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Some traditional Chinese medicine (TCM) has been applied in bone repair, however, hydroxy-safflower yellow A (HYSA), one composition of safflower of the typical invigorating the circulation of TCM, has little been studied in orthopedics field for osteogenesis and angiogenesis clinically. Herein, we hypothetically speculated that the synthetic bioactive glasses (BG, 1393) scaffolds carried HYSA by a 3D print technique could enhance osteogenic repair properties. Notably, scaffolds coating chitosan/sodium alginate endowed with excellent drug control release ability, and significantly improved the BG mechanical strength. HYSA was loaded into BG scaffolds by coating chitosan/sodium alginate film, and the osteogenesis and angiogenesis of the HYSA/scaffolds were evaluated in vitro and in vivo. In vitro the cell culture results exhibited that the high dose of HYSA (0.5 mg/ml) loaded scaffolds can promote the proliferation of bone marrow stromal cells (rBMSCs) and migration, tubule formation of human umbilical vein endothelial cells (HUVECs). The active alkaline phosphatase (ALP) of rBMSCs can also be improved by the high dose of HYSA/scaffolds. Results of qRT-PCR and Western blot indicated that the high dose of HYSA/scaffolds can up-regulate ALP, OCN, OPN and RUNX-2 expression and relative protein secretion of the HIF-1α and BMP-2. In the animal experiment, the high dose of HYSA/scaffolds has a significantly better capacity to promote new bone formation than the undoped scaffolds at 8 weeks post-surgery. Thus, our results claimed that the novel HYSA/scaffolds hold the substantial potential to be further developed as effective and safe bone tissue engineering biomaterials for bone regeneration by combining enhanced osteogenesis and angiogenesis., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The high surface area ratio and special structure of mesoporous bioactive glass (MBG) endow it with excellent physical adsorption of various drugs without destroying the chemical activity. Silicate 1393 bioactive glass (1393) is famous for its fantastic biodegradability and osteogenesis. Herein, we have built a novel vehicle-like drug delivery 3D printing scaffold with multiplexed drug delivery capacity by coating MBG on the surface of 1393 (1393@MBG). Furthermore, we have applied DEX and BMP-2 on the 1393@MBG scaffold to endow it with antibacterial and osteogenic properties. Results indicated that this 1393@MBG scaffold could effectively load and controlled release BMP-2, DNA and DEX, which can be applied for orthopedic treatment. The in vitro study showed that the DEX loaded 1393@MBG exhibited excellent antibacterial ability, which was evaluated by Staphylococcus aureus ( S. aureus ), and the BMP-2 loaded 1393@MBG can improve the alkaline phosphatase (ALP) activity and upregulate the expression of osteogenesis-related genes (OCN and RUNX2) of human bone mesenchymal stem cells (hBMSCs). Moreover, the in vivo study further confirmed that the BMP-2 loaded 1393@MBG group showed better osteogenic capacity as compared to that of the 1393 group in a rat femoral defect. Together, these results suggested that the vehicle-like drug delivery 3D printing scaffold 1393@MBG could be a promising candidate for bone repair and relative bone disease treatment., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The composite scaffolds of bioactive glasses and polymers are often used in bone regeneration which could improve the stiffness, compressive strength and bioactivity of polymers while maintaining the osteoconductivity and osteoinductivity of bioactive glasses. But due to complicated situations and limitations of compositing process, the prepared composite materials have low uniformity and obvious phase separation, leading to problems such as poor mechanical properties and inferior new bone formation capacity. In this paper, a modified sol-gel processing technique was used to realize the homogeneous inorganic-organic composites. After hydrolysis of the metal alkoxide, the sol was mixed with the aqueous solution of polyvinyl alcohol (PVA), and through gelation and chemical reaction, the mixture was solidified into the inorganic-organic composite hydrogel. The composites showed as a uniform single phase with interpenetrating networks of PVA gel and borosilicate gel (BG) that chemically and physically interacted at the scale of molecular or nanometer, therefore PVA-BG hybrids were obtained. When immersed in phosphate-buffered saline, the PVA-BG hybrid-derived scaffolds released beneficial ions into the medium and converted to hydroxyapatite. The scaffolds were not toxic to the rat bone marrow-derived mesenchymal stem cells (rBMSCs), and supported rBMSCs proliferation. Furthermore, the alkaline phosphatase activity of the rBMSCs and the expression levels of osteogenic-related genes (alkaline phosphatase, osteocalcin and runt-related transcription factor 2) increased significantly with increasing amount of BG in the hybrid