor through photodynamic therapy combined with chemodynamic chemotherapy., Graphical abstract Image 1, Highlights • Proposing water-soluble nanoliposomes to solve the problem of drug insoluble in water. • Evodiamine is found to have HRP mimic catalase activity. • EI@lipo displays photodynamic/chemodynamic/chemo therapy abilities. • Ei@Lipo significantly inhibits tongue tumor through in situ.

Mesoporous bioactive glasses (MBGs) are promising materials for regenerative medicine, due to their favorable properties including bioactivity and degradability. These key properties, but also their surface area, pore structure and pore volume are strongly dependent on synthesis parameters and glass stoichiometry. However, to date no systematic study on MBG properties covering a broad range of possible compositions exists. Here, 24 MBG compositions in the SiO2–CaO–P2O5 system were synthesized by varying SiO2 (60–90 mol %), CaO and P2O5 content (both 0 to 40 mol-%), while other synthesis parameters were kept constant. Mesopore characteristics, degradability and bioactivity were analysed. The results showed that, within the tested range of compositions, mesopore formation required a molar SiO2 content above 60% but was independent of CaO and P2O5 content. While mesopore size did not depend on glass stoichiometry, mesopore arrangement was influenced by the SiO2 content. Specific surface area and pore volume were slightly altered by the SiO2 content. All materials were degradable; however, degradation as well as bioactivity, i.e. the ability to form a CaP mineral on the surface, depended on stoichiometry. Major differences were found in early surface reactions in simulated body fluid: where some MBGs induced direct hydroxyapatite crystallization, high release of calcium in others resulted in calcite formation. In summary, degradation and bioactivity, both key parameters of MBGs, can be controlled by glass stoichiometry over a broad range while leaving the unique structural parameters of MBGs relatively unaffected. This allows targeted selection of material compositions for specific regenerative medicine applications., Graphical abstract Image 1, Highlights • Mesoporous bioactive glasses can be obtained over a broad range of compositions. • In the SiO2/CaO/P2O5 system up to 15 mol-% P2O5 allow ordered porosity. • In SiO2/P2O5 glasses, up to 30 mol-% P2O5 are possible. • Bioactivity and degradation can be tailored by controlling stoichiometry.

Macrophage-mediated inflammation compromises bone repair in diabetic patients. Electrical signaling cues are known to regulate macrophage functions. However, the biological effects of electrical microenvironment from charged biomaterials on the immune response for regulating osteogenesis under diabetic conditions remain to be elucidated. Herein the endogeneous electrical microenvironment of native bone tissue was recapitulated by fabricating a ferroelectric BaTiO3/poly (vinylidene fluoridetrifluoroethylene) (BTO/P(VDF-TrFE)) nanocomposite membrane. In vitro, the polarized BaTiO3/poly (vinylidene fluoridetrifluoroethylene) (BTO/P(VDF-TrFE)) nanocomposite membranes inhibited high glucose-induced M1-type inflammation, by effecting changes in cell morphology, M1 marker expression and pro-inflammatory cytokine secretion in macrophages. This led to enhanced osteogenic differentiation of human bone marrow mesenchymal stem cells (BM-MSCs). In vivo, the biomimetic electrical microenvironment recapitulated by the polarized nanocomposite membranes switched macrophage phenotype from the pro-inflammatory (M1) into the pro-healing (M2) phenotype, which in turn enhanced bone regeneration in rats with type 2 diabetes mellitus. Mechanistic studies revealed that the biomimetic electrical microenvironment attenuated pro-inflammatory M1 macrophage polarization under hyperglycemic conditions by suppressing expression of AKT2 and IRF5 within the PI3K-AKT signaling pathway, thereby inducing favorable osteo-immunomodulatory effects. Our study thus provides fundamental insights into the biological effects of restoring the electrical microenvironment conducive for osteogenesis under DM conditions, and offers an effective strategy to design functionalized biomaterials for bone regeneration therapy in diabetic patients., Graphical abstract Within the restored electrical microenvironment mediated by polarized ferroelectric nanocomposite membrane, macrophages exhibit suppressed M1 polarization and enhanced M2 polarization. The restored electrical microenvironment downregulates AKT2-IRF5 signaling that induces macrophages to the M2 phenotype, which indicates a favorable osteo-immunomodulatory effects. Hence mimicking the endogeneous electrical microenvironment promotes osteogenic differentiation of BM-MSCs mediated by macrophages, thereby improving bone regeneration.Image 1, Highlights • Electrical microenvironment recapitulated by BTO membranes switched pro-inflammatory M1 into pro-healing M2 phenotype. • The macrophage phenotype transformation from M1 to M2 promotes bone regeneration in rats with type 2 diabetes mellitus. • Restored electrical microenvironment attenuated M1 macrophage polarization via downregulation of AKT2-IRF5.

The deep burn skin injures usually severely damage the dermis with the loss of hair follicle loss, which are difficult to regenerate. Furthermore, severe burns often accompanied with large amount of wound exudates making the wound moist, easily infected, and difficult to heal. Therefore, it is of great clinical significance to develop wound dressings to remove wound exudates and promote hair follicle regeneration. In this study, a sandwich-structured wound dressing (SWD) with Janus membrane property was fabricated by hot compression molding using hydrophilic zinc silicate bioceramics (Hardystonite, ZnCS) and hydrophobic polylactic acid (PLA). This unique organic/inorganic Janus membrane structure revealed excellent exudate absorption property and effectively created a dry wound environment. Meanwhile, the incorporation of ZnCS bioceramic particles endowed the dressing with the bioactivity to promote hair follicle regeneration and wound healing through the release of Zn2+ and SiO32− ions, and this bioactivity of the wound dressing is mainly attributed to the synergistic effect of Zn2+ and SiO32− to promote the recruitment, viability, and differentiation of hair follicle cells. Our study demonstrates that the utilization of the Janus membrane and synergistic effect of different type bioactive ions are effective approaches for the design of wound dressings for burn wound healing., Graphical abstract Image 1, Highlights • A sandwich-structured wound dressing is constructed using ZnCS ceramic powder and PLA fiber membrane (ZnCS-SWD). • ZnCS-SWD has Janus membrane property to absorb wound exudate unidirectionally from wound bed to the dressing. • The combination of Zn2+ and SiO32- ions is found to have a synergistic effect to promote burn wound healing.

