Jiangqi Pingxiao formula regulates dendritic cell apoptosis in an autophagy-dependent manner through the AMPK/mTOR pathway in a murine model of OVA-induced asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: Allergic asthma is a recurring respiratory condition that typically manifests during childhood or adolescence. It is characterized by a dominant type II immune response triggered by the identification and capturing of inhaled allergens by dendritic cells (DCs). Jiangqi Pingxiao Formula (JQPXF), a prescription medicine used for the treatment of pediatric asthma, has been clinically proven to be both safe and effective. However, its mechanism of action in the treatment of asthma has not been fully been fully elucidated. Recent research suggests that several natural compounds have the potential to target dendritic cells (DCs) and alleviate ovalbumin (OVA)-induced asthma, which may also be found within JQPXF. AIM OF THE STUDY: This study aimed to elucidate the effect of JQPXF on OVA-induced asthma model and its molecular mechanism targeting DCs. MATERIALS AND METHODS: The main constituents of JQPXF were analyzed by ultra performance liquid chromatography (UPLC). An asthma model was established by OVA. Hematoxylin-eosin staining and measurement of respiratory function was used to evaluate the treatment effect of JQPXF on asthmatic mice. Cytokine (IL-5, IL-13 and IgE) concentrations were determined by enzyme-linked immunosorbent assay (ELISA). Flow cytometry was employed to evaluate inflammatory cell infiltration (T helper 2 cells and DCs) in vivo and DC survival in vivo and vitro. Western blot and immunofluorescence were used to verify the molecular mechanisms. RESULTS: The results suggest that JQPXF can ameliorate pathological conditions and improve lung function in asthmatic mice, as well as the Th2 cells. Treatment with JQPXF significantly reduced the number of DCs and increased the number of Propidium iodide+ (PI) DCs. Furthermore, JQPXF upregulated protein levels of the pro-apoptotic factors Cleaved-caspase-3 and Bax, while downregulating the anti-apoptotic factor Bcl-2. Simultaneously, JQPXF increased autophagy levels by facilitating p62 degradation and promoting translation from LC3B I to LC3B II of DCs in vitro, as well as reducing the integrated optical density (IOD) of p62 within the CD11c-positive area in the lung. 3-Methyladenine (3-MA) was used to block autophagic flux and the apoptotic effect of JQPXF on DCs was abolished in vitro, with the number of DCs decreased by JQPXF being reversed in vivo. We further investigated the upstream key regulator of autophagy, the AMPK/mTOR pathway, and found that JQPXF increased AMPK phosphorylation while decreasing mTOR phosphorylation levels. Additionally, we employed Compound C (CC) as an AMPK inhibitor to inhibit this signaling pathway, and our findings revealed that both autophagic flux and apoptotic levels in DCs were abolished in vitro. CONCLUSIONS: In summary, we have demonstrated that JQPXF could alleviate type II inflammation in an asthmatic model by promoting the apoptosis of DCs through an autophagy-dependent mechanism, achieved by regulating the AMPK/mTOR signaling pathway.

Drug-loaded mucoadhesive microneedle patch for the treatment of oral submucous fibrosis.

