Corrigendum to "Strontium modulates osteogenic activity of bone cement composed of bioactive borosilicate glass particles by activating Wnt/ß-catenin signaling pathway" [Bioact. Mater. 5 (2020) 334-347].

[This corrects the article DOI: 10.1016/j.bioactmat.2020.02.016.].

Strontium modulates osteogenic activity of bone cement composed of bioactive borosilicate glass particles by activating Wnt/ß-catenin signaling pathway.

There is a need for synthetic grafts to reconstruct large bone defects using minimal invasive surgery. Our previous study showed that incorporation of Sr into bioactive borate glass cement enhanced the osteogenic capacity in vivo. However, the amount of Sr in the cement to provide an optimal combination of physicochemical properties and capacity to stimulate bone regeneration and the underlying molecular mechanism of this stimulation is yet to be determined. In this study, bone cements composed of bioactive borosilicate glass particles substituted with varying amounts of Sr (0 mol% to 12 mol% SrO) were created and evaluated in vitro and in vivo. The setting time of the cement increased with Sr substitution of the glass. Upon immersion in PBS, the cement degraded and converted more slowly to HA (hydroxyapatite) with increasing Sr substitution. The released Sr2+ modulated the proliferation, differentiation, and mineralization of hBMSCs (human bone marrow mesenchymal stem cells) in vitro. Osteogenic characteristics were optimally enhanced with cement (designated BG6Sr) composed of particles substituted with 6mol% SrO. When implanted in rabbit femoral condyle defects, BG6Sr cement supported better peri-implant bone formation and bone-implant contact, comparing to cements substituted with 0mol% or 9mol% SrO. The underlying mechanism is involved in the activation of Wnt/ß-catenin signaling pathway in osteogenic differentiation of hBMSCs. These results indicate that BG6Sr cement has a promising combination of physicochemical properties and biological performance for minimally invasive healing of bone defects.

Mechanical and degradation properties of poly(methyl methacrylate) cement/borate bioactive glass composites.

Bone cement is used extensively in orthopedics to anchor prostheses to bone and fill voids. Incorporating bioactive glass into poly(methyl methacrylate) (PMMA)-based bone cement could potentially improve its effectiveness for these tasks. This study characterizes the mechanical and degradation properties of composites containing PMMA-based bone cement and particles of borate bioactive glass designated as 13-93B3. Glass particles of size 5, 33, and 100 µm were mixed with PMMA bone cement to create composites containing 20, 30, and 40 wt % glass. Composites and a bone cement control were soaked in phosphate-buffered saline. Compressive strength, Young's modulus, weight loss, water uptake, solution pH, and ionic concentrations were measured over 21 days. The compressive strengths of composites decreased over 21 days. Average Young's moduli of the composites remained below 3 GPa. Weight loss and water uptake of specimens did not exceed 2 and 6%, respectively. Boron concentrations and pH of all solutions increased over time, with higher glass weight fractions leading to higher pH values. Results demonstrated that the composite can sustain glass degradation and ionic release without compromising short-term mechanical strength.

Relaxin enhances bone regeneration with BMP-2-loaded hydroxyapatite microspheres.

Our aims were to 1) evaluate the capacity of hollow hydroxyapatite (HA) microspheres (212-250 µm) to serve as a delivery system for controlled release of BMP-2 in vitro and 2) examine relaxin as an enhancer of BMP-2 for bone regeneration. Hollow HA microspheres were converted from borate glass microspheres and characterized using X-ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscopy, and the Brunauer-Emmett-Teller method. The microspheres loaded with BMP-2 and relaxin were implanted for 6 weeks in Sprague Dawley rats with calvarial defects. BMP-2 alone in the range up to 1 µg per defect exhibited dose-dependent bone regeneration while relaxin alone in the range up to 0.25 µg per defect did not promote bone regeneration. When compared with BMP-2 alone (1 µg per defect), a 50% reduction in the BMP-2 dose was achieved with the addition of 0.05, 0.1, or 0.25 µg of relaxin per defect. These results show that loading HA microspheres with a combination of relaxin and BMP-2 can significantly reduce the BMP-2 dose required to regenerate an equivalent amount of bone.