A close relationship has been reported to exist between cadherin-mediated cell–cell adhesion and integrin-mediated cell mobility, and protein tyrosine phosphatase 1B (PTP1B) may be involved in maintaining this homeostasis. The stable residence of mesenchymal stem cells (MSCs) and endothelial cells (ECs) in their niches is closely related to the regulation of PTP1B. However, the exact role of the departure of MSCs and ECs from their niches during bone regeneration is largely unknown. Here, we show that the phosphorylation state of PTP1B tyrosine-152 (Y152) plays a central role in initiating the departure of these cells from their niches and their subsequent recruitment to bone defects. Based on our previous design of a PTP1B Y152 region-mimicking peptide (152RM) that significantly inhibits the phosphorylation of PTP1B Y152, further investigations revealed that 152RM enhanced cell migration partly via integrin αvβ3 and promoted MSCs osteogenic differentiation partly by inhibiting ATF3. Moreover, 152RM induced type H vessels formation by activating Notch signaling. Demineralized bone matrix (DBM) scaffolds were fabricated with mesoporous silica nanoparticles (MSNs), and 152RM was then loaded onto them by electrostatic adsorption. The DBM-MSN/152RM scaffolds were demonstrated to induce bone formation and type H vessels expansion in vivo. In conclusion, our data reveal that 152RM contributes to bone formation by coupling osteogenesis with angiogenesis, which may offer a potential therapeutic strategy for bone defects., Graphical abstract Image 1, Highlights • PTP1B plays a dual regulatory role in cadherin- and integrin-related pathways. • Inhibition of PTP1B Y152 phosphorylation enhances the departure of MSCs from the stem cell niche. • DBM-MSN/152RM scaffolds coordinate the recruitment of MSCs and ECs. • DBM-MSN/152RM scaffolds promote bone regeneration and angiogenesis in bone defects.

Stable integration of hydrogel implants with host tissues is of critical importance to cartilage tissue engineering. Designing and fabricating hydrogels with high adhesive strength, stability and regeneration potential are major challenges to be overcome. This study fabricated injectable adhesive hyaluronic acid (HA) hydrogel modified by aldehyde groups and methacrylate (AHAMA) on the polysaccharide backbone with multiple anchoring mechanisms (amide bond through the dynamic Schiff base reaction, hydrogen bond and physical interpenetration). AHAMA hydrogel exhibited significantly improved durability and stability within a humid environment (at least 7 days), together with higher adhesive strength (43 KPa to skin and 52 KPa to glass), as compared to commercial fibrin glue (nearly 10 KPa) and HAMA hydrogel (nearly 20 KPa). The results showed that AHAMA hydrogel was biocompatible and could be easily and rapidly prepared in situ. In vitro cell culture experiments showed that AHAMA hydrogel could enhance proliferation (1.2-folds after 3 days) and migration (1.5-folds after 12 h) of bone marrow stem cells (BMSCs), as compared to cells cultured in a culture dish. Furthermore, in a rat osteochondral defect model, implanted AHAMA hydrogel significantly promoted integration between neo-cartilage and host tissues, and significantly improved cartilage regeneration (modified O'Driscoll histological scores of 16.0 ± 4.1 and 18.3 ± 4.6 after 4 and 12-weeks of post-implantation in AHAMA groups respectively, 12.0 ± 2.7 and 12.2 ± 2.8 respectively in HAMA groups, 9.8 ± 2.4 and 11.5 ± 2.1 respectively in untreated groups). Hence, AHAMA hydrogel is a promising adhesive biomaterial for clinical cartilage regeneration and other biomedical applications., Graphical abstract Image 1, Highlights • Adhesive hydrogel composed of single natural polymer component. • The single component enhance stable and easy to use in surgical operation of hydrogel. • Adhesive hydrogel exhibited strong adhesive strength through multiple anchoring mechanisms. • Adhesive hydrogel promoted integration between neo-cartilage and host tissues, drastically improved cartilage regeneration.

Magnesium metal (Mg) is a promising material for stent applications due to its biocompatibility and ability to be resorbed by the body. Manufacturing of stents by laser cutting has become an industry standard. Our alternative approach uses photo-chemical etching to transfer a pattern of the stent onto a Mg sheet. In this study, we present three stages of creating and validating a stent prototype, which includes design and simulation using finite element analysis (FEA), followed by fabrication based on AZ31 alloy and, finally, in vivo testing in peripheral arteries of domestic pigs. Due to the preliminary character of this study, only six stents were implanted in two domestic farm pigs weighing 25–28 kg and they were evaluated after 28 days, with an interim follow-up on day 14. The left and right superficial femoral, the left iliac, and the right renal artery were selected for this study. The diameters of the stented artery segments were evaluated at the time of implantation, on day 14 and then, finally, on day 28, by quantitative vessel analysis (QVA) using fluoroscopic imaging. Optical Coherence Tomography (OCT) imaging displayed some malposition, breaks, stacking, and protrusion into the lumen at the proximal, distal, and mid-sections of the stented arteries. The stents degraded with time, but simultaneously became embedded in the intima. After 28 days, the animals were euthanized, and explanted vessels were fixed for micro-CT imaging and histology studies. Micro-CT imaging revealed stent morphological and volumetric changes due to the in-body degradation. An in vivo corrosion rate of 0.75 mm/year was obtained by the CT evaluation. The histology suggested no-life threatening effects, although moderate injury, inflammation, and endothelialization scores were observed., Graphical abstract Image 1