Oral submucous fibrosis is a chronic, inflammatory and potentially malignant oral disease. Local delivery of triamcinolone to lesion site is a commonly used therapy. The existing methods for local drug delivery include topical administration and submucosal injection. However, in the wet and dynamic oral microenvironment, these methods have drawbacks such as limited drug delivery efficiency and injection pain. Therefore, it is urgently needed to develop an alternative local drug delivery system with high efficiency and painlessness. Inspired by the structure of band-aid, this study proposed a novel double-layered mucoadhesive microneedle patch for transmucosal drug delivery. The patch consisted of a mucoadhesive silk fibroin/tannic acid top-layer and a silk fibroin microneedle under-layer. When applying the annealing condition for the medium content of ß-sheets of silk fibroin, the microneedles in under-layer displayed both superior morphology and mechanical property. The mechanical strength of per needle (0.071N) was sufficient to penetrate the oral mucosa. Sequentially, the gelation efficiency of silk fibroin and tannic acid in top-layer was maximized as the weight ratio of tannic acid to silk fibroin reached 5:1. Moreover, in vitro results demonstrated the double-layered patch possessed undetectable cytotoxicity. The sustained release of triamcinolone was observed from the double-layered patch for at least 7 days. Furthermore, compared with other commercial buccal patches, the double-layered patch exhibited an enhanced wet adhesion strength of 37.74 kPa. In addition, ex vivo mucosal tissue penetration experiment confirmed that the double-layered patch could reach the lamina propria, ensuring effective drug delivery to the lesion site of oral submucous fibrosis. These results illustrate the promising potential of the drug-loaded mucoadhesive microneedle patch for the treatment of oral submucous fibrosis.

Immunomodulatory zinc-based materials for tissue regeneration.

Zinc(Zn)-based materials have contributed greatly to the rapid advancements in tissue engineering. The qualities they possess that make them so beneficial include their excellent biodegradability, biocompatibility, anti-bacterial activity, among and several others. Biomedical materials that act as a foreign body, will inevitably cause host immune response when introduced to the human body. As the osteoimmunology develops, the immunomodulatory characteristics of biomaterials have become an appealing concept to improve implant-tissue interaction and tissue restoration. Recently, Zn-based materials have also displayed immunomodulatory functions, especially macrophage polarization states. It can promote the transformation of M1 macrophages into M2 macrophages to enhance the tissue regeneration and reconstruction. This review covers mainly Zn-based materials and their characteristics, including metallic Zn alloys and Zn ceramics. We highlight the current advancements in the type of immune responses, as well as the mechanisms, that are induced by Zn-based biomaterials, most importantly the regulation of innate immunity and the mechanism of promoting tissue regeneration. To this end, we discuss their applications in biomedicine, and conclude with an outlook on future research challenges.

Administration methods of lipid-based nanoparticle delivery systems for cancer treatment.

As nano medications have developed in the recent four decades, nano-delivery systems have been applied in treating various diseases and are especially common in cancer treatment. Nano-delivery systems could target cancer-associated cells, enhance the accuracy and efficacy of treatment, and reduce systemic side effects. Among the many drugs on nano-carriers, the load system of lipid-based nanoparticles has the brightest prospect due to the high level of biocompatibility, biodegradability, loading capability, and immunogenicity. Previous reviews have comprehensively introduced their effects and progress. However, most of them did not provide great attention to practical applications. This article will focus on different intake methods, which decide the biological process of drugs. This suggests that we can modify lipid-based nano-delivery systems according to how they are capable of prolonging the half-life span and magnifying therapy effects in treating cancer. Besides, we put forth the problems that should be further studied in the future and their probable solutions.

Prognosis-related molecular subtyping in head and neck squamous cell carcinoma patients based on glycolytic/cholesterogenic gene data.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) remains an unmet medical challenge. Metabolic reprogramming is a hallmark of diverse cancers, including HNSCC. METHODS: We investigated the metabolic profile in HNSCC by using The Cancer Genome Atlas (TCGA) (n = 481) and Gene Expression Omnibus (GEO) (n = 97) databases. The metabolic stratification of HNSCC samples was identified by using unsupervised k-means clustering. We analyzed the correlations of the metabolic subtypes in HNSCC with featured genomic alterations and known HNSCC subtypes. We further validated the metabolism-related subtypes based on features of ENO1, PFKFB3, NSDHL and SQLE expression in HNSCC by Immunohistochemistry. In addition, genomic characteristics of tumor metabolism that varied among different cancer types were confirmed. RESULTS: Based on the median expression of coexpressed cholesterogenic and glycolytic genes, HNSCC subtypes were identified, including glycolytic, cholesterogenic, quiescent and mixed subtypes. The quiescent subtype was associated with the longest survival and was distributed in stage I and G1 HNSCC. Mutation analysis of HNSCC genes indicated that TP53 has the highest mutation frequency. The CDKN2A mutation frequency has the most significant differences amongst these four subtypes. There is good overlap between our metabolic subtypes and the HNSCC subtype. CONCLUSION: The four metabolic subtypes were successfully determined in HNSCC. Compared to the quiescent subtype, glycolytic, cholesterogenic and mixed subtypes had significantly worse outcome, which might offer guidelines for developing a novel treatment strategy for HNSCC.

