Bioactive Glass Scaffolds Research Articles

Making foam-like bioactive glass scaffolds by vat photopolymerization

This study explores the feasibility of bioactive glass scaffolds by using a stereolithographic technology (digital light processing-based vat photopolymerization) as fabrication method and the micro-tomographic reconstruction of an open-cell polymeric sponge as input virtual model to the printing system, in the attempt to replicate the trabecular architecture of cancellous bone. Additively-manufactured scaffolds were investigated from morphological (scanning electron microscopy), microstructural (X-ray diffraction), mechanical (compressive tests) and bioactive viewpoints (immersion studies in simulated body fluid (SBF)). Well-densified foam-like glass scaffolds were obtained after sintering, provided with suitable mechanical properties (compressive strength 21.9 ± 6.2 MPa, elastic modulus 4.8 ± 0.1 GPa, Weibull modulus 3.9) for bone-contact applications. The formation of a hydroxyapatite layer on scaffold struts after soaking in SBF also demonstrated the in vitro bioactivity of the printed structures.

3D-printed mesoporous bioactive glass scaffolds for enhancing bone repair via synergetic angiogenesis and osteogenesis

Blood vessels play an important role in bone growth and fracture healing by providing nutrients and oxygen. Although great progress has been made in bone graft materials with good biological and physicochemical properties, vascularization of these materials remains an urgent challenge for bone regeneration. Herein, we report a novel 3D-printed mesoporous bioactive glass (MBG) scaffold (ICA/TMP@MBG) incorporating two unique extracts from Chinese medicine, namely tetramethylpyrazine (TMP) and icariin (ICA), for enhanced vascularization and bone repair. In vitro results showed that ICA/TMP@MBG could significantly upregulate VEGF secretion, thereby facilitating the formation of angiogenesis tubes in human umbilical vein endothelial cells (HUVECs). On the other hand, it can also promote the osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) by stimulating the expression of OPN, ALP, OCN and BMP-2. In addition, in vivo tests further demonstrated that ICA/TMP@MBG could significantly enhance vascularization and accelerate bone healing in a mouse skull defect model. Therefore, the 3D-printed ICA/TMP@MBG has great potential to promote angiogenesis and osteogenesis in bone regeneration.

Two-dimensional molybdenum disulfide/polymer-coated bioactive glass scaffolds for tissue engineering: Fabrication, structural, mechanical, bioactivity, and radiation interaction properties

Molybdenum disulfide (MoS2)-based nanostructures are widely used in environmental protection and biomedicine owing to their biological, physical, chemical, electrical, and mechanical properties. In this study, polycaprolactone (PCL)- and polylactide-co-glycolide (PLGA)-coated bioactive glass scaffolds containing MoS2 nanoparticles are prepared, and their usability in bone tissue engineering applications is evaluated. Borate bioactive glass scaffolds are fabricated using the replication method and coated with PCL or PLGA solutions (5 wt%) containing MoS2 (0.1, 0.2, 0.5, 1, and 2 wt%) nanoparticles. The structural and mechanical properties of the scaffolds and their bioactivity in simulated body fluids are investigated comprehensively. The ionization–radiation-shielding properties are investigated using Monte Carlo simulations. The results show that the polymer coating layer and presence of MoS2 nanoparticles in the polymer matrix improves the mechanical properties of the scaffolds. The addition of MoS2 nanoparticles to the structure increases the hydroxyapatite-forming ability of bioactive glass-based composites. Additionally, the prepared composite scaffolds exhibit high radiation-shielding ability owing to the presence of MoS2 nanoparticles embedded in the polymer matrix that shields the glass surface. Bioactive glass composite scaffolds containing MoS2 nanoparticles demonstrate promising potential for bone regeneration and radiation-shielding applications.