In the field of bone defect repair, 3D printed scaffolds have the characteristics of personalized customization and accurate internal structure. However, how to construct a well-structured vascular network quickly and effectively inside the scaffold is essential for bone repair after transplantation. Herein, inspired by the unique biological structure of “lotus seedpod”, hydrogel microspheres encapsulating deferoxamine (DFO) liposomes were prepared through microfluidic technology as “lotus seeds”, and skillfully combined with a three-dimensional (3D) printed bioceramic scaffold with biomimetic “lotus” biological structure which can internally grow blood vessels. In this composite scaffold system, DFO was effectively released by 36% in the first 6 h, which was conducive to promote the growth of blood vessels inside the scaffold quickly. In the following 7 days, the release rate of DFO reached 69%, which was fundamental in the formation of blood vessels inside the scaffold as well as osteogenic differentiation of bone mesenchymal stem cells (BMSCs). It was confirmed that the composite scaffold could significantly promote the human umbilical vein endothelial cells (HUVECs) to form the vascular morphology within 6 h in vitro. In vivo, the composite scaffold increased the expression of vascularization and osteogenic related proteins Hif1-α, CD31, OPN, and OCN in the rat femoral defect model, significantly cutting down the time of bone repair. To sum up, this “lotus seedpod” inspired porous bioceramic 3D printed scaffold with internal vascularization functionality has broad application prospects in the future., Graphical abstract A lotus seedpod-inspired internal vascularized 3D printed bioceramic scaffold with internal vascularization and osteogenesis functionalities was successfully constructed. Bioceramic scaffold takes the role of the lotus “coat” while the DFO-liposome-loaded injectable hydrogel microspheres as “lotus seeds”. The “lotus seeds” are injected directly into the scaffold to construct an internally vascularized bioceramic scaffold to promote the repair bone defects.Image 1, Highlights • 3D printed bioceramic scaffold with biomimetic structure for blood vessels. • Well-structured vascular network quickly and effectively inside the scaffold. • Promoting the growth of blood vessels inside the scaffold quickly. • Increased the expression of vascularization and osteogenic related proteins Hif1-α.

Patients sometimes lose organs and/or organ functions due to disease and injury, which may result in permanent disabilities. Advanced biotechnological practices can now afford victims of these incidences an opportunity to repair some of the damaged tissues or organs without the need for a donor. This can be achieved by reconstruction of the damaged tissue or organ through scaffold and cell technologies. Scaffolds serve as template material for neo-organs to guide and accelerate cell growth. The structure of a scaffold material must meet certain design parameters to achieve optimal functionality in tissue engineering. Pre-requisites include surface compatibility and architectural suitability with the host environment. Polymeric scaffolds derived from polymer blends have the prospects to control the physical and chemical environment of the biological system. In this review, potential roles, general properties, advantages, and disadvantages of poly (lactic acid) and its composites as functional materials for scaffolding will be outlined. PLA and its composites have been subjects of research for some decades due to non-toxicity and the ability to mimic native tissue. Though PLA and composites have demonstrated great potential for various biomedical applications, a lot still needs to be done for them to compete with donor and prosthetic organs.

Lipopolysaccharide (LPS) plays an important role in metabolic syndrome (MetS) and other gut-derived diseases, and detoxifying LPS is considered to be a fundamental approach to prevent and treat these diseases. Here, inspired by the feeding behaviour of scavenger, novel microfluidic microcapsules with alkaline phosphatase (ALP) encapsulation and the scavenger-like molecular sieve shell are presented for cleaning intestinal LPS. Benefiting from the precisely controlled of the pore size and microfluidic electrospray, the generated microcapsules were imparted with porous molecular-sieve shells and ALP encapsulated active cores. These microcapsules could continuously work as an intestinal scavenger after colonized in intestine. It has been demonstrated that the microcapsules could englobe LPS while inhibit the permeation of digestive enzyme, and this ability contributes to promising ALP's activity, protecting cells at the presence of LPS and reducing inflammation. In addition, this scavenger inspired microcapsule could effectively decrease the LPS in organs, reduce inflammation and regulating fat metabolism in vivo. These features make the ALP encapsulated microcapsules an ideal candidate for treating MetS and other LPS related diseases., Graphical abstract The proposed intestinal scavenger microcapsules fabricated by microfluidic electrospray were imparted with scavenger-like molecular sieve shell are presented for cleaning intestinal LPS. It has been demonstrated that the microcapsules could englobe LPS while inhibit the permeation of digestive enzyme, and this ability contributes to promising ALP's activity, protecting cells at the presence of LPS and reducing inflammation.Image 1, Highlights • A microfluidic electrospray microcapsule with molecular sieve shell. • Microcapsules protect the alkaline phosphatase from digestive enzyme. • Microcapsules allow the permeation of lipopolysaccharide.