Characterization of the conversion of bone cement and borate bioactive glass composites.

Borate bioactive glass 13-93B3 converts into an osteoconductive hydroxyapatite-like material in a liquid medium. In this study, 13-93B3 was incorporated into a commercial PMMA (poly(methyl methacrylate)) bone cement, and the conversion of the glass into a precipitate in solution was investigated with scanning electron microscopy, energy dispersive X-ray spectroscopy, Fourier transform infrared (spectroscopy)-attenuated total reflection, and micro-Raman spectroscopy. Glass particles of 5, 33, and 100 µm diameter were each mixed with the PMMA cement to create 20, 30, and 40% glass-loaded composites. Precipitate formation was found to be a calcium-deficient apatite partially substituted with magnesium ions that resembles native bone material and would ideally encourage bone growth better than stoichiometric hydroxyapatite. Composites of bone cement and 13-93B3 show promise as a means of encouraging bone attachment to the surface of the bone cement.

Antibiotic Elution and Mechanical Strength of PMMA Bone Cement Loaded With Borate Bioactive Glass.

Introduction: Local delivery of antibiotics using bone cement as the delivery vehicle is an established method of managing implant-associated orthopedic infections. Various fillers have been added to cement to increase antibiotic elution, but they often do so at the expense of strength. This study evaluated the effect of adding a borate bioactive glass, previously shown to promote bone formation, on vancomycin elution from PMMA bone cement. Methods: Five cement composites were made: three loaded with borate bioactive glass along with 0, 1, and 5 grams of vancomycin and two without any glass but with 1 and 5 grams vancomycin to serve as controls. The specimens were soaked in PBS. Eluate of vancomycin was collected every 24 hours and analyzed by HPLC. Orthopedic-relevant mechanical properties of each composite were tested over time. Results: The addition of borate bioactive glass provided an increase in vancomycin release at Day 1 and an increase in sustained vancomycin release throughout the treatment period. An 87.6% and 21.1% increase in cumulative vancomycin release was seen for both 1g and 5g loading groups, respectively. Compressive strength of all composites remained above the weight-bearing threshold of 70 MPa throughout the duration of the study with the glass-containing composites showing comparable strength to their respective controls. Conclusion: The incorporation of borate bioactive glass into commercial PMMA bone cement can significantly increase the elution of vancomycin. The mechanical strength of the cement-glass composites remained above 70 MPa even after soaking for 8 weeks, suggesting their suitability for orthopedic weight-bearing applications.

Tough and strong porous bioactive glass-PLA composites for structural bone repair.

Bioactive glass scaffolds have been used to heal small contained bone defects but their application to repairing structural bone is limited by concerns about their mechanical reliability. In the present study, the addition of an adherent polymer layer to the external surface of strong porous bioactive glass (13-93) scaffolds was investigated to improve their toughness. Finite element modeling (FEM) of the flexural mechanical response of beams composed of a porous glass and an adherent polymer layer predicted a reduction in the tensile stress in the glass with increasing thickness and elastic modulus of the polymer layer. Mechanical testing of composites with structures similar to the models, formed from 13-93 glass and polylactic acid (PLA), showed trends predicted by the FEM simulations but the observed effects were considerably more dramatic. A PLA layer of thickness -400 µm, equal to -12.5% of the scaffold thickness, increased the load-bearing capacity of the scaffold in four-point bending by ~50%. The work of fracture increased by more than 10,000%, resulting in a non-brittle mechanical response. These bioactive glass-PLA composites, combining bioactivity, high strength, high work of fracture and an internal architecture shown to be conducive to bone infiltration, could provide optimal implants for healing structural bone defects.

Enhanced osteointegration of poly(methylmethacrylate) bone cements by incorporating strontium-containing borate bioactive glass.

