Search

We study the collision frequencies of charged particles in the complex plasmas with the non-Maxwellian velocity distributions. The average collision frequencies of electron-ion, electron-electron and ion-ion are derived in the two-parameter (r,s) and the three-parameter (a,r,s) velocity distributions, respectively. We show that these average collision frequencies in the complex plasmas depend strongly on the parameters in the non-Maxwellian distributions and thus are significant deviations from those in the plasmas with a Maxwell velocity distribution. Numerical analyses are made of the effects of the parameters on the average collision frequencies. The results have important effect on transport coefficients and their properties of charged particles in the highly ionized complex plasmas with the non-Maxwell distributions., 14 pages, 5 figures, 49 references. arXiv admin note: text overlap with arXiv:2101.02066 by other authors

Porous polymer scaffolds are essential materials for tissue engineering because they can be easily processed to deliver stem cells or bioactive factors. However, scaffolds made of synthetic polymers normally lack a bioactive cell-material interface and undergo a burst release of growth factors, which may hinder their further application in tissue engineering. In this paper, a metal-phenolic network (MPN) was interfacially constructed on the pore surface of a porous poly(dl-lactide) (PPLA) scaffold. Based on the molecular gating property of the MPN supramolecular structure, the PPLA@MPN scaffold achieved the sustained release of the loaded molecules. In addition, the MPN coating provided a bioactive interface, thus encouraging the migration and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). The PPLA@MPN scaffolds exhibited enhanced bone regeneration in a rat femoral defect model in vivo compared to PPLA, which is ascribed to the combined effect of sustained bone morphogenetic protein-2 (BMP-2) release and the osteogenic ability of MPN. This nanodressing technique provides a viable and straightforward strategy for enhancing the performance of porous polymer scaffolds in bone tissue engineering.

Conventional treatment to periodontal and many other bone defects requires the use of barrier membranes to guided tissue regeneration (GTR) and guided bone regeneration (GBR). However, current barrier membranes normally lack of the ability to actively regulate the bone repairing process. Herein, we proposed a biomimetic bone tissue engineering strategy enabled by a new type of Janus porous polylactic acid membrane (PLAM), which was fabricated by combining unidirectional evaporation-induced pore formation with subsequent self-assembly of a bioactive metal-phenolic network (MPN) nanointerface. The prepared PLAM-MPN simultaneously possesses barrier function on the dense side and bone-forming function on the porous side. In vitro, the presence of MPN nanointerface potently alleviated the proinflammatory polarization of rat bone marrow-derived macrophages (BMDMs), induced angiogenesis of human umbilical vein endothelial cells (HUVECs), and enhanced the attachment, migration and osteogenic differentiation of periodontal ligament stem cells (PDLSCs). The implantation of PLAM-MPN into rat periodontal bone defects remarkably enhanced bone regeneration. This bioactive MPN nanointerface within a Janus porous membrane possesses versatile capacities to regulate cell physiology favoring bone regeneration, demonstrating great potential as GTR and GBR membranes for clinical applications.

Directed differentiation enables the production of a specific cell type by manipulating signals in development. However, there is a lack of effective means to accelerate the regeneration of neurons of particular subtypes for pathogenesis and clinical therapy. In this study, we find that hydroxyapatite (HAp) nanorods promote neural differentiation of neural stem cells due to their chemical compositions. Lysosome-mediated degradation of HAp nanorods elevates intracellular calcium concentrations and accelerates GABAergic neurogenesis. As a mechanism, the enhanced activity of a Ca2+ peak initiated by HAp nanorods leads to the activation of c-Jun and thus suppresses the expression of GABAergic/glutamatergic selection gene TLX3. We demonstrate the capability of HAp nanorods in promoting the differentiation into GABAergic neurons at both molecular and cellular function levels. Given that GABAergic neurons are responsible for various physiological and pathological processes, our findings open up enormous opportunities in efficient and precise stem cell therapy of neurodegenerative diseases.

Existing local drug delivery systems for periodontitis suffer from poor antibacterial effect and unsatisfied periodontal regeneration. In this study, a smart gingipain-responsive hydrogel (PEGPD@SDF-1) was synthesized as an environmentally sensitive carrier for on-demand drug delivery. The PEGPD@SDF-1 hydrogel was synthesized from polyethylene glycol diacrylate (PEG-DA) based scaffolds, dithiothreitol (DTT), and a novel designed functional peptide module (FPM) via Michael-type addition reaction, and the hydrogel was further loaded with stromal cell derived factor-1 (SDF-1). The FPM exhibiting a structure of anchor peptide-short antimicrobial peptide (SAMP)-anchor peptide could be cleaved by gingipain specifically, and the SAMP was released out of the hydrogel for antibacterial effect in response to gingipain. The hydrogel properties were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), swelling ratio analysis, degradation evaluation, and release curve description of the SAMP and SDF-1. Results in vitro indicated the PEGPD@SDF-1 hydrogel exhibited preferable biocompatibility and could promote the proliferation, migration, and osteogenic differentiation of periodontal ligament stem cells (PDLSCs). Antibacterial testing demonstrated that the PEGPD@SDF-1 hydrogel released the SAMP stressfully in response to gingipain stimulation, thereby strongly inhibiting the growth of Porphyromonas gingivalis. Furthermore, the study in vivo indicated that the PEGPD@SDF-1 hydrogel inhibited P. gingivalis reproduction, created a low-inflammatory environment, facilitated the recruitment of CD90+/CD34- stromal cells, and induced osteogenesis. Taken together, these results suggest that the gingipain-responsive PEGPD@SDF-1 hydrogel could facilitate in situ periodontal tissue regeneration and is a promising candidate for the on-demand local drug delivery system for periodontitis.