Absolute bioavailability, dose proportionality, and tissue distribution of rotundic acid in rats based on validated LC-QqQ-MS/MS method.

Rotundic acid (RA), an ursane-type pentacyclic triterpene acid isolated from the dried barks of Ilex rotunda Thunb. (Aquifoliaceae), possesses diverse bioactivities. To further study its pharmacokinetics, a simple and sensitive liquid chromatography with triple quadrupole mass spectrometry (LC-QqQ-MS/MS) method was developed and validated to quantify RA concentration in rat plasma and tissue using etofesalamide as an internal standard (IS). Plasma and tissue samples were subjected to one-step protein precipitation. Chromatographic separation was achieved on a ZORBAX Eclipse XDB-C18 column (4.6 mm × 50 mm, 5 µm) under gradient conditions with eluents of methanol:acetonitrile (1:1, V/V) and 5 mM ammonium formate:methanol (9:1, V/V) at 0.5 mL/min. Multiple reaction monitoring transitions were performed at m/z 487.30 → 437.30 for RA and m/z 256.10 → 227.10 for IS in the negative mode. The developed LC-QqQ-MS/MS method exhibited good linearity (2-500 ng/mL) and was fully validated in accordance with U.S. Food and Drug Administration bioanalytical guidelines. Dose proportionality and bioavailability in rats were determined by comparing pharmacokinetic data after single oral (10, 20, and 40 mg/kg) and intravenous (10 mg/kg) administration of RA. Tissue distribution was studied following oral administration at 20 mg/kg. The results showed that the absolute bioavailability of RA after administration at different doses ranged from 16.1% to 19.4%. RA showed good dose proportionality over a dose range of 10-40 mg/kg. RA was rapidly absorbed in a dose-dependent manner and highly distributed in the liver. In conclusion, this study is the first to systematically elucidate the absorption and distribution characteristics of RA in rats, which can provide additional information for further development and evaluation of RA in drug metabolism and pharmacokinetic studies.

Nano-AgCu Alloy on Wood Surface for Mold Resistance.

The mold infection of wood reduces the quality of its surface and potentially endangers human health. One category of the most popular mold inhibitors on the market is water-soluble fungicides. However, easy leaching due to ionic forms is a problem, which reduces the effectiveness of their antimicrobial action, as well as causing environmental pollution. Interestingly, nanometer-sized sterilizing agents present strong permeability and highly fungicidal behavior, and they are not easily leached, due to the unique nanoscale effect, and they have become alternative candidates as marketable anti-mold agents for wood protection. In this study, we first designed and explored a nanoscale alloy (nano silver-copper alloy, nano-AgCu) to treat wood surfaces for mold growth resistance. The results showed that three molds, i.e., Aspergillus niger, Penicillium citrinum and Trichoderma viride, mainly grew on the surface of wood within a depth of 100 µm; and that the nano-AgCu alloy with a particle size of ~15 nm presented improved retention and anti-mold efficiency at a nanomaterial concentration on the wood surface. Its leaching rate increased non-linearly with the increase in nano-AgCu retention and then it showed a gradually decreasing trend. When the concentration reached 1000 mg/L, the nano-AgCu alloy uniformly distributed on the wood surface in a monodispersed state and exhibited a lower retention of 0.342 g/m2, with an anti-mold efficiency of more than 75% and a leaching rate of only 7.678%. Such results positioned 1000 mg/L as the toxic threshold concentration of nano-AgCu against the three molds. This study can provide a scientific basis for the analysis of the anti-mold mechanisms of nano-AgCu alloy on wood surfaces and guide the application of nano-metal alloy materials in the field of wood antimicrobials.