Although poly(methylmethacrylate) (PMMA) cements are widely used in orthopaedics, they have numerous drawbacks. This study aimed to improve their bioactivity and osseointegration by incorporating strontium-containing borate bioactive glass (SrBG) as the reinforcement phase and bioactive filler of PMMA cement. The prepared SrBG/PMMA composite cements showed significantly decreased polymerization temperature when compared with PMMA and retained properties of appropriate setting time and high mechanical strength. The bioactivity of SrBG/PMMA composite cements was confirmed in vitro, evidenced by ion release (Ca, P, B and Sr) from SrBG particles. The cellular responses of MC3T3-E1 cells in vitro demonstrated that SrBG incorporation could promote adhesion, migration, proliferation and collagen secretion of cells. Furthermore, our in vivo investigation revealed that SrBG/PMMA composite cements presented better osseointegration than PMMA bone cement. SrBG in the composite cement could stimulate new-bone formation around the interface between the composite cement and host bone at eight and 12 weeks post-implantation, whereas PMMA bone cement only stimulated development of an intervening connective tissue layer. Consequently, the SrBG/PMMA composite cement may be a better alternative to PMMA cement in clinical applications and has promising orthopaedic applications by minimal invasive surgery.

Evaluation of an injectable bioactive borate glass cement to heal bone defects in a rabbit femoral condyle model.

There is a need for synthetic biomaterials to heal bone defects using minimal invasive surgery. In the present study, an injectable cement composed of bioactive borate glass particles and a chitosan bonding solution was developed and evaluated for its capacity to heal bone defects in a rabbit femoral condyle model. The injectability and setting time of the cement in vitro decreased but the compressive strength increased (8±2MPa to 31±2MPa) as the ratio of glass particles to chitosan solution increased (from 1.0gml-1 to 2.5gml-1). Upon immersing the cement in phosphate-buffered saline, the glass particles reacted and converted to hydroxyapatite, imparting bioactivity to the cement. Osteoblastic MC3T3-E1 cells showed enhanced proliferation and alkaline phosphatase activity when incubated in media containing the soluble ionic product of the cement. The bioactive glass cement showed a better capacity to stimulate bone formation in rabbit femoral condyle defects at 12weeks postimplantation when compared to a commercial calcium sulfate cement. The injectable bioactive borate glass cement developed in this study could provide a promising biomaterial to heal bone defects by minimal invasive surgery.

Creation of bioactive glass (13-93) scaffolds for structural bone repair using a combined finite element modeling and rapid prototyping approach.

There is a clinical need for synthetic bioactive materials that can reliably repair intercalary skeletal tissue loss in load-bearing bones. Bioactive glasses have been investigated as one such material but their mechanical response has been a concern. Previously, we created bioactive silicate glass (13-93) scaffolds with a uniform grid-like microstructure which showed a compressive strength comparable to human cortical bone but a much lower flexural strength. In the present study, finite element modeling (FEM) was used to re-design the scaffold microstructure to improve its flexural strength without significantly lowering its compressive strength and ability to support bone infiltration in vivo. Then scaffolds with the requisite microstructures were created by a robotic deposition method and tested in four-point bending and compression to validate the FEM simulations. In general, the data validated the predictions of the FEM simulations. Scaffolds with a porosity gradient, composed of a less porous outer region and a more porous inner region, showed a flexural strength (34±5MPa) that was more than twice the value for the uniform grid-like microstructure (15±5MPa) and a higher compressive strength (88±20MPa) than the grid-like microstructure (72±10MPa). Upon implantation of the scaffolds for 12weeks in rat calvarial defects in vivo, the amount of new bone that infiltrated the pore space of the scaffolds with the porosity gradient (37±16%) was similar to that for the grid-like scaffolds (35±6%). These scaffolds with a porosity gradient that better mimics the microstructure of human long bone could provide more reliable implants for structural bone repair.

Effect of copper-doped silicate 13-93 bioactive glass scaffolds on the response of MC3T3-E1 cells in vitro and on bone regeneration and angiogenesis in rat calvarial defects in vivo.