Osteoimmunomodulation was identified as a new and important strategy to enhance osteogenic differentiation together with other osteogenic approaches. However, approaches regulating osteogenic differentiation and macrophage polarization to remodel an osteoinductive microenvironment are separate and complicated. Therefore, the design and synthesis of one biomaterial that couples the osteogenic performance and immunomodulatory ability is a major challenge for efficient bone repair. In this study, self-assembled iron-catechin nanoparticles (Fe-cat NPs) were designed based on the coordinated reaction between iron ions and catechin and synthesized via a facile one-pot strategy. Interestingly, Fe-cat NPs show intracellular pH-responsive disassembly and release catechin molecules under the low pH of lysosomes after endocytosis. This strategy delivers catechin intracellularly and then enhances the osteogenic differentiation while inhibits the adipogenic differentiation of human adipose-derived stem cells (hADSCs). More importantly, Fe-cat NPs remodel the osteogenic immune microenvironment by resisting inflammation and promoting M2 polarization of macrophages. As a promising metal-organic nanodrug, the intracellular pH-responsive Fe-cat NPs significantly enhance the therapeutic effect of bone regneration by orchestrating osteogenic differentiation and immunomodulation, which may have great potential in bone tissue engineering.

Based on the specific tumor microenvironment, characterized by an overproduction of H2O2 and a high glutathione (GSH) concentration, the cascade reactions of nanomaterials, capable of mediating GSH depletion and reactive oxygen species (ROS) generation, have become a popular strategy to increase cancer therapy efficiency. In this study, we exploited reduced graphene oxide (rGO), one of the most promising graphene-based materials, in combination with manganese dioxide nanoparticles (MnO2 NPs) to design a multifunctional nanoplatform (rGO@MnO2) for efficient photothermal/chemodynamic combined therapies. MnO2 NPs were anchored onto the surface of rGO nanosheets (rGO NSs). MnO2 NPs oxidize intracellular GSH, and the generated Mn2+ ions converted H2O2 into HO by Fenton reaction. Meanwhile, rGO NSs mediated photothermal therapy (PTT) could further kill cancer cells. High temperature caused by photothermal conversion increased Fenton reaction rate, which enhanced the efficiency of MnO2 NPs mediated chemodynamic therapy (CDT). Importantly, thanks to the enhanced cell uptake of MnO2 NPs favored by the delivery properties of rGO, rGO@MnO2 possessed higher lethality to cancer cells. The decrease in the nanomaterials’ effective dose would further improve biosecurity and reduce cost. Therefore, rGO@MnO2 have great potential in cancer therapy by exploiting the synergistic effect of PTT and photothermal/delivery effect enhanced CDT.

Graphene oxide (GO) is currently developed for biomedical applications as a promising nanoplatform for drug delivery, phototherapy, and biosensing. As a consequence, its safety and cytotoxicity issues have attracted extensive attention. It has been demonstrated that GO causes an increase of intracellular oxidative stress, likely leading to its cytotoxicity and inhibition of cell proliferation. Being one of the main reductive intracellular substances, glutathione (GSH) is vital in the regulation of the oxidative stress level to maintain normal cellular functions. In this study, we found that GSH could be oxidized to GSSG by GO, leading to the formation of reduced GO (rGO). GSH depletion affects the intracellular reductive/oxidative balance, provoking the increase of the reactive oxygen species level, sequentially inhibiting cell viability and proliferation. Therefore, the reaction between GO and GSH provides a new perspective to explain the origin of GO cytotoxicity.

The coupled process of osteogenesis-angiogenesis plays a crucial role in periodontal tissue regeneration. Although various cytokines or chemokines have been widely applied in periodontal in situ tissue engineering, most of them are macromolecular proteins with the drawbacks of short effective half-life, poor stability and high cost, which constrain their clinical translation. Our study aimed to develop a difunctional structure for periodontal tissue regeneration by incorporating an angiogenic small molecule, dimethyloxalylglycine (DMOG), and an osteoinductive inorganic nanomaterial, nanosilicate (nSi) into poly (lactic-co-glycolic acid) (PLGA) fibers by electrospinning. The physiochemical properties of DMOG/nSi-PLGA fibrous membranes were characterized. Thereafter, the effect of DMOG/nSi-PLGA membranes on periodontal tissue regeneration was evaluated by detecting osteogenic and angiogenic differentiation potential of periodontal ligament stem cells (PDLSCs) in vitro. Additionally, the fibrous membranes were transplanted into rat periodontal defects, and tissue regeneration was assessed with histological evaluation, micro-computed tomography (micro-CT), and immunohistochemical analysis. DMOG/nSi-PLGA membranes possessed preferable mechanical property and biocompatibility. PDLSCs seeded on the DMOG/nSi-PLGA membranes showed up-regulated expression of osteogenic and angiogenic markers, higher alkaline phosphatase (ALP) activity, and more tube formation in comparison with single application. Further, in vivo study showed that the DMOG/nSi-PLGA membranes promoted recruitment of CD90+/CD34− stromal cells, induced angiogenesis and osteogenesis, and regenerated cementum-ligament-bone complex in periodontal defects. Consequently, the combination of DMOG and nSi exerted admirable effects on periodontal tissue regeneration. DMOG/nSi-PLGA fibrous membranes could enhance and orchestrate osteogenesis-angiogenesis, and may have the potential to be translated as an effective scaffold in periodontal tissue engineering., Graphical abstract Image 1, Highlights • Dual-load fibrous structure possessed preferable mechanical property and biocompatibility. • Fibrous structure can orchestrate and enhance osteogenesis-angiogenesis coupling. • Difunctional fibrous structure can recruit CD90+/CD34− stromal cells to periodontal defects. • Difunctional fibrous structure obtained functional periodontal tissue regeneration.

