Preparation of a novel antibacterial magnesium carbonate coating on a titanium surface and its in vitro biocompatibility.

Magnesium-based coatings have attracted great attention in surface modification of titanium implants due to their superior angiogenic and osteogenic properties. However, their biological effects as a carbonate-based constituent remain unrevealed. In this study, magnesium carbonate coatings were prepared on titanium surfaces under hydrothermal conditions and subsequently treated with hydrogen peroxide. Also, their antibacterial activity and in vitro cell biocompatibility were evaluated. The obtained coatings consisted of nanoparticles without cracks and exhibited excellent adhesion to the substrate. X-ray diffraction (XRD) results indicated pure magnesium carbonate coatings formed on the Ti surface after hydrothermal treatment. After hydrogen peroxide treatment, the phase composition of the coatings had no obvious change. Compared to the untreated coatings, the hydrogen peroxide-treated coatings showed increased surface roughness and hydrophilicity. Co-culture with Staphylococcus aureus (S. aureus) demonstrated that the obtained coatings had good antibacterial activity. In vitro cell culture results showed that the hydrogen peroxide-treated coatings enhanced the viability, proliferation, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). These findings suggest that this MgCO3-based coating exhibits excellent antibacterial performance and osteogenic potential. Based on the above, this study provides a simple method for preparing titanium implants with dual antibacterial and osteogenic capabilities, holding great promise in clinical applications.

Cell response and bone ingrowth to 3D printed Ti6Al4V scaffolds with Mg-incorporating sol-gel Ta2O5 coating.

In recent years, additive manufacturing techniques have been used to fabricate 3D titanium (Ti)-based scaffolds for production of desirable complex shapes. However, insufficient osteointegration of porous Ti-based scaffolds can elicit long-term complications (e.g., aseptic loosening) and need further revision surgery. In this study, a magnesium (Mg)-incorporating tantalum (Ta) coating was deposited on a 3D Ti6Al4V scaffold using a sol-gel method for enhancing its osteogenic properties. To evaluate the biofunction of this surface, bone mesenchymal stem cells and rabbit femoral condyle were used to assess the cell response and bone ingrowth, respectively. Ta2O5 coatings and Mg-incorporating Ta2O5 coatings were both homogeneously deposited on porous scaffolds. In vitro studies revealed that both coatings exhibit enhanced cell proliferation, ALP activity, osteogenic gene expression and mineralization compared with the uncoated Ti6Al4V scaffold. Especially for Mg-incorporating Ta2O5 coatings, great improvements were observed. In vivo studies, including radiographic examination, fluorochrome labeling and histological evaluation also followed similar trends. Also, bone ingrowth to scaffolds with Mg-incorporating Ta2O5 coatings exhibited the most significant increase compared with uncoated and Ta2O5 coated scaffolds. All the above results indicate that Mg-doped Ta2O5 coatings are an effective tool for facilitating osteointegration of conventional porous Ti6Al4V scaffolds.

Photoinduced Radical Persistent Luminescence in Semialiphatic Polyimide System with Temperature and Humidity Resistance.

Organic persistent luminescence (pL) systems with photoresponsive dynamic features have valuable applications in the fields of data encryption, anticounterfeiting, and bioimaging. Photoinduced radical luminescent materials have a unique luminous mechanism with the potential to achieve dynamic pL. It is extremely challenging to obtain radical pL under ambient conditions; on account of it, it is unstable in air. Herein, a new semialiphatic polyimide-based polymer (A0) is developed, which can achieve dynamic pL through reversible conversion of radical under photoexcitation. A "joint-donor-spacer-acceptor" molecular design strategy is applied to effectively modulate the intramolecular charge-transfer and charge-transfer complex interactions, resulting in effective protection of the radical generated under photoirradiation. Meanwhile, polyimide-based polymers of A1-A4 are obtained by doping different amine-containing fluorescent dyes to modulate the dynamic afterglow color from green to red via the triplet to singlet Förster resonance energy-transfer pathway. Notably, benefiting from the structural characteristics of the polyimide-based polymer, A0-A4 have excellent processability, thermal stability, and mechanical properties and can be applied directly in extreme environments such as high temperatures and humidity.

The Roles of Exosomes upon Metallic Ions Stimulation in Bone Regeneration.

Metallic ions have been widely investigated and incorporated into bone substitutes for bone regeneration owing to their superior capacity to induce angiogenesis and osteogenesis. Exosomes are key paracrine mediators that play a crucial role in cell-to-cell communication. However, the role of exosomes in metallic ion-induced bone formation and their underlying mechanisms remain unclear. Thus, this review systematically analyzes the effects of metallic ions and metallic ion-incorporated biomaterials on exosome secretion from mesenchymal stem cells (MSCs) and macrophages, as well as the effects of secreted exosomes on inflammation, angiogenesis, and osteogenesis. In addition, possible signaling pathways involved in metallic ion-mediated exosomes, followed by bone regeneration, are discussed. Despite limited investigation, metallic ions have been confirmed to regulate exosome production and function, affecting immune response, angiogenesis, and osteogenesis. Although the underlying mechanism is not yet clear, these insights enrich our understanding of the mechanisms of the metallic ion-induced microenvironment for bone regeneration, benefiting the design of metallic ion-incorporated implants.