Impact of borosilicate bioactive glass scaffold processing and reactivity on in-vitro dissolution properties

In this study, bulk borosilicate glasses and 3D scaffolds (processed by the burn-off technique and by robocasting) were synthesized to investigate the impact of the manufacturing method, glass composition and preincubation time on in vitro dissolution and cell response. The studied compositions are based on commercial bioactive glass S53P4 (BonAlive) where 12.5% SiO2 has been replaced by B2O (labelled B12.5), and part of the CaO is replaced with MgO and SrO (labelled B12.5-Mg-Sr). First, the impact of the processing and glass composition, on the dissolution rate, was assessed. As expected, scaffolds were found to exhibit faster dissolution, due to the increased surface area, when compared to the bulk glass. Furthermore, the 3D printed scaffolds were found to dissolve faster than the burn-off scaffolds. Moreover, scaffolds made from B12.5-Mg-Sr glass composition exhibited slower ion release and precipitation of calcium phosphate (CaP) layer, when compared to B12.5, due to the stabilizing effect of Mg and Sr. Finally, dynamic condition produces lower ion releases that static condition and could be more optimal for in vitro cell growth. Secondly, in culture with murine MC3T3-E1 cells, it was shown that 3 days preincubation would be optimal to decrease the burst of ions that is known to lead to cell death. However, it was found that MC3T3-E1 survived and proliferated only in presence of B12.5-Mg-Sr scaffolds. Finally, it was shown that despite scaffolds having different porosities, they had no significant difference on human adipose-derived stem cells (hADSCs) survival. This manuscript brings new information on 1) the impact of material design (porosity) and composition on dissolution kinetic sand reactivity, 2) the impact of static vs dynamic testing on in-vitro dissolution and 3) the impact of materials’ pre-incubation on cell behavior.

Design of bioglasses/PDLLA scaffolds with responsive drug delivery in ultrasonic-assisted bone repair

Low-intensity pulsed ultrasound (LIPUS) assisted bone repair is confirmed effective in clinic. Here, a 3D-printed composite poly(DL-lactic acid)/mesoporous bioactive glass scaffold was constructed for particular use in LIPUS-assisted bone tissue engineering. The scaffolds contain dimethyloxallyl glycine (DMOG) loaded microbubbles in pores, which can be released after implanting via LIPUS stimulation. Local DMOG concentrations are modulated through ultrasound power and processing time. The rat bone marrow-derived mesenchymal stem cells (rBMSCs) on these scaffolds with ultrasound treatment show improved proliferation and early osteogenic differentiation.

3D-printed strontium-doped BG-CaSiO3-HA composite scaffolds promote critical bone defect repair by improving mechanical strength and increasing osteogenic activity

The release of silicon and calcium elements contained in silicon-based materials promotes the formation of bone. For bioactive glass prepared by the sol-gel method, water-soluble binders are usually added when preparing 3D printed scaffolds. However, the obtained scaffolds are prone to collapse when exposed to water and have low strength. At the same time, the binder needs to be removed for clinical applications, so the 3D printed scaffolds need to be sintered. Under high temperature, bioactive glass scaffolds will be transformed into composite scaffolds composed of bioglass, CaSiO3 and hydroxyapatite, while different sintering temperatures will form different crystal types of CaSiO3. In this study, SrBG-βCS-HA and BG-βCS-HA were obtained at a heating rate of 5 °C/min to 1100 °C and at the same rate to room temperature. SrBG-αCS-HA and BG-αCS-HA were obtained at a heating rate of 2 °C/min to 1200 °C and at the same rate to room temperature. In vitro and in vivo experiments verified that the presence of strontium in the obtained scaffolds after sintering further enhanced the osteogenic properties of the scaffolds. SrBG-αCaSiO3-HA and SrBG-βCaSiO3-HA were found to have relatively better osteogenic properties. The results show that SrBG-CaSiO3-HA 3D printing scaffolds have excellent clinical application potential.

Translated article] Design and comparison of bone substitutes. Study of in vivo behaviour in a rabbit model

AimTo compare the in vivo bone formation capacity of of biomaterials designed as bone substitutes with respect to iliac crest autograft, one based on carbonate hydroxiapatite and the other one on bioactive mesoporous glass. Materials and methodsExperimental study consisting on 14 adult female New Zeland rabbits where a critical defect was made in the rabbit radius bone. The sample was divided into four groups: defect without material, with iliac crest autograft, with carbonatehydroxyapatite scaffold, and with bioactive mesoporous glass scaffold. Serial X-ray studies were carried out at 2, 4, 6 and 12 weeks and a microCT study at euthanasia at 6 and 12 weeks. ResultsIn the X-ray study, autograft group showed the highest bone formation scores. Both groups of biomaterials presented bone formation similar and greater than the defect without material, but always less than in the autograft group. The results of the microCT study showed the largest bone volume in the study area in the autograft group. The groups with bone substitutes presented greater bone volume than the group without material but always less than the autograft group. ConclusionBoth scaffolds seem to promote bone formation but are not capable of reproducing the characteristics of autograft. Due to their different macroscopic characteristics, each one could be suitable for a different type of defect.