Graphene-related materials (GRMs) are subject to intensive investigations and considerable progress has been made in recent years in terms of safety assessment. However, limited information is available concerning the hazard potential of GRM-containing products such as graphene-reinforced composites. In the present study, we conducted a comprehensive investigation of the potential biological effects of particles released through an abrasion process from reduced graphene oxide (rGO)-reinforced composites of polyamide 6 (PA6), a widely used engineered thermoplastic polymer, in comparison to as-produced rGO. First, a panel of well-established in vitro models, representative of the immune system and possible target organs such as the lungs, the gut, and the skin, was applied. Limited responses to PA6-rGO exposure were found in the different in vitro models. Only as-produced rGO induced substantial adverse effects, in particular in macrophages. Since inhalation of airborne materials is a key occupational concern, we then sought to test whether the in vitro responses noted for these materials would translate into adverse effects in vivo. To this end, the response at 1, 7 and 28 days after a single pulmonary exposure was evaluated in mice. In agreement with the in vitro data, PA6-rGO induced a modest and transient pulmonary inflammation, resolved by day 28. In contrast, rGO induced a longer-lasting, albeit moderate inflammation that did not lead to tissue remodeling within 28 days. Taken together, the present study suggests a negligible impact on human health under acute exposure conditions of GRM fillers such as rGO when released from composites at doses expected at the workplace., This work was supported by the European Union (EU) 8th Framework Program for Research and Technological Development, Graphene Flagship project (H2020-FET- GrapheneCore2 - #785219 and H2020-FET- GrapheneCore3 - #881603). Part of this work was supported by the University of Trieste, the Agence Nationale de la Recherche (ANR) through the LabEx project Chemistry of Complex Systems (ANR-10-LABX- 0026_CSC), the Maria de Maeztu Units of Excellence Program from the Spanish State Research Agency – Grant No. MDM-2017-0720 and the Swiss National Science Foundation (Grant 310030_169207).

During wound healing, bacterial infection is one of the main limiting factors for the desired efficiency. Wound dressing-mediated antibiotics therapies could overcome this problem to a great extent due to sustained drug release and controllable dose. Here, we designed a kind of alginate injectable hydrogel loaded with minocycline (SA@MC) as a dressing for staphylococcus aureus-infected wound healing. SA@MC hydrogel possessed good injectability and can be injected by syringes. MC participated in the gel formation, causing the microstructure change based on the morphology characterization. The element mapping and FT-IR spectra further confirmed the successful loading of MC in SA hydrogel. Interestingly, MC was released more efficiently in a weakly alkaline condition (pH 7–8) than in a weakly acidic condition (pH 4–6) from SA@MC injectable hydrogel, which means that there is an accelerated release to respond to the weakly alkaline wound microenvironment. Meanwhile, SA@MC injectable hydrogel had high biocompatibility and excellent antibacterial activity due to the sustained release of MC. Further, in vivo experiment results demonstrated that SA@MC injectable hydrogel promoted staphylococcus aureus-infected wound healing efficiently. In summary, the injectable composite hydrogel can serve as an ideal dressing to prevent bacterial infection and promote wound healing.

Neural stem cell (NSC)-based therapy holds great promise for the treatment of neurodegenerative diseases. Presently, however, it is hindered by poor functional neuronal differentiation. Electrical stimulation is considered one of the most effective ways to promote neuronal differentiation of NSCs. In addition to surgically implanted electrodes, traditional electrical stimulation includes wires connected to the external power supply, and an additional surgery is required to remove the electrodes or wires following stimulation, which may cause secondary injuries and infections. Herein, a novel method is reported for generation of wireless electrical signals on an Au nanostrip array by leveraging the effect of electromagnetic induction under a rotating magnetic field. The intensity of the generated electrical signals depends on the rotation speed and magnetic field strength. The Au nanostrip array-mediated electric stimulation promotes NSC differentiation into mature neurons within 5 days, at the mRNA, protein, and function levels. The rate of differentiation is faster by at least 5 days than that in cells without treatment. The Au nanostrip array-based wireless device also accelerates neuronal differentiation of NSCs in vivo. The novel method to accelerate the neuronal differentiation of NSCs has the advantages of wireless, timely, localized and precise controllability, and noninvasive power supplementation.