Iodine ion is one of the most indispensable anions in living organisms, particularly being an important substance for the synthesis of thyroid hormones. Curcumin is a yellow-orange polyphenol compound derived from the rhizome of Curcuma longa L., which has been commonly used as a spice and natural coloring agent, food additives, cosmetics as well as Chinese medicine. However, excess curcumin may cause DNA inactivation, lead to a decrease in intracellular ATP levels, and trigger the tissue necrosis. Therefore, quantitative detection of iodine and curcumin is of great significance in the fields of food and life sciences. Herein, we develop nitrogen-doped fluorescent carbon dots (NCDs) as a multi-mechanism detection for iodide and curcumin in actual complex biological and food samples, which was prepared by a one-step solid-phase synthesis using tartaric acid and urea as precursors without adding any other reagents. An assembled NCDs-Hg2+ fluorescence-enhanced sensor for the quantitative detection of I− was established based on a fluorescence “turn-off-on” mechanism in a linear range of 0.3–15 μM with a detection limit of 69.4 nM and successfully quantified trace amounts of I− in water samples and urine sample. Meanwhile, the as-synthesized NCDs also can be used as a fluorescent quenched sensor for curcumin detection based on the synergistic internal filtration effect (IFE) and static quenching, achieving a good linear range of 0.1–20 μM with a satisfactory detection limit of 29.8 nM. These results indicate that carbon dots are potential sensing materials for iodine and curcumin detection for the good of our health., Graphical abstract Image 1, Highlights • Facile synthesis of nitrogen-doped carbon dots with tartaric acid and urea as precursors without any additives. • High-sensitive determination of I− with assembled NCDs-Hg2+ fluorescence-enhanced sensor. • Fluorescence sensor for curcumin detection with good linear response, high specificity, and high sensitivity. • Successful applications for I− and curcumin in water, urine, and foods.

Both phototherapy via photocatalysts and physical puncture by artificial nanostructures are promising substitutes for antibiotics when treating drug-resistant bacterial infectious diseases. However, the photodynamic therapeutic efficacy of photocatalysts is seriously restricted by the rapid recombination of photogenerated electron–hole pairs. Meanwhile, the nanostructures of physical puncture are limited to two-dimensional (2D) platforms, and they cannot be fully used yet. Thus, this research developed a synergistic system of Ag3PO4 nanoparticles (NPs), decorated with black urchin-like defective TiO2 (BU–TiO2-X/Ag3PO4). These NPs had a decreased bandgap compared to BU-TiO2-X, and BU-TiO2-X/Ag3PO4 (3:1) exhibited the lowest bandgap and the highest separation efficiency for photogenerated electron–hole pairs. After combination with BU-TiO2-X, the photostability of Ag3PO4 improved because the oxygen vacancy of BU-TiO2-X retards the reduction of Ag+ in Ag3PO4 into Ag0, thus reducing its toxicity. In addition, the nanospikes on the surface of BU-TiO2-X can, from all directions, physically puncture bacterial cells, thus assisting the hybrid's photodynamic therapeutic effects, alongside the small amount of Ag+ released from Ag3PO4. This achieves synergy, endowing the hybrid with high antibacterial efficacy of 99.76 ± 0.15% and 99.85 ± 0.09% against Escherichia coli and Staphylococcus aureus, respectively, after light irradiation for 20 min followed by darkness for 12 h. It is anticipated that these findings may bring new insight for developing synergistic treatment strategies against bacterial infectious diseases or pathogenic bacterial polluted environments., Graphical abstract Image 1, Highlights • BU-TiO2-X/Ag3PO4 (3:1) hybrid improved the photostability of Ag3PO4. • BU-TiO2-X/Ag3PO4 (3:1) hybrid exhibited outstanding photodynamic therapeutic effects. • The nanospikes from all directions on the BU-TiO2-X physically punctured bacterial cells. • The physical puncture combined with the Ag+ released by Ag3PO4 had long-term bacteriostatic efficacy.

Brain barrier is both a protective permeability hurdle and a limitation site where therapeutic agents are excluded to enter the target region. Designing drug vehicle to overcome this notorious barrier bottle is challenging. Herein, we construct a stimuli-responsive self-assembled nanovesicle that delivers water-soluble drugs to prevent the efflux transport of brain barriers by responding to the endogenously occurring signals in Alzheimer's disease (AD) brain microenvironment. Once stimuli-responsive vesicles are accumulated in intracerebrally, the intrinsically occurring legumain endopeptidase cleaves the Ac-Ala-Ala-Asn-Cys-Asp (AK) short peptide on the drug vesicles to expose the 1,2 thiol amino group to cyclize with the cyano groups on 2-cyano-6-aminobenzothiazole (CABT) of the chaperone vesicles, thus triggering the formation of cross-linked micrometre-scale vesicles. Such a structural alteration completely prevents further brain barriers efflux. The superior neuroprotective capacity of cross-linked vesicles is validated in senescence accelerated mouse prone 8 (SAMP8). This smart multi-drug delivery vesicle is promising to serve as a powerful system for AD treatment and can be adapted for the therapy of other central nervous system (CNS) disorders., Graphical abstract a) Responsive cross-linked of large compound vesicles formed in intracerebrally. b) Inhibition of brain barrier efflux and synergistic treatment of AD.Image 1, Highlights • Drug efflux is a bottleneck for treating many disorders, such as Alzheimer's diseases (AD). • The key to success in drug brain parenchyma anchoring is specific targeting delivery. • Functionalized vesicles provided the possibility of inhibiting the efflux transport and increasing drug brain enrichment. • Legumain-induced aggregated multi-drug delivery vesicle is promising to serve as a powerful system for AD treatment.

Severe plastic deformation (SPD) with deformation strain significantly larger than one is effective to strengthen metals and alloys. However, such a method will not work for Mg alloys due to their low deformability. In view of this problem, we propose a new alloy strengthening scheme of low-strain deformation, which is to introduce massive twins and stacking faults in coarse grain interior by rotary swaging (RS) at room temperature. By using this scheme, we successfully prepared an ultra-light bulk Mg-Li alloy with new strength record. This paper explored a new strengthening way of low deformation strain for metals and alloys and successfully prepared a strongest ultra-light Mg–Li alloy by low-strain rotary swaging process.