Biomimetic hierarchical implant surfaces promote early osseointegration in osteoporotic rats by suppressing macrophage activation and osteoclastogenesis.

Successful implant-bone integration remains a formidable challenge in osteoporotic patients, because of excessive inflammatory reactions and osteoclastogenesis around the peri-implant bone tissue. This study designed biomimetic micro/sub-micro hierarchical surfaces on titanium implants based on natural bone hierarchical structures to mitigate macrophage-mediated inflammatory reactions, osteoclastogenesis, and osteogenesis in vitro, as well as promote early osseointegration in vivo. It was found that the biomimetic hierarchical surfaces inhibited M1 macrophage-mediated inflammatory reactions via suppression of the TLR2/NF-κB signaling pathway in vitro. Subsequently, osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) was observed to be significantly enhanced on hierarchical surfaces in the presence of macrophage conditional media. Furthermore, osteoclast formation was also decreased by inhibiting the osteoclastogenesis regulatory factor NFATc-1 expression on hierarchical surfaces. In vivo, the implant with a micro/sub-micro hierarchical surface underwent rapid and early osseointegration, with the newly formed bone being tightly integrated with the implants. Hence, the hierarchical surface mitigated the inflammatory microenvironment around the implant, thereby inhibiting osteoclastogenesis. This study thus offers a novel biomimetic strategy for designing surface hierarchical topography to facilitate implant-bone osseointegration in osteoporotic patients.

Leachability and Anti-Mold Efficiency of Nanosilver on Poplar Wood Surface.

Water-based antimicrobial agents, used in environmentally friendly applications, are widely used in wood protection industries. Furthermore, nanomaterials as antimicrobial agents, because of their biocidal component, huge specific surface area, and unique nanoscale effect, have attracted attention in the field of biodurability. We employed aqueous dispersed nano-silver with a diameter of 10 nm~20 nm to treat poplar wood and evaluated its leaching resistance and anti-mold effect on the wood surface. The results revealed that the higher the retention of the nano-silver, the stronger the protection efficiency of the wood surface against three molds (Aspergillus niger V. Tiegh, Penicillium citrinum Thom, and Trichoderma viride Pers. ex Fr); and the leachability of the nano-silver presented a slowly growing trend with the increase in the retention. When the wood surface attained a silver retention of 0.324 g·m-2, its anti-mold efficiency against Aspergillus niger V. Tiegh, Penicillium citrinum Thom, and Trichoderma viride Pers. ex Fr reached 80, 75, and 80%, respectively, which achieved or even exceeded the required standard value of effective mold inhibition (75%). Notably, the nano-silver leaching rate at this retention attained merely 4.75 %. The nanoparticle, well distributed on a wood surface, may promote sufficient contact with fungi as well as strong interaction with wood cell wall components, which probably contributed to the effective anti-mold efficiency and the leaching resistance. This study provided positive evidence for the anti-mold effect of nano-silver on wood surface.

Circular RNA ITCH: An Emerging Multifunctional Regulator.

In the last decade, numerous circRNAs were discovered by virtue of the RNA-Seq technique. With the deepening of experimental research, circRNAs have brought to light the key biological functions and progression of human diseases. CircRNA ITCH has been demonstrated to be a tumor suppressor in numerous cancers, and recently it was found to play an important role in bone diseases, diabetes mellitus, and cardiovascular diseases. However, the functions of circ-ITCH have not been completely understood. In this review, we comprehensively provide a conceptual framework to elucidate circ-ITCH biological functions of cell proliferation, apoptosis and differentiation, and the pathological mechanisms of inflammation, drug resistance/toxicity, and tumorigenesis. Finally, we summarize its clinical applications in various diseases. This research aimed at clarifying the role of circ-ITCH, which could be a promising therapeutic target.