International audience; Human health can be affected by materials indirectly through exposure to the environment or directly through close contact and uptake. With the ever-growing use of 2D materials in many applications such as electronics, medical therapeutics, molecular sensing, and energy storage, it has become more pertinent to investigate their impact on the immune system. Dendritic cells (DCs) are highly important, considering their role as the main link between the innate and the adaptive immune system. By using primary human DCs, it is shown that hexagonal boron nitride (hBN), graphene oxide (GO) and molybdenum disulphide have minimal effects on viability. In particular, it is evidenced that hBN and GO increase DC maturation, while GO leads to the release of reactive oxygen species and pro-inflammatory cytokines. hBN and MoS2 increase T cell proliferation with and without the presence of DCs. hBN in particular does not show any sign of downstream T cell polarization. The study allows ranking of the three materials in terms of inherent toxicity, providing the following trend: GO > hBN ≈ MoS2, with GO the most cytotoxic.

Nanostructured hydroxyapatite (HAp) has been applied widely as a scaffold material for bone tissue engineering for its good osteoinduction and biodegradability. However, the degradation process and the distribution of degraded HAp within the bone-defect cavity is still not clear. To visually study the behavior of HAp in bone repair process, a membrane of HAp/terbium (Tb)-HAp nanowires (NWs) was prepared with a concentric circle structure (CCS), of which the inner circle and the outer ring were constructed with Tb-HAp and HAp NWs, respectively. HAp/Tb-HAp CCS membrane possessed good osteogenic capacity and efficient fluorescence in the center for visualization. The in vitro experimental results proved that the Tb-HAp and HAp NWs membranes both presented high cytocompatibility and adequate efficiency to induce osteogenic differentiation of bone marrow stem cells (BMSCs). HAp/Tb-HAp CCS membranes were then implanted into a rat calvarial bone-defect model to study the behavior of HAp in bone repair process in vivo by tracking the fluorescence distribution. The results showed that the fluorescence of Tb-HAp diffused gradually from the inner circle to the outer ring, which suggested that the HAp was first degraded, and then the degraded product was diffused and finally reconstructed. Further, the histological results proved that the doping of Tb did not impair the promotive effect of HAp on bone repair process. Therefore, this study provided a visual method to observe the degradation-diffusion-reconstruction behavior of HAp nanomaterials in bone repair process. Statement of significance The study of dynamic degradation process of implanted hydroxyapatite (HAp) materials in bone-defect cavity is of great significance to bone tissue engineering applications. Here, we designed a HAp/Tb-HAp nanowires (NWs) membrane with concentric circle structure (CCS) to visibly observe the behavior of HAp during bone repair process. HAp/Tb-HAp CCS membrane possessed both osteoinduction ability and fluorescence property. Calvarial bone-defect repair experiments in vivo showed that the fluorescence of Tb-HAp diffused gradually from inner circle to outer ring, which suggested that HAp was first degraded, then diffused and finally reconstructed. Therefore, this invention provides not only a visible method to observe the degradation-diffusion-reconstruction behavior of HAp-based biomaterials, but also a basic understanding of the dynamic change of HAp-based biomaterials.

Directed differentiation enables the production of a specific cell type by manipulating signals in development. However, there is a lack of effective means to accelerate the regeneration of neurons of particular subtypes for pathogenesis and clinical therapy. In this study, we find that hydroxyapatite (HAp) nanorods promote neural differentiation of neural stem cells due to their chemical compositions. Lysosome-mediated degradation of HAp nanorods elevates intracellular calcium concentrations and accelerates GABAergic neurogenesis. As a mechanism, the enhanced activity of a Ca

Existing local drug delivery systems for periodontitis suffer from poor antibacterial effect and unsatisfied periodontal regeneration. In this study, a smart gingipain-responsive hydrogel (PEGPD@SDF-1) was synthesized as an environmentally sensitive carrier for on-demand drug delivery. The PEGPD@SDF-1 hydrogel was synthesized from polyethylene glycol diacrylate (PEG-DA) based scaffolds, dithiothreitol (DTT), and a novel designed functional peptide module (FPM) via Michael-type addition reaction, and the hydrogel was further loaded with stromal cell derived factor-1 (SDF-1). The FPM exhibiting a structure of anchor peptide-short antimicrobial peptide (SAMP)-anchor peptide could be cleaved by gingipain specifically, and the SAMP was released out of the hydrogel for antibacterial effect in response to gingipain. The hydrogel properties were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), swelling ratio analysis, degradation evaluation, and release curve description of the SAMP and SDF-1. Results

In the last years, cancer immunotherapy has started to attract a lot of attention, becoming one of the alternatives in the clinical treatment of cancer. Indeed, one of the advantages of immunotherapy is that both primary and distant tumors can be efficiently eradicated through a triggered immune response. Due to their large specific surface area and unique physicochemical properties, 2D materials have become popular in cancer immunotherapy, especially as efficient drug carriers. They have been also exploited as photothermal platforms, chemodynamic agents, and photosensitizers to further enhance the efficacy of the therapy. In this review, the focus is on the recent development of 2D materials as new tools to combine immunotherapy with chemotherapy, photothermal therapy, photodynamic therapy, chemodynamic therapy, radiotherapy, and radiodynamic therapy. These innovative synergistic approaches intend to go beyond the classical strategies based on a simple delivery function of immune modulators by nanomaterials. Furthermore, the effects of the 2D materials themselves and their surface properties (e.g., chemical modification and protein corona formation) on the induction of an immune response will be also discussed.