Cell-mediated drug delivery system (CDDS) has shown great potential for cancer therapy. However, a single cell-mediated drug delivery mechanism has not generally been successful, particularly for systemic administration. To augment the antitumor therapy efficacy, herein, we propose a strategy of cell relay-delivery for the use of artificially damaging/aging erythrocytes to hitchhike on circulating monocytes/macrophages for intratumoral accumulation of anticancer drugs. This biomimetic relay-delivery strategy was derived from the manner in which circulating monocytes/macrophages in body specifically engulf damaged/senescent erythrocytes and actively transmigrate into the tumor bulk. The strategy elegantly combines the natural functions of both cells, which therefore provides a new perspective to challenge current obstacles in drug delivery. According to the strategy, we developed biotinylated erythrocyte-poly (lactic-co-glycolic acid) (PLGA) nanoparticle hybrid DDSs (bE-NPs) using avidin-biotin coupling. In such a system, biotinylated erythrocytes can mimic the natural property of damaged/senescent erythrocytes, while PLGA NPs are capable of encapsulating anticancer drugs and promoting sustained drug release. Anticancer drugs can effectively target tumor sites by two steps. First, by using biotinylated erythrocytes as the carrier, the drug-loaded PLGA NPs could be specifically phagocytized by monocytes/macrophages. Second, by taking advantage of the tumor-tropic property of monocytes/macrophages, the drug-loaded PLGA NPs could be efficiently transported into the tumor bulk. After encapsulating vincristine (VIN) as the model drug, bE-NPs exhibited the most favorable antitumor effects in vitro and in vivo by the cell relay-delivery effect. These results demonstrate that the cell relay-delivery provides a potential method for improving tumor treatment efficacy., Graphical abstract Image 1, Highlights • The strategy of cell relay-delivery combines the functions of monocytes/macrophages and damaged/senescent erythrocytes. • According to the strategy of cell relay-delivery, the bE-NPs can effectively target tumor sites by two steps. • The bE-NPs demonstrated the synergistic power of different size-scale technologies.

Application of extracorporeal circuits and indwelling medical devices has saved many lives. However, it is accompanied with two major complications: thrombosis and infection. To address this issue, we apply therapeutic nitric oxide gas (NO) and antibacterial peptide for synergistically tailoring such devices for surface anti-thrombogenic and antifouling dual functions. Such functional surface is realized by stepwise conjugation of NO-generating compound of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelated copper ions (Cu-DOTA) and dibenzylcyclooctyne- (DBCO-) modified antimicrobial peptide based on carbodiimide and click chemistry respectively. The integration of peptide and Cu-DOTA grants the modified surface the ability to not only efficiently inhibit bacterial growth, but also catalytically generate NO from endogenous s-nitrosothiols (RSNO) to reduce adhesion and activation of platelets, preventing the formation of thrombus. We envision that the stepwise synergistic modification strategy by using anticoagulant NO and antibacterial peptide would facilitate the surface multifunctional engineering of extracorporeal circuits and indwelling medical devices, with reduced clinical complications associated with thrombosis and infection., Graphical abstract Image 1, Highlights • We report a bionic surface strategy for blood-contacting devices by integrating anti-thrombogenic and anti-microbial dual functions. Here, we engineer an endothelium-mimicking surface by combination of the nitric oxide (NO)-generating property and anti-microbial functions of a healthy endothelium, in which the generated gas signal molecule NO and the anti-microbial peptide (AMP) jointly provide synergistic effects against thrombogenicity and biofouling. • An endothelium-bionic surface strategy is proposed for tailoring surface multi-functionalities. • Carbodiimide and click chemistries were used for realizing synergistic tethering of NO-generating species and bio-clickable antimicrobial peptide. • The integration of NO and antimicrobial peptide imparts the tubing surface with anti-thrombogenic and anti-fouling dual functions. The integration of NO releasing and AMP tethering endows the tubing surface with significant anti-thrombogenic and anti-fouling properties. We envision that this bio-inspired surface engineering strategy will provide a promising solution to address the clinical issues.

The Pickering emulsion polymerization of styrene (St), divinylbenzene (DVB) as a crosslinking agent, and sodium 4-vinyl benzene sulfonate (VBS) used for in situ surface-modification of silica nanoparticles (SNps) was investigated. At 1.0 wt% DVB, amphiphilic SNps with hydrophobic patches were formed, further self-assembling into copolymer-SNps clusters occurred. Subsequently, these clusters grow by monomer swelling to finally lead to the formation of core-shell polymer microspheres. Unlike the hydrophilic patchy SNps, at 2.0 and 3.0 wt% DVB, surface-patterned SNps with higher effective hydrophobicity do not self-assemble in the water phase but rather lead to the formation of monoliths. The polymerization mechanisms related to the formation of polymer silica-coated microspheres hybrid-materials, or percolated monoliths with bi-continuous porosity, formed by interfacially jammed emulsion gel (bijels) templates, are discussed herein.