Research progress of azido-containing Pt(IV) antitumor compounds.

Cancer is a long-known incurable disease, and the medical use of cisplatin has been a significant discovery. However, the side-effects of cisplatin necessitate the development of new and improved drug. Therefore, in this study, we focused on the photoactivatable Pt(IV) compounds Pt[(X1)(X2)(Y1)(Y2)(N3)2], which have a completely novel mechanism of action. Pt(IV) can efficiently overcome the side-effects of cisplatin and other drugs. Here, we have demonstrated, summarized and discussed the effects and mechanism of these compounds. Compared to the relevant articles in the literature, we have provided a more detailed introduction and a made comprehensive classification of these compounds. We believe that our results can effectively provide a reference for the development of these drugs.

Current Status of Research on the Modification of Thermal Properties of Epoxy Resin-Based Syntactic Foam Insulation Materials.

As a lightweight and highly insulating composite material, epoxy resin syntactic foam is increasingly widely used for insulation filling in electrical equipment. To avoid core burning and cracking, which are prone to occur during the casting process, the epoxy resin-based syntactic foam insulation materials with high thermal conductivity and low coefficient of thermal expansion are required for composite insulation equipment. The review is divided into three sections concentrating on the two main aspects of modifying the thermal properties of syntactic foam. The mechanism and models, from the aspects of thermal conductivity and coefficient of thermal expansion, are presented in the first part. The second part aims to better understand the methods for modifying the thermal properties of syntactic foam by adding functional fillers, including the addition of thermally conductive particles, hollow glass microspheres, negative thermal expansion filler and fibers, etc. The third part concludes by describing the existing challenges in this research field and expanding the applicable areas of epoxy resin-based syntactic foam insulation materials, especially cross-arm composite insulation.

Restoration of electrical microenvironment enhances bone regeneration under diabetic conditions by modulating macrophage polarization.

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.

An overview on natural farnesyltransferase inhibitors for efficient cancer therapy.

As one of the world's five terminally ills, tumours can cause important genetic dysfunction. However, some current medicines for tumours usually have strong toxic side effects and are prone to drug resistance. Studies have found that farnesyltransferase inhibitors (FTIs) extracted from natural materials have a good inhibiting ability on tumours with fewer side effects. This article describes several FTIs extracted from natural materials and clarifies the current research progress, which provides a new choice for the treatment of tumours.

Screening of Nanocellulose from Different Biomass Resources and Its Integration for Hydrophobic Transparent Nanopaper.

Petroleum-based plastics, such as PP, PE, PVC, etc., have become an important source of environmental pollution due to their hard degradation, posing a serious threat to the human health. Isolating nanocellulose from abundant biomass waste resources and further integrating the nanocellulose into hydrophobic transparent film (i.e., nanopaper), to replace the traditional nondegradable plastic film, is of great significance for solving the problem of environmental pollution and achieving sustainable development of society. This study respectively extracted nanocellulose from the branches of Amorpha fruticosa Linn., wheat straw, and poplar residues via combined mechanical treatments of grinding and high-pressure homogenization. Among them, the nanocellulose derived from the Amorpha fruticosa has a finer structure, with diameter of about 10 nm and an aspect ratio of more than 500. With the nanocellulose as building block, we constructed hydrophilic nanopaper with high light transmittance (up to 90%) and high mechanical strength (tensile strength up to 110 MPa). After further hybridization by incorporating nano-silica into the nanopaper, followed by hydrophobic treatment, we built hydrophobic nanopaper with transmittance over 82% and a water contact angle of about 102° that could potentially replace transparent plastic film and has wide applications in food packaging, agricultural film, electronic device, and other fields.

Nanocellulose-Reinforced Polyurethane for Waterborne Wood Coating.