Proinflammatory (M1) macrophages play a vital role in antitumor immunity, and regulation of proinflammatory macrophage polarization is critical for immunotherapy. The polarization of macrophages can be regulated by biological or chemical stimulation, but investigations of the regulatory effect of physical stimulation are limited. Herein, regulating macrophage polarization with localized electrical signals derived from a piezoelectric β‐phase poly(vinylidene fluoride) (β‐PVDF) film in a wireless mode is proposed. Charges released on the surface of the β‐PVDF film driven by ultrasonic irradiation can significantly enhance the M1 polarization of macrophages. Mechanistic investigation confirms that electrical potentials rather than reactive oxygen species and mechanical forces enable Ca2+ influx through voltage‐gated channels and establishment of the Ca2+‐CAMK2A‐NF‐κB axis to promote the proinflammatory macrophage response during ultrasound treatment. Piezoelectric material‐mediated electrical signal‐activated proinflammatory macrophages significantly inhibit tumor cell proliferation. A method for electrogenetic regulation of immune cells as well as a powerful tool for engineering macrophages for immunotherapy is provided here., Regulating macrophage polarization with localized electrical signals derived from a piezoelectric β‐phase poly(vinylidene fluoride) (β‐PVDF) film in a wireless mode is proposed, providing a method for electrogenetic regulation of immune cells as well as a powerful tool for engineering macrophages for immunotherapy.

Severe bone defects, especially accompanied by vascular and peripheral nerve injuries, remain a massive challenge. Most studies related to bone tissue engineering have focused on osteogenic differentiation of mesenchymal stem cells (MSCs), and ignored the formation of blood vessels and nerves in the newly generated bone owing to the lack of proper materials and methodology for tuning stem cells differentiated into osteogenic, neuronal, and endothelial cells (ECs) in the same scaffold system. Herein, a nanocellulose-reinforced hybrid membrane with good mechanical properties and control over biodegradation by assembling ultralong hydroxyapatite nanobelts in a bacterial nanocellulose hydrogel is designed and synthesized. Osteogenic, neuronal cells are successfully differentiated on this hybrid membrane. Based on the multi-lineage differentiation property of the membrane, a bioactive 3D osteoid tissue (osteogenic, neural, and ECs) is mimetically constructed in vitro using layer-by-layer culture and integration. The bone regeneration ability of the as-prepared bioactive osteoid tissue is assessed in vivo via heterotopic osteogenesis experiments for eight weeks. The rapid new bone growth and formation of blood capillaries and nerve fibers prove that the hybrid membrane can be universally applied as a stem cell multi-lineage differentiation platform, which has significant applications in bone tissue engineering.

Objectives Articular cartilage plays a vital role in bearing and buffering. Injured cartilage and subchondral bone repair is a crucial challenge in cartilage tissue engineering due to the peculiar structure of osteochondral unit and the requirement of osteogenic/chondrogenic bi‐directional differentiation. Based on the bionics principle, a nanotextured silk fibroin (SF)‐chondroitin sulphate (CS)/hydroxyapatite (HAp) nanowire tough bilayer structure was prepared for osteochondral repair. Methods The SF‐CS/HAp membrane was constructed by alcohol‐induced β‐sheet formation serving as the physical crosslink. Its osteochondral repairing capacity was evaluated by culturing bone marrow mesenchymal stem cells (BMSCs) in vitro and constructing a rat osteochondral defect model in vivo. Results The bilayer SF‐CS/HAp membrane with satisfactory mechanical properties similar to natural cartilage imitated the natural osteochondral unit structural layers and exerted the function of bearing and buffering timely after in vivo implantation. SF‐CS layer upregulated the expression of chondrogenesis‐related genes of BMSCs by surface nanotopography and sustained release CS. Meanwhile, nanotextured HAp layer assembled with nanowire endowed the membrane with an osteogenic differentiation tendency for BMSCs. In vivo results proved that the biomimetic bilayer structure dramatically promoted new cartilage formation and subchondral bone remodelling for osteochondral defect model after implantation. Conclusions The SF‐CS/HAp biomimetic bilayer membrane provides a promising strategy for precise osteochondral repair., Nanotextured silk fibroin (SF)‐chondroitin sulphate (CS)/hydroxyapatite (HAp) nanowire membrane with biphasic structure and desired mechanical performances due to β‐sheet formation was prepared to enhance chondrogenic/osteogenic bi‐directional differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro and facilitate osteochondral repair in vivo.