Periodontitis is a common disease that causes periodontium defects and tooth loss. Controlling inflammation and tissue regeneration are two key strategies in the treatment of periodontitis. Tetrahedral framework nucleic acids can modulate multiple biological behaviors, and thus, their biological applications have been widely explored. In this study, we investigated the effect of tFNAs on periodontium under inflammatory conditions. Lipopolysaccharide and silk ligature were used to induce inflammation in vivo and in vitro. The results displayed that tFNAs decreased the release of pro-inflammatory cytokines and levels of cellular reactive oxygen species in periodontal ligament stem cells, which promoted osteogenic differentiation. Furthermore, animal experiments showed that tFNAs ameliorated the inflammation of the periodontium and protect periodontal tissue, especially reducing alveolar bone absorption by decreasing inflammatory infiltration and inhibiting osteoclast formation. These findings suggest that tFNAs can significantly improve the therapeutic effect of periodontitis and have the great potential significance in the field of periodontal tissue regeneration., Graphical abstract Image 1, Highlights • tFNAs decreased the release of pro-inflammatory cytokines and promoted osteogenic differentiation. • tFNAs ameliorated the inflammation of the periodontium and protect periodontal tissue. • tFNAs can significantly improve the therapeutic effect of periodontitis.

Entanglement dynamics of uniaxially-oriented, disentangled ultra-high molecular weight polyethylene nanocomposites modified with gold nanoparticles are investigated, using dielectric spectroscopy, during the transition to melt state. The dc conduction is approximately calculated via the logarithmic derivative of dielectric permittivity and is observed to decrease with the formation of entanglements. As the draw ratio increases, the progressive formation of entanglements resulted in a stronger dc conductivity decrease due to the loss of orientation in the pre-melt crystalline and partially oriented amorphous chain segments. Additionally, a sharp peak is obtained in the absence of dc conductivity, attributed to the dipolar contribution of the Maxwell-Wagner-Sillars (MWS) interfacial polarization between the gold nanoparticles and the polymer chains. The relaxation time of the MWS interfacial polarization increases with the progressive formation of entanglements, as observed in a previous study. The results presented shed light on the process of entanglement formation in oriented ultrahigh molecular weight polyethylene nanocomposites.

The study presents new on/off switchable nanofiber membranes with high sensitivity for detecting Co2+ and Cu2+ ions. The nanofiber membranes were fabricated by electrospinning (ES) the poly[(2-hydroxyethylmethacrylate-co-N-methylolacrylamide)] [poly(HEMA-co-NMA)] copolymer with different quantities of 2,2′-bipyridine-3,3′-diol (BPDO). Poly(HEMA-co-NMA)random copolymers with various molar ratios of the HEMA and NMA monomers were synthesized by free radical polymerization. The HEMA and NMA moieties were specifically selected to promote hydrophilicity and crosslinking reactions, which ultimately support a mechanically stable structure in aqueous media. ES nanofiber membranes S1-0.5, with a HEMA:NMA molar ratio of 77:23 and 0.5 wt% of BPDO showed strong photoluminescence quenching upon exposure to Co2+ and Cu2+ ions at concentrations ranging from 10–7 to 10–4 M. Moreover, the nanofiber membranes exhibited reversibile on/off fluorescence emission properties upon the sequential addition of Cu2+ ions and ethylenediaminetetraacetic acid (EDTA). These results demonstrate a simple fabrication strategy for nanofiber membranes that have the potential to be effective for the real-time sensing of metal ions.

Vascular diseases are the most prevalent cause of ischemic necrosis of tissue and organ, which even result in dysfunction and death. Vascular regeneration or artificial vascular graft, as the conventional treatment modality, has received keen attentions. However, small-diameter (diameter, Graphical abstract Image 1, Highlights • This paper reviews challenges and strategies for enhanced in situ vascularization. • Strategies for homing, adhesion and activation of EPCs and ECs are summarized. • Approaches to prevent thrombogenesis and IH for long-term lumen patency are introduced. • Immune system plays a role in modulating biological behaviors of ECs and SMCs. • Perspectives for future development of vascular grafts are proposed.

A nano/ultrafine grained immiscible Fe-Cu alloy was produced using selective laser melting (SLM) with an average grain size of 250 nm and many 50–100 nm, the finest ever achieved using additive manufacturing (AM). The substantial grain refinement was attributed to liquid separation, monotectic reaction and solid-state phase transformations upon cyclic heating. Cu particles of ∼5 nm in size and ∼10 nm in spacing were contained in some grains, resulting in dispersion strengthening which, together with grain boundary strengthening, led to a significant increase in the yield strength from ∼400 MPa in an SLM-fabricated Fe to ∼900 MPa in Fe-Cu.

The development of carbon fabric reinforced epoxy (CF/EP) composites with excellent mechanical properties and high flame retardancy is desired in both scientific and industrial communities. In this work, the phosphorus-containing flame retardant 9,10-dihydro-9-oxa-10-phosphaphenanthrene 10-oxide (DOPO) based amine functional silane coupling agent was coated on carbon fabric, aiming to promote the interfacial charring behavior, and at the same time, improve the fiber-matrix interfacial strength. With only a small proportion of the hybrid Si/N/P coating on the fiber surface, the resultant composite laminate showed a 26 and 31% reduction in peak heat release rate and smoke production rate, respectively. Under the combustion, the surface grafted phosphorus compounds effectively promoted the interfacial charring behavior of EP composites. An integrated and dense char layer composed of carbon fabric with sealed gaps was formed to protect the underlying polymer materials in the condensed phase. In addition, the fiber push-in test clearly revealed an increased fibermatrix interfacial strength (35%) due to the existence of amine groups on the fiber surface. The provided Si/N/P hybrid surface functionalization strategy proved to be an effective approach to prepare high-performance flame retardant CF/EP composite.