Implications of a Carbon Tax Mechanism in Remanufacturing Outsourcing on Carbon Neutrality.

Many governments have imposed methods such as a carbon tax that aim to even out the negative effects of carbon emissions. The taxes levied on different agents lead to different make-buy decisions for production structures and different environmental outcomes. Some original equipment manufacturers (OEMs) outsource remanufacturing to independent remanufacturers (IRs). Thus, a question arises: What are the implications of carbon taxes levied on different agents on remanufacturing outsourcing decisions? To answer this question, we developed two models: (1) acting as common brand owners, OEMs can be taxed for both new and remanufactured products, or (2) acting as different emitters for production and remanufacturing, OEMs are taxed for new products; however, all carbon taxes related to remanufacturing are levied on IRs. Our analysis reveals that, regarding economic performance, firms should undertake a carbon emission tax on their own initiative because this allows the taxpayer to choose more units for its preferred products and leaves its rivals at a huge disadvantage. Moreover, regarding environmental sustainability, carbon emission taxes indeed lead to mitigating the effects of carbon emissions per unit; however, environmental agencies should also pay attention to reducing the total carbon emissions by limiting the volume effects.

LYG-202 inhibits activation of endothelial cells and angiogenesis through CXCL12/CXCR7 pathway in breast cancer.

Angiogenesis is critical for the growth and metastasis of triple-negative breast cancer (TNBC) and its inhibition reduces the risk of progression of metastatic TNBC. In this study, we investigated that LYG-202, a flavonoid with a piperazine substitution, inhibited angiogenesis induced by conditioned media (CM) from MDA-MB-231 cells under hypoxia and revealed its underlying mechanism. The results showed that LYG-202 decreased CXCL12 secretion and CXCR7 expression, leading to suppression of its downstream ERK/AKT/nuclear factor kappa B (NF-κB) signaling, which eventually decreased the expression of MMP-2, MMP-9, RhoA and increased VE-cadherin expression in EA.hy 926 cells treated with CM from MDA-MB-231 cells under hypoxia. The decreased migration ability, increased cell adhesion and inhibited CXCR7 pathway by LYG-202 could also be reproduced in human umbilical vein endothelial cells. More importantly, LYG-202 also inhibited tumor angiogenesis and tumor growth of human breast cancer MDA-MB-231 cells in nude mice through CXCL12/CXCR7 pathway. In summary, LYG-202 is a potential agent to prohibit tumor angiogenesis through inhibiting the activation of endothelial cells.

Adenovirus-mediated GDF-5 promotes the extracellular matrix expression in degenerative nucleus pulposus cells.

OBJECTIVE: To construct a recombinant adenovirus vector-carrying human growth and differentiation factor-5 (GDF-5) gene, investigate the biological effects of adenovirus-mediated GDF-5 (Ad-GDF-5) on extracellular matrix (ECM) expression in human degenerative disc nucleus pulposus (NP) cells, and explore a candidate gene therapy method for intervertebral disc degeneration (IDD). METHODS: Human NP cells of a degenerative disc were isolated, cultured, and infected with Ad-GDF-5 using the AdEasy-1 adenovirus vector system. On Days 3, 7, 14, and 21, the contents of the sulfated glycosaminoglycan (sGAG), deoxyribonucleic acid (DNA) and hydroxyproline (Hyp), synthesis of proteoglycan and collagen II, gene expression of collagen II and aggrecan, and NP cell proliferation were assessed. RESULTS: The adenovirus was an effective vehicle for gene delivery with prolonged expression of GDF-5. Biochemical analysis revealed increased sGAG and Hyp contents in human NP cells infected by Ad-GDF-5 whereas there was no conspicuous change in basal medium (BM) or Ad-green fluorescent protein (GFP) groups. Only cells in the Ad-GDF-5 group promoted the production of ECM, as demonstrated by the secretion of proteoglycan and up-regulation of collagen II and aggrecan at both protein and mRNA levels. The NP cell proliferation was significantly promoted. CONCLUSIONS: The data suggest that Ad-GDF-5 gene therapy is a potential treatment for IDD, which restores the functions of degenerative intervertebral disc through enhancing the ECM production of human NP cells.

Wogonoside inhibits angiogenesis in breast cancer via suppressing Wnt/ß-catenin pathway.