A large number of graphene and other 2D materials are currently used for the development of new technologies, increasingly entering different industrial sectors. Interrogating the impact of such 2D materials on health and environment is crucial for both modulating their potential toxicity in living organisms and eliminating them from the environment. In this context, understanding if 2D materials are bio-persistent is mandatory. In this review we describe the importance of biodegradability and decomposition of 2D materials. We initially cover the biodegradation of graphene family materials, followed by other emerging classes of 2D materials including transition metal dichalcogenides and oxides, Xenes, Mxenes and other non-metallic 2D materials. We explain the role of defects and functional groups, introduced onto the surface of the materials during their preparation, and the consequences of chemical functionalization on biodegradability. In strong relation to the chemistry on 2D materials, we describe the concept of "degradation-by-design" that we contributed to develop, and which concerns the covalent modification with appropriate molecules to enhance the biodegradability of 2D materials. Finally, we cover the importance of designing new biodegradable 2D conjugates and devices for biomedical applications as drug delivery carriers, in bioelectronics, and tissue engineering. We would like to highlight that the biodegradation of 2D materials mainly depends on the type of material, the chemical functionalization, the aqueous dispersibility and the redox potentials of the different oxidative environments. Biodegradation is one of the necessary conditions for the safe application of 2D materials. Therefore, we hope that this review will help to better understand their biodegradation processes, and will stimulate the chemists to explore new chemical strategies to design safer products, composites and devices containing 2D materials.

MicroRNA (miRNA) has been reported to exert important functions in papillary thyroid carcinomas (PTC). However, the role of miRNA in aggressive PTC (APTC) remains unclear. Here, we investigated the diagnostic potentials and mechanisms of miR-221/222 in APTC. Results showed that miR-221/222 were markedly up-regulated in PTC, compared with the adjacent normal tissue (ANT). A high expression of miR-221/222 were associated with a primary tumor, regional lymph node, and distant metastasis (TNM) stage, multicentricity, lymph node metastasis, and extra-thyroidal extension. Receiver operating characteristic (ROC) curve analysis indicated that miR-221/222 could be used as APTC diagnostic markers. Moreover, miR-221/222 tremendously promoted migration and invasion and inhibited apoptosis and autophagy in PTC cells. A luciferase assay showed that miR-221/222 inhibited the fluorescent activity of autophagy-related protein 10 (ATG10). Furthermore, miR-221/222 decreased ATG10 mRNA and protein levels. Silencing of ATG10 significantly abrogated the effect of miR-221/222 on apoptosis and autophagy. We suggested that miR-221/222 can promote migration and invasion, and inhibit autophagy and apoptosis by targeting ATG10 in APTC.

Stem cell differentiation plays a significant role in tissue repair and regeneration. The interaction between stem cells and physical signals mediated by materials has significant influence on the fate of stem cells. The utilization of the stimulation originating from material physical properties to promote stem cell differentiation is being developed and has attracted much attention. However, it is difficult to induce electric signals into tissues noninvasively. In this study, piezoelectric nylon-11 nanoparticles (nylon-11 NPs) with uniform morphology were synthesized in mass production by a simple anti-solvent method. The prepared nylon-11 NPs possessed efficient piezoelectricity and high cytocompatibility. Fluorescent OPDA-coated nylon-11 NPs could image dental pulp stem cells (DPSCs) well, which demonstrated that nylon-11 NPs can be endocytosed easily by DPSCs. With the assistance of ultrasound, nylon-11 NPs could promote the osteogenic differentiation of DPSCs efficiently in a noninvasive way. Meanwhile, nylon-11 NPs could also promote the osteogenic differentiation of DPSCs to a certain extent. Therefore, piezoelectric nylon-11 NPs with the assistance of ultrasound will have enormous potential in tissue engineering, especially in stem cell fate regulation by noninvasive stimulation. This indicates that nanomaterial-mediated physical signals can regulate stem cell differentiation efficiently.

Nanoformulations that can respond to the specific tumor microenvironment (TME), such as a weakly acidic pH, low oxygen, and high glutathione (GSH), show promise for killing cancer cells with minima...

Periodontitis is an inflammatory disease leading to tooth loss, alveolar bone absorption and disorder of masticatory function. Guided tissue regeneration (GTR) is one of the most common strategies for regeneration of lost periodontium. During surgical process, barrier membranes, and osteoinductive/osteoconductive materials should be placed, respectively, which may increase risks of infection, bleeding, and difficulty of operation. Here, we introduced a new kind of hydroxyapatite (HAp) nanowires modified polylactic acid (PLA) membrane to achieve barrier/osteoinduction dual functions. The physicochemical property measurements suggested the two sides of the composite membrane did not change after composition. Then a rat mandibular defect model was established to investigate barrier and osteoinductive effects of this composite membrane. After implantation, effects of functional cells engraftment and osteoinduction were detected by scanning electron microscope (SEM), histomorphometric measurement, immunohistochemical staining, and Micro-CT scanning. SEM images showed HAp side engrafted more cells than PLA side. The result of immunohistochemical staining suggested HAp/PLA promoted the expression of bone-related markers. Moreover, there were more newly formed bones with better quality in HAp/PLA group. Therefore, this composite membrane would be a promising biomaterial in tissue engineering for bone regeneration due to its barrier/osteoinduction dual functions. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3099-3110, 2018.