Micro/nanomotors (MNMs) are miniaturized machines that can convert many kinds of energy into mechanical motion. Over the past decades, a variety of driving mechanisms have been developed, which have greatly extended the application scenarios of MNMs. Enzymes exist in natural organisms which can convert chemical energy into mechanical force. It is an innovative attempt to utilize enzymes as biocatalyst providing driving force for MNMs. The fuels for enzymatic reactions are biofriendly as compared to traditional counterparts, which makes enzyme-powered micro/nanomotors (EMNMs) of great value in biomedical field for their nature of biocompatibility. Until now, EMNMs with various shapes can be propelled by catalase, urease and many others. Also, they can be endowed with multiple functionalities to accomplish on-demand tasks. Herein, combined with the development process of EMNMs, we are committed to present a comprehensive understanding of EMNMs, including their types, propelling principles, and potential applications. In this review, we will introduce single enzyme that can be used as motor, enzyme powered molecule motors and other micro/nano-architectures. The fundamental mechanism of energy conversion process of EMNMs and crucial factors that affect their movement behavior will be discussed. The current progress of proof-of-concept applications of EMNMs will also be elaborated in detail. At last, we will summarize and prospect the opportunities and challenges that EMNMs will face in their future development., Graphical abstract Image 1, Highlights • Clear classification and description of different enzyme-powered micro/nanomotors (EMNMs). • Discussion of the fundamental mechanism of energy conversion process of EMNMs and their movement influence factors. • Introduction of the current progress of proof-of-concept applications of EMNMs.

Appropriate biomimetic scaffolds created via 3D bioprinting are promising methods for treating damaged menisci. However, given the unique anatomical structure and complex stress environment of the meniscus, many studies have adopted various techniques to take full advantage of different materials, such as the printing combined with infusion, or electrospining, to chase the biomimetic meniscus, which makes the process complicated to some extent. Some researchers have tried to tackle the challenges only by 3D biopringting, while its alternative materials and models have been constrained. In this study, based on a multilayer biomimetic strategy, we optimized the preparation of meniscus-derived bioink, gelatin methacrylate (GelMA)/meniscal extracellular matrix (MECM), to take printability and cytocompatibility into account together. Subsequently, a customized 3D bioprinting system featuring a dual nozzle + multitemperature printing was used to integrate the advantages of polycaprolactone (PCL) and meniscal fibrocartilage chondrocytes (MFCs)-laden GelMA/MECM bioink to complete the biomimetic meniscal scaffold, which had the best biomimetic features in terms of morphology and components. Furthermore, cell viability, mechanics, biodegradation and tissue formation in vivo were performed to ensure that the scaffold had sufficient feasibility and functionality, thereby providing a reliable basis for its application in tissue engineering., Graphical abstract Image 1, Highlights • We have optimized the preparation of meniscus-derived bioink with good printability and cytocompatibility. • A customized printing system for biomimetic meniscus, the dual-nozzle + multitemperature printing system was developed. • We have achieved multilayer meniscal biomimetic strategy, especially the best biomimetics of morphology and components. • Focusing on application prospect, we designed a few experiments to verity the feasibility and functionality of the scaffold.

Combining chemo-therapeutics with immune checkpoint inhibitors facilitates killing cancer cells and activating the immune system through inhibiting immune escape. However, their treatment effects remain limited due to the compromised accumulation of both drugs and inhibitors in certain tumor tissues. Herein, a new poly (acrylamide-co-acrylonitrile-co-vinylimidazole-co-bis(2-methacryloyl) oxyethyl disulfide) (PAAVB) polymer-based intelligent platform with controllable upper critical solution temperature (UCST) was used for the simultaneous delivery of paclitaxel (PTX) and curcumin (CUR). Additionally, a hyaluronic acid (HA) layer was coated on the surface of PAAVB NPs to target the CD44-overexpressed tumor cells. The proposed nanomedicine demonstrated a gratifying accumulation in tumor tissue and uptake by cancer cells. Then, the acidic microenvironment and high level of glutathione (GSH) in cancer cells could spontaneously decrease the UCST of polymer, leading to the disassembly of the NPs and rapid drug release at body temperature without extra-stimuli. Significantly, the released PTX and CUR could induce the immunogenic cell death (ICD) to promote adaptive anti-tumor immunogenicity and inhibit immunosuppression through suppressing the activity of indoleamine 2,3-dioxygenase 1 (IDO1) enzyme respectively. Therefore, the synergism of this intelligent nanomedicine can suppress primary breast tumor growth and inhibit their lung metastasis., Graphical abstract An intelligent nano-platform with controllable upper critical solution temperature (UCST) for simultaneous targeted delivery of paclitaxel and curcumin to achieve immunogenic cell death and reverse immunosuppression.Image 1, Highlights • A new copolymer PAAVB was prepared with pH- and GSH- controllable upper critical solution temperature (UCST) properties. • A nano-platform with PAAVB copolymer core and HA shell was developed and showed the capability to deliver PTX and CUR. • The antitumor immune response was synergistically stimulated by PTX-induced ICD and CUR induced IDO1activity suppression. • The synergism of intelligent nanomedicine could suppress the primary breast tumor growth and inhibit their lung metastasis.