Wogonoside, a main flavonoid component derived from the root of Scutellaria baicalensis Georgi, has been reported to have anti-angiogenesis and anti-leukemia activities. However, whether it can inhibit tumor angiogenesis is unclear. In this study, we investigate the inhibitory effect of wogonoside on angiogenesis in breast cancer and its underlying mechanisms. ELISA assay shows that wogonoside (25, 50, and 100 µM) decreases the secretion of VEGF in MCF-7 cells by 30.0%, 35.4%, and 40.1%, respectively. We find it inhibits angiogenesis induced by the conditioned media from MCF-7 cells in vitro and in vivo by migration, tube formation, rat aortic ring, and chicken chorioallantoic membrane (CAM) assay. Meanwhile, wogonoside can inhibit the growth and angiogenesis of MCF-7 cells xenografts in nude mice. The reduction of tumor weight can be found both in wogonoside (80 mg/kg) and bevacizumab (20 mg/kg) treated group, and the tumor inhibition rate is 42.1% and 48.7%, respectively. In addition, mechanistic studies demonstrate that wogonoside suppresses the activation of Wnt/ß-catenin pathway in MCF-7 cells. Wogonoside (100 µM) decreases the intracellular level of Wnt3a, increases the expression of GSK-3ß, AXIN, and promotes the phosphorylation of ß-catenin for proteasome degradation significantly. Furthermore, the nuclear accumulation of ß-catenin and the DNA-binding activity of ß-catenin/TCF/Lef complex are inhibited by 49.2% and 28.7%, respectively, when treated with 100 µM wogonoside. Taken together, our findings demonstrate that wogonoside is a potential inhibitor of tumor angiogenesis and can be developed as a therapeutic agent for breast cancer. © 2015 Wiley Periodicals, Inc.

Repair of articular cartilage defects in rabbits through tissue-engineered cartilage constructed with chitosan hydrogel and chondrocytes.

OBJECTIVE: In our previous work, we prepared a type of chitosan hydrogel with excellent biocompatibility. In this study, tissue-engineered cartilage constructed with this chitosan hydrogel and costal chondrocytes was used to repair the articular cartilage defects. METHODS: Chitosan hydrogels were prepared with a crosslinker formed by combining 1,6-diisocyanatohexane and polyethylene glycol. Chitosan hydrogel scaffold was seeded with rabbit chondrocytes that had been cultured for one week in vitro to form the preliminary tissue-engineered cartilage. This preliminary tissue-engineered cartilage was then transplanted into the defective rabbit articular cartilage. There were three treatment groups: the experimental group received preliminary tissue-engineered cartilage; the blank group received pure chitosan hydrogels; and, the control group had received no implantation. The knee joints were harvested at predetermined time. The repaired cartilage was analyzed through gross morphology, histologically and immunohistochemically. The repairs were scored according to the international cartilage repair society (ICRS) standard. RESULTS: The gross morphology results suggested that the defects were repaired completely in the experimental group after twelve weeks. The regenerated tissue connected closely with subchondral bone and the boundary with normal tissue was fuzzy. The cartilage lacuna in the regenerated tissue was similar to normal cartilage lacuna. The results of ICRS gross and histological grading showed that there were significant differences among the three groups (P<0.05). CONCLUSIONS: Chondrocytes implanted in the scaffold can adhere, proliferate, and secrete extracellular matrix. The novel tissue-engineered cartilage constructed in our research can completely repair the structure of damaged articular cartilage.

Wogonin inhibits LPS-induced vascular permeability via suppressing MLCK/MLC pathway.

Wogonin, a naturally occurring monoflavonoid extracted from the root of Scutellaria baicalensis Georgi, has been shown to have anti-inflammatory and anti-tumor activities and inhibits oxidant stress-induced vascular permeability. However, the influence of wogonin on vascular hyperpermeability induced by overabounded inflammatory factors often appears in inflammatory diseases and tumor is not well known. In this study, we evaluate the effects of wogonin on LPS induced vascular permeability in human umbilical vein endothelial cells (HUVECs) and investigate the underlying mechanisms. We find that wogonin suppresses the LPS-stimulated hyperactivity and cytoskeleton remodeling of HUVECs, promotes the expression of junctional proteins including VE-Cadherin, Claudin-5 and ZO-1, as well as inhibits the invasion of MDA-MB-231 across EC monolayer. Miles vascular permeability assay proves that wogonin can restrain the extravasated Evans in vivo. The mechanism studies reveal that the expressions of TLR4, p-PLC, p-MLCK and p-MLC are decreased by wogonin without changing the total steady state protein levels of PLC, MLCK and MLC. Moreover, wogonin can also inhibit KCl-activated MLCK/MLC pathway, and further affect vascular permeability. Significantly, compared with wortmannin, the inhibitor of MLCK/MLC pathway, wogonin exhibits similar inhibition effects on the expression of p-MLCK, p-MLC and LPS-induced vascular hyperpermeability. Taken together, wogonin can inhibit LPS-induced vascular permeability by suppressing the MLCK/MLC pathway, suggesting a therapeutic potential for the diseases associated with the development of both inflammatory and tumor.