scaffolds. Finally, the bone defect repair results of critical-sized femoral condyle defect rat model demonstrated that PVA-BG hybrid scaffolds could enhance bone regeneration compared with PVA scaffolds. The results suggested that PVA-BG hybrid scaffolds may be a promising biomaterial for bone regeneration., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The osteogenic capacity of synthetic bone substitutes is will be highly stimulated by a well-established functional vascularized network. Cobalt (Co) ions are known that can generate a hypoxia-like response and stimulates the production of kinds of angiogenic factors. Herein, we investigated the mechanism of cobalt-doped bioactive borosilicate (36B 2 O 3 , 22CaO, 18SiO 2 , 8MgO, 8K 2 O, 6Na 2 O, 2P 2 O 5 ; mol%) glass scaffolds for bone tissues repairing and blood vessel formation in the critical-sized cranial defect site of rats and their effects on the hBMSCs in vitro were researched. The scaffolds can control release Co 2+ ions and convert into hydroxyapatite soaking in simulative body fluids (SBF). The fabircated scaffolds without cytotoxic strongly improves HIF-1α generation, VEGF protein secretion, ALP activity and upregulates the expression of osteoblast and angiogenic relative genes in hBMSCs. Eight weeks after implantation, the bioactive glass scaffolds with 3wt % CoO remarkablely enhance bone regeneration and blood vascularized network at the defective site. In conclusion, as a graft material for bone defects, low-oxygen simulated cobalt-doped bioactive glass scaffold is promising., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Background: In the field of tissue engineering, there is currently increasing interest in new biomedical materials with high osteogenic ability and comparable mechanical function to repair bone defects. Three-dimensional (3-D) bioactive borosilicate glass (BG) scaffolds exhibit uniform interconnected macro-pores, high porosity and high compressive strength. In this study, we fabricated 3-D BG scaffolds by the 3D printing technique, then coated the surface of the 3-D BG scaffolds with mesoporous bioactive glass (MBG) (BG-MBG scaffold). Methods: The biocompatibility of the BG-MBG scaffolds was evaluated by assessing biodegradability, cell proliferation, alkaline phosphatase (ALP) activity and by quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis of osteogenic gene expression with human bone marrow stromal cells (hBMSCs). Moreover, the BG-MBG scaffolds were used to repair rat femoral defects and their performance was evaluated using microcomputed tomography (micro-CT), fluorescence labeling, histological analysis and immunohistochemical (IHC) analysis. Results: The results showed that the BG-MBG scaffolds possessed ordered nearly 4nm meso-pores and regular macro-pores, as well as good biodegradability, and that they stimulated the proliferation and osteogenic differentiation of hBMSCs. In in vivo studies, the result of micro-CT reconstructed images (BG-9M group, 0.63 ± 0.02 g/cm 3 and BG group 0.13 ± 0.02 g/cm 3 ) and van Gieson staining (BG-9M groups, 62.67 ± 3.39% and BG group, 12.33 ± 2.58%) showed that the BG-MBG scaffolds could significantly enhance new bone formation in both inner and peripheral scaffolds in defects, in and in without the presence of growth factors or stem cells ( P < 0.05). Conclusions: It is believed from these results that the BG-MBG scaffolds possess excellent osteoinductive and osteogenic properties which will make them appealing candidates for bone defect repair. The novelty of our research is to provide a new material to treat bone defects in clinic., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

The biomaterials with high osteogenic ability are being intensively investigated. In this study, we evaluated the bioactivity and osteogenesis of BG-Zn scaffolds in vitro and in vivo with a rodent calvarial defects model. Zinc containing borosilicate bioactive glass was prepared by doping glass with 1.5, 5 and 10 wt.% ZnO (denoted as BG-1.5Zn, BG-5Zn and BG-10Zn, respectively). When immersed in simulated body fluid, dopant ZnO retarded the degradation process, but did not affect the formation of hydroxyapatite (HA) after long-period soaking. BG-Zn scaffolds showed controlled release of Zn ions into the medium for over 8 weeks. Human bone marrow derived stem cells (hBMSCs) attached well on the BG-1.5Zn and BG-5Zn scaffolds, which exhibited no cytotoxicity to hBMSCs. In addition, the alkaline phosphatase activity of the hBMSCs increased with increasing dopant amount in the glass, while the BG-10Zn group showed over-dose of Zn. Furthermore, when implanted in rat calvarial defects for 8 weeks, the BG-5Zn scaffolds showed a significantly better capacity to regenerate bone tissue compared to the non-doping scaffolds. Generally, these results showed the BG-Zn scaffolds with high osteogenic capacity will be promising candidates using in bone tissue repair and regeneration., (Copyright © 2015. Published by Elsevier B.V.)