Controllable osteoinduction maintained in the original defect area is the key to precise bone repair. To meet the requirement of precise bone regeneration, a hydroxyapatite (HAp) nanobelt/polylactic acid (PLA) (HAp/PLA) Janus membrane has been successfully prepared in this study by coating PLA on a paper-like HAp nanobelt film by a casting-pervaporation method. The Janus membrane possesses dual functions: excellent osteoinduction from the hydrophilic HAp nanobelt side and barrier function originating from the hydrophobic PLA film. The cell viability and osteogenic differentiation ability of human adipose-derived stem cells (hADSCs) on the Janus membrane were assessed. The in vitro experimental results prove that the HAp nanobelt side presents high cell viability and efficient osteoinduction without any growth factor and that the PLA side can prohibit cell attachment. The in vivo repair experiments on a rat mandible defect model prove that the PLA side can prevent postoperative adhesion between bone and adjacent soft tissues. Most importantly, the HAp side has a strong ability to promote defect repair and bone regeneration. Therefore, the HAp/PLA Janus membrane will have wide applications as a kind of tissue engineering material in precise bone repair because of its unique dual osteoinduction/barrier functions, biocompatibility, low cost, and its ability to be mass-produced. State of Significance Precise bone defect repair to keeping tissue integrity and original outline shape is a very important issue for tissue engineering. Here, we have designed and prepared a novel HAp/PLA Janus membrane using a casting-pervaporation method to form a layer of PLA film on paper-like HAp nanobelt film. HAp nanobelt side of the Janus membrane can successfully promote osteogenic differentiation. PLA side of the Janus membrane exhibits good properties as a barrier for preventing the adhesion of cells in vitro. Mandible repair experiments in vivo have shown that the HAp/PLA Janus membrane can promote rat mandible repair on the HAp side and can successfully prevent postoperative adhesion on the PLA side at the same time. Therefore, the HAp/PLA Janus membrane with its osteoinduction/barrier dual functions can be applied to repair bone defect precisely.

In this work, we designed a simple and low cost acid-dissolved/alkali-solidified self-sphering shaping method (AASS) to automatically fabricate three-dimension (3D) stem cell expansion microsphere scaffolds in large scale to satisfy the urgent need for stem cells in tissue engineering and clinical medicine research. We chose chitosan as the main part of microsphere scaffold, graphene oxide of 3 wt% as the strength agent, and genipin as the fluorescence generator to fabricate fluorescent chitosan (CS)/graphene oxide (GO) hybrid microspheres. The diameters of the hybrid microspheres are about 400 μm with the diameter error less than 10%, which is suitable for stem cells spreading. These hybrid microspheres with good biocompatibility can support the cells’ spread, growth and proliferation. After cultured for 5 days, the total number of cells on microspheres has almost increased fourfold. Most importantly, the microspheres can maintain the cell type. After cultured for 7 days, almost all cells still express main markers of human umbilical cord mesenchymal stem cells (HUMSCs). The hybrid microspheres can support long-time stem cell expansion because of their good mechanical strength, controllable degradability, and low expansion rate when soaked in media. Furthermore, their autofluorescence also makes observing and tracking the stem cells behavior on surface of microsphere scaffolds more convenient. This research provides a powerful method for mass-producing chitosan/graphene oxide hybrid microspheres for 3D stem cells expansion. This method is easy to be put into industrial production, and may have tremendous value in medicinal and clinical applications.

It is well-accepted that most osteogenic differentiation processes do need growth factors assistance to improve efficiency. As a material cue, hydroxyapatite (HAp) can promote osteogenic differentiation of stem cells only in a way. Up to now, rare work related to the relationship between HAp nanostructures and stem cells in osteogenic differentiation process without the assistance of growth factors has been reported. In this study, one-dimensional (1D) HAp nanostructures with tunable length were synthesized by an oleic acid assisted solvothermal method by adjusting the alcohol/water ratio (η). The morphology of 1D HAp nanostructures can be changed from long nanowires into nanorods with the η value change. Different substrates constructed by 1D HAp nanostructures were prepared to investigate the effect of morphology of nanostructured HAp on stem cell fate without any growth factors or differentiation induce media. Human adipose-derived stem cells (hADSCs), a kind of promising stem cell for autologous stem cell tissue engineering, were used as the stem cell model. The experiments prove that HAp morphology can determine the performance of hADSCs cultured on different substrates. Substrate constructed by HAp nanorods (100 nm) is of little benefit to osteogenic differentiations. Substrate constructed on HAp long nanowires (50 μm) causes growth and spread inhibition of hADSCs, which even causes most cells death after 7 days of culture. However, substrate constructed by HAp short nanowires (5 μm) can destine the hADSCs differentiation to osteoblasts efficiently in normal medium (after 3 weeks) without any growth factors. It is surprise that hADSCs have changed to polyhedral morphology and exhibited the tendency to osteogenic differentiation after only 24 h culture. Hydroxyapatite nanostructures mediated stem cell osteogenic differentiation excluding growth factors provides a powerful cue to design biomaterials with special nanostructures, and helps to elucidate the interaction of stem cell and biomaterials nanostructures. The results from this study are promising for application in bone tissue engineering.