With the enhancement of people's environmental awareness, waterborne polyurethane (PU) paint-with its advantages of low release of volatile organic compounds (VOCs), low temperature flexibility, acid and alkali resistance, excellent solvent resistance and superior weather resistance-has made its application for wood furniture favored by the industry. However, due to its lower solid content and weak intermolecular force, the mechanical properties of waterborne PU paint are normally less than those of the traditional solvent-based polyurethane paint, which has become the key bottleneck restricting its wide applications. To this end, this study explores nanocellulose derived from biomass resources by the 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) oxidation method to reinforce and thus improve the mechanical properties of waterborne PU paint. Two methods of adding nanocellulose to waterborne PU-chemical addition and physical blending-are explored. Results show that, compared to the physical blending method, the chemical grafting method at 0.1 wt% nanocellulose addition results in the maximum improvement of the comprehensive properties of the PU coating. With this method, the tensile strength, elongation at break, hardness and abrasion resistance of the waterborne PU paint increase by up to 58.7%, ~55%, 6.9% and 3.45%, respectively, compared to the control PU; while the glossiness and surface drying time were hardly affected. Such exploration provides an effective way for wide applications of water PU in the wood industry and nanocellulose in waterborne wood coating.

Biomimetic piezoelectric nanocomposite membranes synergistically enhance osteogenesis of deproteinized bovine bone grafts.

Purpose: The combination of a bone graft with a barrier membrane is the classic method for guided bone regeneration (GBR) treatment. However, the insufficient osteoinductivity of currently-available barrier membranes and the consequent limited bone regeneration often inhibit the efficacy of bone repair. In this study, we utilized the piezoelectric properties of biomaterials to enhance the osteoinductivity of barrier membranes. Methods: A flexible nanocomposite membrane mimicking the piezoelectric properties of natural bone was utilized as the barrier membrane. Its therapeutic efficacy in repairing critical-sized rabbit mandible defects in combination with xenogenic grafts of deproteinized bovine bone (DBB) was explored. The nanocomposite membranes were fabricated with a homogeneous distribution of piezoelectric BaTiO3 nanoparticles (BTO NPs) embedded within a poly(vinylidene fluoridetrifluoroethylene) (P(VDF-TrFE)) matrix. Results: The piezoelectric coefficient of the polarized nanocomposite membranes was close to that of human bone. The piezoelectric coefficient of the polarized nanocomposite membranes was highly stable, with more than 90% of the original piezoelectric coefficient (d33) remaining up to 28 days after immersion in culture medium. Compared with commercially-available polytetrafluoroethylene (PTFE) membranes, the polarized BTO/P(VDF-TrFE) nanocomposite membranes exhibited higher osteoinductivity (assessed by immunofluorescence staining for runt-related transcription factor 2 (RUNX-2) expression) and induced significantly earlier neovascularization and complete mature bone-structure formation within the rabbit mandible critical-sized defects after implantation with DBB Bio-Oss® granules. Conclusion: Our findings thus demonstrated that the piezoelectric BTO/P(VDF-TrFE) nanocomposite membranes might be suitable for enhancing the clinical efficacy of GBR.

Electroactive BaTiO3 nanoparticle-functionalized fibrous scaffolds enhance osteogenic differentiation of mesenchymal stem cells.