There is growing interest in the use of synthetic biomaterials to deliver inorganic ions that are known to stimulate angiogenesis and osteogenesis in vivo. In the present study, we investigated the effects of varying amounts of copper in a bioactive glass on the response of human bone marrow-derived mesenchymal stem cells (hBMSCs) in vitro and on blood vessel formation and bone regeneration in rat calvarial defects in vivo. Porous scaffolds of a borosilicate bioactive glass (composition 6Na2O, 8K2O, 8MgO, 22CaO, 36B2O3, 18SiO2, 2P2O5, mol.%) doped with 0.5, 1.0 and 3.0wt.% CuO were created using a foam replication method. When immersed in simulated body fluid, the scaffolds released Cu ions into the medium and converted to hydroxyapatite. At the concentrations used, the Cu in the glass was not toxic to the hBMSCs cultured on the scaffolds in vitro. The alkaline phosphatase activity of the hBMSCs and the expression levels of angiogenic-related genes (vascular endothelial growth factor and basic fibroblast growth factor) and osteogenic-related genes (runt-related transcription factor 2, bone morphogenetic protein-2 and osteopontin) increased significantly with increasing amount of Cu in the glass. When implanted in rat calvarial defects in vivo, the scaffolds (3wt.% CuO) significantly enhanced both blood vessel formation and bone regeneration in the defects at 8weeks post-implantation. These results show that doping bioactive glass implants with Cu is a promising approach for enhancing angiogenesis and osteogenesis in the healing of osseous defects., (Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Bioactive borosilicate glass scaffolds with the pores of several hundred micrometers and a competent compressive strength were prepared through replication method. The in vitro degradation and bioactivity behaviors of the scaffolds have been investigated by immersing the scaffolds statically in diluted phosphate solution at 37 degrees C, up to 360 h. To monitor the degradation progress of the scaffolds, the amount of leaching elements from the scaffolds were determined by ICP-AES. The XRD and SEM results reveal that, during the degradation of scaffolds, the borosilicate scaffolds converted to hydroxyapatite. The compressive strength of the scaffolds decreased during degradation, in the way that can be well predicted by the degradation products, or the leachates, from the scaffolds. MTT assay results demonstrate that the degradation products have little, if any, inhibition effect on the cell proliferation, when diluted to a certain concentration ([B] <2.690 and pH value at neutral level). The study shows that borosilicate glass scaffold could be a promising candidate for bone tissue engineering material.

Three-dimensional macroporous scaffolds with the pore size of 200-500 mum were fabricated by replication method using bioactive borosilicate glass from Na(2)O-K(2)O-MgO-CaO-SiO(2)-P(2)O(5)-B(2)O(3) system. The effects of the strength of the strut in reticulated scaffold, as well as the geometrical parameter of the scaffold on the strength of reticulated scaffold were investigated. Scanning electron microscope (SEM) and X-ray diffraction (XRD) results show that the solidified glass struts in the reticulated scaffold could be obtained through a sufficient vicious flow of glass, during the fabrication. By increasing the solid content in slurries, from which the scaffold was made, the load-bearing units of the reticulated scaffold switch from struts to the walls between the pores, and the compressive strength dramatically climbs higher than the theoretical strength calculated by Gibson model. In particular, the compressive strength of the reticulated scaffold, as high as approximately 10 MPa with the porosity of approximately 70%, is close to the reported compressive values of human cancellous bone. This indicates the bioactive borosilicate glass-based scaffold is a promising candidate for bone tissue engineering.