Conventional electrochemical polymerization is performed on electrodes driven by a direct current power source. It is impossible to realize an electrochemical polymerization reaction on the surfaces of individual nanocrystals in an aqueous system due to the difficulty of connecting all of the nanocrystals to a power source with wires or with the aid of microfabrication, especially in the environment of liquid. In this work, a micro pseudo-electrochemical polymerization reaction was proposed for in situ synthesis of polyaniline (PANI) on the surface of BaTiO 3 nanocubes to form BaTiO 3 @PANI core-shell nanocubes. The electric potential of the micro pseudo-electrochemical polymerization originates from the opposite spontaneous polarized charges on the surface of a pair of adjacent BaTiO 3 nanocubes, which form a micro-scale electrochemical cell in reaction solution. Based on the piezotronic effect of the BaTiO 3 nanocubes, ultrasonic excitation was introduced to renew the piezoelectric charges on the surfaces of the BaTiO 3 nanocubes, and enhance the polymerization reaction. The ferroelectric electric potential and piezotronic effect-induced micro pseudo-electrochemical reactions can also be used in other nanomaterials-based electrochemical applications, such as micro-electrochemical water splitting, micro-electrophotocatalysis, and ultrasonic therapy.

The fate of stem cells at the single cell level with limited communication with other cells is still unknown due to the lack of an efficient tool for highly accurate molecular detection. Moreover, the conditional sensitivity of biological experiments requires a sufficient number of parallel experiments to support a conclusion. In this work, a microfluidic single cell chip is designed for use with a protein chip to investigate the effect of hydroxyapatite (HAp) on the osteogenic differentiation of human adipose-derived stem cells (hADSCs) in situ at the single cell level. By successfully detecting secretory proteins in situ, it is found that the HAp nanorods enhance osteogenic differentiation at the single cell level. In the chip, the single cell seeding approach confirms the osteogenic differentiation of the hADSCs, which endocytoses HAp, by reducing the influence of the factors secreted by neighboring differentiating cells. Most importantly, more than 7000 microchambers provide a sufficient number of parallel experiments for statistical analysis, which ensure a high level of repeatability of the HAp nanorod-induced osteogenic differentiation. The microfluidic chip comprising single cell culture microchambers with in situ detection capability is a promising tool for research on cell behavior or cell fate at the single cell level.

The interaction event between programmed death receptor-1 (PD-1) and its ligand (PD-L1) functions as an essential immune checkpoint against cytotoxic T effector cell activation. Previously, a number of small-molecule inhibitors and antibody drugs have been successfully developed to block the PD1/PDL1 signaling axis for breast cancer immunotherapy. Here, we attempt to directly disrupt the formation of PD-1/PD-L1 complex by using a self-inhibitory peptide (SIP) strategy. In the procedure, the complex crystal structure is examined systematically with energetic analysis and alanine scanning. Two double-stranded segments I and II in PD-L1 active finger are identified as hotspot regions; they directly interact with the amphipathic pocket of PD-1 to form the complex system. The segments are derived from PD-L1 to define two SIP peptides, namely, DS-I and DS-II, which are thought to have capability of rebinding at the complex interface, thus disrupting PD-1/PD-L1 interaction as a new immune checkpoint blockade. A further analysis reveals that the free linear DS-I and DS-II peptides are highly flexible without protein context support, which would incur a large entropy penalty (unfavorable indirect readout effect) when rebinding to PD-1. Next, intramolecular cyclization is applied to constraining the intrinsically disordered conformation of free DS-II peptide into native ordered double-stranded configuration, which can be substantiated by molecular dynamics simulation and circular dichroism spectroscopy. Several cyclized counterparts of linear DS-II peptide are designed and their affinities to PD-1 are determined using fluorescence polarization assays. As might be expected, three designed cyclic peptides DS-II[c111–127], ΔDS-II[c111–127] and ΔDS-II[c110–128] exhibit considerably increased potency (Kd = 28.0 ± 4.2, 17.5 ± 3.1 and 11.6 ± 2.3 μM, respectively) relative to linear DS-II peptide (Kd = 109 ± 15 μM).

Bone repair is a complex and multifactorial regulatory process, and achieving precise and efficient bone regeneration is a fundamental goal of bone tissue engineering. Promoting the synergistic effects of cell recruitment, immunomodulation, angiogenesis, and osteogenesis is a feasible strategy to augment bone repair. In this work, the multifunctional agent stromal cell-derived factor-1 (SDF-1) was loaded onto hydroxyapatite (HAp) nanowires and observed to endow HAp/polylactic acid (PLA) (HP) membrane with versatile capabilities for efficient guided bone regeneration. After being loaded onto HAp nanowires by physical and electrostatic adsorption, SDF-1 showed a relatively rapid release during the early period of bone regeneration and a slow-release during the later period. At the initial stage of bone repair, the SDF-1-HAp/PLA (S-HP) membrane promoted endogenous cell recruitment and macrophage M2 polarization. Later, the S-HP membrane facilitated vessel formation and finally enhanced mature bone regeneration. Therefore, the S-HP membrane could efficiently promote precise and oriented bone tissue regeneration through its synergistic multifunctional effects, demonstrating that this scaffold possesses great potential in guided tissue regeneration and provides guidance for the design of other functional biomaterials.