The release of inorganic ions from biomaterials could provide an alternative approach to the use of growth factors for improving tissue healing. In the present study, the release of copper (Cu) ions from bioactive silicate (13-93) glass scaffolds on the response of cells in vitro and on bone regeneration and angiogenesis in vivo was studied. Scaffolds doped with varying concentrations of Cu (0-2.0wt.% CuO) were created with a grid-like microstructure by robotic deposition. When immersed in simulated body fluid in vitro, the Cu-doped scaffolds released Cu ions into the medium in a dose-dependent manner and converted partially to hydroxyapatite. The proliferation and alkaline phosphatase activity of pre-osteoblastic MC3T3-E1 cells cultured on the scaffolds were not affected by 0.4 and 0.8wt.% CuO in the glass but they were significantly reduced by 2.0wt.% CuO. The percent new bone that infiltrated the scaffolds implanted for 6weeks in rat calvarial defects (46±8%) was not significantly affected by 0.4 or 0.8wt.% CuO in the glass whereas it was significantly inhibited (0.8±0.7%) in the scaffolds doped with 2.0wt.% CuO. The area of new blood vessels in the fibrous tissue that infiltrated the scaffolds increased with CuO content of the glass and was significantly higher for the scaffolds doped with 2.0wt.% CuO. Loading the scaffolds with bone morphogenetic protein-2 (1µg/defect) significantly enhanced bone infiltration and reduced fibrous tissue in the scaffolds. These results showed that doping the 13-93 glass scaffolds with up to 0.8wt.% CuO did not affect their biocompatibility whereas 2.0wt.% CuO was toxic to cells and detrimental to bone regeneration.

Influence of Cu doping in borosilicate bioactive glass and the properties of its derived scaffolds.

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 BO4 groups at 980 cm(-1), while they decrease that of BO2O(-) 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 BO3 into BO4 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.

Preparation of resorbable carbonate-substituted hollow hydroxyapatite microspheres and their evaluation in osseous defects in vivo.

Hollow hydroxyapatite (HA) microspheres, with a high-surface-area mesoporous shell, can provide a unique bioactive and osteoconductive carrier for proteins to stimulate bone regeneration. However, synthetic HA has a slow resorption rate and a limited ability to remodel into bone. In the present study, hollow HA microspheres with controllable amounts of carbonate substitution (0-12 wt.%) were created using a novel glass conversion route and evaluated in vitro and in vivo. Hollow HA microspheres with ~12 wt.% of carbonate (designated CHA12) showed a higher surface area (236 m(2) g(-1)) than conventional hollow HA microspheres (179 m(2)g(-1)) and a faster degradation rate in a potassium acetate buffer solution. When implanted for 12 weeks in rat calvarial defects, the CHA12 and HA microspheres showed a limited capacity to regenerate bone but the CHA12 microspheres resorbed faster than the HA microspheres. Loading the microspheres with bone morphogenetic protein-2 (BMP2) (1 µg per defect) stimulated bone regeneration and accelerated resorption of the CHA12 microspheres. At 12 weeks, the amount of new bone in the defects implanted with the CHA12 microspheres (73±8%) was significantly higher than the HA microspheres (59±2%) while the amount of residual CHA12 microspheres (7±2% of the total defect area) was significantly lower than the HA microspheres (21±3%). The combination of these carbonate-substituted HA microspheres with clinically safe doses of BMP2 could provide promising implants for healing non-loaded bone defects.

Comparison of Borate Bioactive Glass and Calcium Sulfate as Implants for the Local Delivery of Teicoplanin in the Treatment of Methicillin-Resistant Staphylococcus aureus-Induced Osteomyelitis in a Rabbit Model.