It has been proven that the surface topographic cues of fiber arrangement can induce osteogenic differentiation of mesenchymal stem cells. However, this effect alone is weak and insufficient to meet the needs of regenerative medicine. In this work, electroactivity concept was introduced to enhance the osteoinductivity of fibrous scaffolds. The randomly oriented and aligned electroactive fibrous scaffolds of poly-(l-lactic acid) (PLLA) with incorporation of ferroelectric ceramic BaTiO3 (BTO) nanoparticles (NPs) were fabricated by electrospinning. Physicochemical properties, including fiber morphology, microstructure, composition, thermal stability, surface roughness, and surface wettability, of these fibrous scaffolds were studied. The dielectric properties of the scaffolds were evaluated. The results showed that the randomly oriented BTO/PLLA composite fibrous scaffolds had the highest dielectric permittivity of 1.19, which is of the same order of magnitude as the natural bone. The combined effects of fiber orientation and electrical activity on the osteogenic responses of bone marrow mesenchymal stem cells (BM-MSCs) were specifically investigated. Randomly oriented composite fibrous scaffolds significantly promoted polygonal spreading and encouraged early osteogenic differentiation in BM-MSCs, whereas aligned composite fibrous scaffolds promoted cell elongation and discouraged osteogenic differentiation. These results evidenced that randomly fiber orientation and biomimetic electric activity have combining effects on osteogenic differentiation of BM-MSCs. Our findings indicate that coupling effects of multi-physical properties should be paid more attention to mimic the microenvironment for enhancing osteogenic differentiation of BM-MSCs.

Nanocomposite Membranes Enhance Bone Regeneration Through Restoring Physiological Electric Microenvironment.

Physiological electric potential is well-known for its indispensable role in maintaining bone volume and quality. Although implanted biomaterials simulating structural, morphological, mechanical, and chemical properties of natural tissue or organ has been introduced in the field of bone regeneration, the concept of restoring physiological electric microenvironment remains ignored in biomaterials design. In this work, a flexible nanocomposite membrane mimicking the endogenous electric potential is fabricated to explore its bone defect repair efficiency. BaTiO3 nanoparticles (BTO NPs) were first coated with polydopamine. Then the composite membranes are fabricated with homogeneous distribution of Dopa@BTO NPs in poly(vinylidene fluoridetrifluoroethylene) (P(VDF-TrFE)) matrix. The surface potential of the nanocomposite membranes could be tuned up to -76.8 mV by optimizing the composition ratio and corona poling treatment, which conform to the level of endogenous biopotential. Remarkably, the surface potential of polarized nanocomposite membranes exhibited a dramatic stability with more than half of original surface potential remained up to 12 weeks in the condition of bone defect. In vitro, the membranes encouraged bone marrow mesenchymal stem cells (BM-MSCs) activity and osteogenic differentiation. In vivo, the membranes sustainably maintained the electric microenvironment giving rise to rapid bone regeneration and complete mature bone-structure formation. Our findings evidence that physiological electric potential repair should be paid sufficient attention in biomaterials design, and this concept might provide an innovative and well-suited strategy for bone regenerative therapies.

Effects of deer age on the physicochemical properties of deproteinized antler cancellous bone: an approach to optimize osteoconductivity of bone graft.

Inorganic bone xenograft materials have recently found extensive surgical application in the clinic. Previously we have demonstrated that calcinated antler cancellous bone (CACB) has great potential for bone defect repair, due to the similar structure and composition compared with human bone. However, the effect of intrinsic material characteristics, particularly deer age, on the physicochemical and biological properties of CACB scaffolds has not been clarified. The aim of this study is to investigate the structure, composition and in vitro solubility of CACB scaffolds derived from deer of varying ages, including young (CACB-Y), middle-aged (CACB-M), and old (CACB-O) deer, and to determine subsequent biological performance. Microstructural analyses showed looser crystal arrangement and lower porosity in CACB-M compared to CACB-Y and CACB-O. Phase-structure analysis showed that CACB-M had the largest crystal size. Component characterization results showed that CACB-M had the most carbonated substitute and the highest content of trace elements (Na, Fe). The in vitro solubility test showed that CACB-M had the fastest dissolution and apatite deposition rates with new crystalline phases. In addition, CACB-M could be conducive for attachment, proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells in vitro, as well as conducive for bone regeneration in vivo. These findings indicate that animal age should be seriously considered as a key parameter in optimizing the physicochemical and biological properties of deproteinized antler cancellous bone substitutes for bone regeneration applications.