Currently the standard surgical treatment for bladder defects is augmentation cystoplasty with autologous tissues, which has many side effects. Biomaterials such as small intestine submucosa (SIS) can provide an alternative scaffold for the repair as bladder patches. Previous studies have shown that SIS could enhance the capacity and compliance of the bladder, but its application is hindered by issues like limited smooth muscle regeneration and stone formation since the fast degradation and poor mechanical properties of the SIS. Procyanidins (PC), a natural bio-crosslinking agent, has shown anti-calcification, anti-inflammatory and anti-oxidation properties. More importantly, PC and SIS can crosslink through hydrogen bonds, which may endow the material with enhanced mechanical property and stabilized functionalities. In this study, various concentrations of PC-crosslinked SIS (PC-SIS) were prepared to repair the full-thickness bladder defects, with an aim to reduce complications and enhance bladder functions. In vitro assays showed that the crosslinking has conferred the biomaterial with superior mechanical property and anti-calcification property, ability to promote smooth muscle cell adhesion and upregulate functional genes expression. Using a rabbit model with bladder defects, we demonstrated that the PC-SIS scaffold can rapidly promote in situ tissue regrowth and regeneration, in particular smooth muscle remodeling and improvement of urinary functions. The PC-SIS scaffold has therefore provided a promising material for the reconstruction of a functional bladder., Graphical abstract Schematic illustration of the PC-SIS membrane for bladder augmentation.Image 1, Highlights • PC-SIS showed good biocompatibility, improved mechanical properties and anti-calcification ability in vitro. • PC-SIS promoted tissue regeneration especially smooth muscle remodeling in a rabbit full-thickness bladder defect model. • PC-SIS enhanced bladder compliance, and would not lead to progressive renal disease in the in vivo model.

Low patency ratio of small-diameter vascular grafts remains a major challenge due to the occurrence of thrombosis formation and intimal hyperplasia after transplantation. Although developing the functional coating with release of bioactive molecules on the surface of small-diameter vascular grafts are reported as an effective strategy to improve their patency ratios, it is still difficult for current functional coatings cooperating with spatiotemporal control of bioactive molecules release to mimic the sequential requirements for antithrombogenicity and endothelialization. Herein, on basis of 3D-printed polyelectrolyte-based vascular grafts, a biologically inspired release system with sequential release in spatiotemporal coordination of dual molecules through an electrostatic self-assembly was first described. A series of tubes with tunable diameters were initially fabricated by a coaxial extrusion printing method with customized nozzles, in which a polyelectrolyte ink containing of ε-polylysine and sodium alginate was used. Further, dual bioactive molecules, heparin with negative charges and Tyr-Ile-Gly-Ser-Arg (YIGSR) peptide with positive charges were layer-by-layer assembled onto the surface of these 3D-printed tubes. Due to the electrostatic interaction, the sequential release of heparin and YIGSR was demonstrated and could construct a dynamic microenvironment that was thus conducive to the antithrombogenicity and endothelialization. This study opens a new avenue to fabricate a small-diameter vascular graft with a biologically inspired release system based on electrostatic interaction, revealing a huge potential for development of small-diameter artificial vascular grafts with good patency., Graphical abstract Image 1, Highlights • A series of polyelectrolyte-based tubes with tunable diameters are fabricated via coaxial extrusion printing. • Heparin and YIGSR were assembled layer-by-layer onto the printed tubes surface via electrostatic interaction. • The sequential release behavior of heparin and YIGSR can benefit for their antithrombogenicity and endothelialization.

High-temperature shape memory alloys (HTSMAs) show enormous potential for applications as energy conversion devices, actuators and sensors in automotive, aerospace, and energy exploration industries, but they suffer from strength decrease and microstructural instability at elevated temperatures, rendering it difficult to achieve satisfactory high-temperature superelasticity. Here, a novel Ti20Hf15Zr15Cu25Ni25 high-entropy HTSMA exhibiting large superelasticity with a fully recoverable strain of 4.0% at temperatures up to 285°C is designed with the high-entropy alloy concept by employing the sluggish diffusion and severe lattice distortion effects to suppress thermal softening. This work illuminates the design of novel high-performance functional materials for high-temperature applications.

Due to the complex interplay between composition, synthesis parameters and the performance of thermoelectric materials, the optimization of thermoelectric materials needs to be complemented by modelling. A relatively simple and thus popular approach is the so called single parabolic band model, which allows for an efficient optimization of the material properties and a benchmarking of different materials based on relatively few, well available experimental results. As complex band structures are common for high performance materials, single parabolic band modelling is also employed with apparent success for material systems where the underlying assumptions are not well fulfilled. In order to assess the validity of a single parabolic band analysis for such systems, the thermoelectric properties for two model systems are calculated: one with a single band that is twofold degenerate and one with a light and a heavy band. Even if the density of states masses and the scattering potentials are kept identical, the transport properties and in particular the Hall coefficients differ significantly, which leads to an incorrectly determined carrier concentration. As the carrier concentration is the base for the single parabolic band analysis, all the quantities obtained from it (optimum carrier concentration, effective mass, deformation potential) are determined incorrectly as well.

Digenite (Cu1.8S) as a potential p-type thermoelectric (TE) material has attracted extensive attention due to its environmental benign, abundant resources and low cost of component elements. In this study, the TE properties of MnxCu1.8S bulk samples prepared by mechanical alloying (MA) combined with spark plasma sintering (SPS) were investigated. Doping Mn would initially substitute Cu and tune the band structure of Cu1.8S with an enlarged band gap Eg. However, if Mn content is beyond the solubility limit of x = 0.01 in Cu1.8S will cause the formation of MnS, which contributes to the formation of Cu-rich phases at 0.02 ≤ x ≤ 0.08. Benefiting from the synergetic scattering effect of point defects ( Mn Cu • , V S • • ) and MnS, Cu1.96S, Cu1.97S, Cu2S phases, the lowest thermal conductivity κ value of 0.75 W m−1K−1 was obtained at 773 K for Mn0.08Cu1.8S. Along with the decreased κ, the highest figure of merit ZT value of 0.92 at 773 K achieved in Mn0.08Cu1.8S bulk sample. A maximum engineering ZTeng of 0.3 and its efficiency ηmax of about 6% were obtained at 323–773 K, which is almost 3 times than that of the pristine Cu1.8S (ηmax = 2.2%). Introducing Mn in Cu1.8S is an effective and convenient strategy to improve TE performance.