There is growing interest in biomaterials that can cure bone infection and also regenerate bone. In this study, two groups of implants composed of 10% (wt/wt) teicoplanin (TEC)-loaded borate bioactive glass (designated TBG) or calcium sulfate (TCS) were created and evaluated for their ability to release TEC in vitro and to cure methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis in a rabbit model. When immersed in phosphate-buffered saline (PBS), both groups of implants provided a sustained release of TEC at a therapeutic level for up to 3 to 4 weeks while they were gradually degraded and converted to hydroxyapatite. The TBG implants showed a longer duration of TEC release and better retention of strength as a function of immersion time in PBS. Infected rabbit tibiae were treated by debridement, followed by implantation of TBG or TCS pellets or intravenous injection with TEC, or were left untreated. Evaluation at 6 weeks postimplantation showed that the animals implanted with TBG or TCS pellets had significantly lower radiological and histological scores, lower rates of MRSA-positive cultures, and lower bacterial loads than those preoperatively and those of animals treated intravenously. The level of bone regeneration was also higher in the defects treated with the TBG pellets. The results showed that local TEC delivery was more effective than intravenous administration for the treatment of MRSA-induced osteomyelitis. Borate glass has the advantages of better mechanical strength, more desirable kinetics of release of TEC, and a higher osteogenic capacity and thus could be an effective alternative to calcium sulfate for local delivery of TEC.

Surface modulation of silicon nitride ceramics for orthopaedic applications.

Silicon nitride (Si3N4) has a distinctive combination of material properties such as high strength and fracture toughness, inherent phase stability, scratch resistance, low wear, biocompatibility, hydrophilic behavior, excellent radiographic imaging and resistance to bacterial adhesion, all of which make it an attractive choice for orthopaedic implants. Unlike oxide ceramics, the surface chemistry and topography of Si3N4 can be engineered to address potential in vivo needs. Morphologically, it can be manufactured to have an ultra-smooth or highly fibrous surface structure. Its chemistry can be varied from that of a silica-like surface to one which is predominately comprised of silicon-amines. In the present study, a Si3N4 bioceramic was subjected to thermal, chemical, and mechanical treatments in order to induce changes in surface composition and features. The treatments included grinding and polishing, etching in aqueous hydrofluoric acid, and heating in nitrogen or air. The treated surfaces were characterized using a variety of microscopy techniques to assess morphology. Surface chemistry and phase composition were determined using X-ray photoelectron and Raman spectroscopy, respectively. Streaming potential measurements evaluated surface charging, and sessile water drop techniques assessed wetting behavior. These treatments yielded significant differences in surface properties with isoelectric points ranging from 2 to 5.6, and moderate to extremely hydrophilic water contact angles from ∼65° to ∼8°. This work provides a basis for future in vitro and in vivo studies which will examine the effects of these treatments on important orthopaedic properties such as friction, wear, protein adsorption, bacteriostasis and osseointegration. STATEMENT OF SIGNIFICANCE: Silicon nitride (Si3N4) exhibits a unique combination of bulk mechanical and surface chemical properties that make it an ideal biomaterial for orthopaedic implants. It is already being used for interbody spinal fusion cages and is being developed for total joint arthroplasty. Its surface texture and chemistry are both highly tunable, yielding physicochemical combinations that may lead to enhanced osseointegration and bacterial resistance without compromising bulk mechanical properties. This study demonstrates the ease with which significant changes to Si3N4's surface phase composition, charging, and wetting behavior can be induced, and represents an initial step towards a mechanistic understanding of the interaction between implant surfaces and the biologic environment.

Three-dimensional zinc incorporated borosilicate bioactive glass scaffolds for rodent critical-sized calvarial defects repair and regeneration.

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.

Wound dressings composed of copper-doped borate bioactive glass microfibers stimulate angiogenesis and heal full-thickness skin defects in a rodent model.