The development of synthetic scaffolds with a desirable combination of properties, such as bioactivity, the ability to locally deliver antibacterial agents and high osteogenic capacity, is a challenging but promising approach in bone tissue engineering. In this study, scaffolds of a borosilicate bioactive glass (composition: 6Na2O, 8K2O, 8MgO, 22CaO, 36B2O3, 18SiO2, 2P2O5; mol%) with controllable antibacterial activity were developed by doping the parent glass with varying amounts of Ag2O (0.05, 0.5, and 1.0 wt%). The addition of the Ag2O lowered the compressive strength and degradation of the bioactive glass scaffolds but it did not affect the formation of hydroxyapatite on the surface of the glass as determined by energy dispersive x-ray analysis, x-ray diffraction, and Fourier transform infrared analysis. The Ag2O-doped scaffolds showed a sustained release of Ag ions over more than 8 weeks in simulated body fluid and resistance against colonization by the bacterial strains Escherichia coli and Staphylococcus aureus. In vitro cell culture showed better adhesion, proliferation, and alkaline phosphatase activity of murine osteoblastic MC3T3-E1 cells on the Ag2O-doped bioactive glass scaffolds than on the undoped scaffolds. The results indicate that these Ag-doped borosilicate bioactive glass scaffolds may have potential in repairing bone coupled with providing a lower risk of bacterial infection. [ABSTRACT FROM AUTHOR]

Copper doped borosilicate glasses (BG–Cu) were studied by means of FT-IR, Raman, UV–vis and NMR spectroscopies to investigate the changes that appeared in the structure of borosilicate glass matrix by doping copper ions. Micro-fil and immunohistochemistry analysis were applied to study the angiogenesis of its derived scaffolds in vivo. Results indicated that the Cu ions significantly increased the B–O bond of BO 4 groups at 980 cm −1 , while they decrease that of BO 2 O − groups at 1440–1470 cm −1 as shown by Raman spectra. A negative shift was observed from 11 B and 29 Si NMR spectra. The 11 B NMR spectra exhibited a clear transformation from BO 3 into BO 4 groups, caused by the agglutination effect of the Cu ions and the charge balance of the agglomerate in the glass network, leading to a more stable glass network and lower ions release rate in the degradation process. Furthermore, the BG–Cu scaffolds significantly enhanced blood vessel formation in rat calvarial defects at 8 weeks post-implantation. Generally, it suggested that the introduction of Cu into borosilicate glass endowed glass and its derived scaffolds with good properties, and the cooperation of Cu with bioactive glass may pave a new way for tissue engineering. [ABSTRACT FROM AUTHOR]

• "Integrative treatment" anti-tumor/bone repair BGM scaffolds were fabricated. • BGM can retain MoS 2 for >60 days implying its' photothermal ability. • BGM can reduce MNNG/HOS viability and inhibit tumor growth in vitro and in vivo. • BGM stimulate differentiation of rBMSCs, upregulate osteogenetic genes expression. • The BGM scaffolds can promote bone tissues repairing in rat calvarial defects. Malignant bone tumors have caused great obstacles and serious illnesses for tumor recurrence and difficulty in reconstructing and repairing large defects after tumorectomy. Additionally, long-term efficacy, satisfactory biocompatibility and excellent properties for anti-tumor agents are necessary in the biomedical field. To solve these problems, a novel idea has been proposed on building an integrative anti-tumor/bone repairing scaffold by covering photothermal therapy (PTT) composite MoS 2 -PLGA film on the surface of borosilicate bioactive glass (BG). In our study, the MoS 2 -integrated composite BG (BGM) scaffolds can rapidly and effectively elevate temperature, and they exhibited excellent photothermal stability, under 808 nm laser irradiation. Notably, the BGM scaffolds can effectively reduce the viability of osteosarcoma cells (MNNG/HOS) in vitro as well as inhibit the tumor growth in nude mice. Furthermore, the prepared BGM scaffolds can stimulate the proliferation and differentiation of rat bone mesenchymal stem cells (rBMSCs), upregulate the expression of osteogenesis-related genes (Runx-2, OCN and Col-I) in vitro and promote in vivo bone repair in critical-sized rat calvarial defects. Therefore, the novel MoS 2 -integrated composite BG scaffolds are highly promising for the treatment of tumor-related bone defects, offering ideas for the manufacture of new materials in the tissue engineering field. [ABSTRACT FROM AUTHOR]