There is a need for better wound dressings that possess the requisite angiogenic capacity for rapid in situ healing of full-thickness skin wounds. Borate bioactive glass microfibers are showing a remarkable ability to heal soft tissue wounds but little is known about the process and mechanisms of healing. In the present study, wound dressings composed of borate bioactive glass microfibers (diameter = 0.4-1.2 µm; composition 6Na2O, 8K2O, 8MgO, 22CaO, 54B2O3, 2P2O5; mol%) doped with 0-3.0 wt.% CuO were created and evaluated in vitro and in vivo. When immersed in simulated body fluid, the fibers degraded and converted to hydroxyapatite within ∼7 days, releasing ions such as Ca, B and Cu into the medium. In vitro cell culture showed that the ionic dissolution product of the fibers was not toxic to human umbilical vein endothelial cells (HUVECs) and fibroblasts, promoted HUVEC migration, tubule formation and secretion of vascular endothelial growth factor (VEGF), and stimulated the expression of angiogenic-related genes of the fibroblasts. When used to treat full-thickness skin defects in rodents, the Cu-doped fibers (3.0 wt.% CuO) showed a significantly better capacity to stimulate angiogenesis than the undoped fibers and the untreated defects (control) at 7 and 14 days post-surgery. The defects treated with the Cu-doped and undoped fibers showed improved collagen deposition, maturity and orientation when compared to the untreated defects, the improvement shown by the Cu-doped fibers was not markedly better than the undoped fibers at 14 days post-surgery. These results indicate that the Cu-doped borate glass microfibers have a promising capacity to stimulate angiogenesis and heal full-thickness skin defects. They also provide valuable data for understanding the role of the microfibers in healing soft tissue wounds.

Evaluation of injectable strontium-containing borate bioactive glass cement with enhanced osteogenic capacity in a critical-sized rabbit femoral condyle defect model.

The development of a new generation of injectable bone cements that are bioactive and have enhanced osteogenic capacity for rapid osseointegration is receiving considerable interest. In this study, a novel injectable cement (designated Sr-BBG) composed of strontium-doped borate bioactive glass particles and a chitosan-based bonding phase was prepared and evaluated in vitro and in vivo. The bioactive glass provided the benefits of bioactivity, conversion to hydroxyapatite, and the ability to stimulate osteogenesis, while the chitosan provided a cohesive biocompatible and biodegradable bonding phase. The Sr-BBG cement showed the ability to set in situ (initial setting time = 11.6 ± 1.2 min) and a compressive strength of 19 ± 1 MPa. The Sr-BBG cement enhanced the proliferation and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells in vitro when compared to a similar cement (BBG) composed of chitosan-bonded borate bioactive glass particles without Sr. Microcomputed tomography and histology of critical-sized rabbit femoral condyle defects implanted with the cements showed the osteogenic capacity of the Sr-BBG cement. New bone was observed at different distances from the Sr-BBG implants within eight weeks. The bone-implant contact index was significantly higher for the Sr-BBG implant than it was for the BBG implant. Together, the results indicate that this Sr-BBG cement is a promising implant for healing irregularly shaped bone defects using minimally invasive surgery.

Biocompatibility and osteogenic capacity of borosilicate bioactive glass scaffolds loaded with Fe3O4 magnetic nanoparticles.

Multifunctional biocompatible scaffolds with enhanced osteogenic capacity coupled with magnetic and magnetothermal properties are of great interest for the repair of large bone defects resulting from the resection of tumors. In the present study, we created borosilicate bioactive glass (BG) scaffolds loaded with varying amounts (5-15 wt%) of Fe3O4 magnetic nanoparticles (MNPs) and evaluated their performance in vitro and in vivo. The incorporation of MNPs endowed scaffolds with excellent magnetic, controlled magnetothermal properties and higher mechanical capacity. The MNP-loaded scaffolds were not toxic to human bone marrow-derived stem cells (hBMSCs) cultured on the scaffolds in vitro. The alkaline phosphatase activity and the osteogenic gene expression of the hBMSCs increased with increasing amount of MNPs in the scaffolds. When implanted in rat calvarial defects for 8 weeks, the scaffolds loaded with 15 wt% MNPs showed a significantly better capacity to regenerate bone when compared to the scaffolds without the MNPs. These MNP-loaded BG scaffolds are promising implants for regenerating bone in defects resulting from tumor resection.

Copper-doped borosilicate bioactive glass scaffolds with improved angiogenic and osteogenic capacity for repairing osseous defects.

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.