Evaluation of the effects of alumina nanowire on 3D printed polycaprolactone / magnetic mesoporous bioactive glass scaffold for bone tissue engineering applications

In bone tissue engineering, it is necessary to choose appropriate and efficient biomaterial for higher efficiency of the scaffold. This study used the sol-gel method to synthesise magnetic mesoporous bioactive glass (MMBG). Then, different percentage of alumina nanowire (Al2O3) were mechanically added to MMBG. After that, it was mixed with polycaprolactone (PCL) polymeric solution, and finally, the samples were printed using by Liquid Deposition Modeling (LDM) method. The results of X-ray diffraction (XRD), zeta potential, Bruner-Emmt-Teller (BET) and Vibrating Sample Magnetometer (VSM) analysis illustrated that the synthesised bioactive glass nanoparticles have a mesoporous structure with paramagnetic properties. The SEM results of the 3D printed scaffolds illustrated homogeneous structures with interconnected pores. The scaffolds' mechanical strength and contact angle were significantly improved by adding Al2O3 up to 5 wt %. Furthermore, the degradation and bioactivity of the scaffolds improved with the presence of alumina nanowires. Cell viability and proliferation of MG-63 cells and alkaline phosphatase (ALP) activity significantly increased in PCL/MMBG/5Al2O3 scaffolds compared to PCL and PCL/MMBG scaffolds. Results obtained from this study demonstrated that the 3D printed PCL/MMBG/5Al2O3 scaffold could be an acceptable candidate for bone tissue engineering applications.

Sequential Therapy for Bone Regeneration by Cerium Oxide-Reinforced 3D-Printed Bioactive Glass Scaffolds.

Rational design of multifunctional biomaterials with customized architecture and on demand bioactivity is of great significance for bone tissue engineering (BTE) in modern society. Herein, a versatile therapeutic platform has been established by integrating cerium oxide nanoparticles (CeO2 NPs) into bioactive glass (BG) to fabricate three-dimensional (3D)-printed scaffolds, achieving a sequential therapeutic effect against inflammation and promoting osteogenesis toward bone defect. The antioxidative activity of CeO2 NPs plays a crucial role in alleviating the oxidative stress upon formation of bone defects. Subsequently, CeO2 NPs exert a promotion effect on the proliferation and osteogenic differentiation of rat osteoblasts through enhancing mineral deposition and alkaline phosphatase and osteogenic gene expression. Strikingly, the incorporation of CeO2 NPs bestows on the BG scaffolds greatly reinforced mechanical properties, improved biocompatibility, adequate cell adhesion, elevated osteogenic capability, and multifunctional performance in a single platform. In vivo studies on the treatment of rat tibial defect confirmed the better osteogenic properties of CeO2-BG scaffolds compared with pure BG scaffolds. Additionally, the employment of the 3D printing technique creates a proper porous microenvironment around the bone defect, which further facilitates the cell in-growth and new bone formation. This report provides a systematic study on CeO2-BG 3D-printed scaffolds prepared by simple ball milling method, achieving sequential and integral treatment in BTE based on a single platform.

3D printed mesoporous bioactive glass, bioglass 45S5, and β-TCP scaffolds for regenerative medicine: A comparative invitro study.

While autografts to date remain the "gold standard" for bone void fillers, synthetic bone grafts have garnered attention due to their favorable advantages such as ability to be tailored in terms of their physical and chemical properties. Bioactive glass (BG), an inorganic material, has the capacity to form a strong bond with bone by forming a bone-like apatite surface, enhancing osteogenesis. Coupled with additive manufacturing (3D printing) it is possible to maximize bone regenerative properties of the BG. The objective of this study was to synthesize and characterize 3D printed mesoporous bioactive glass (MBG), BG 45S5, and compare to β-Tricalcium phosphate (β-TCP) based scaffolds; test cell viability and osteogenic differentiation on human osteoprogenitor cells invitro. MBG, BG 45S5, and β-TCP were fabricated into colloidal gel suspensions, tested with a rheometer, and manufactured into scaffolds using a 3D direct-write micro-printer. The materials were characterized in terms of microstructure and composition with Thermogravimetric Analyzer/Differential Scanning Calorimeter (TGA/DSC), Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Micro-Computed Tomography (μ-CT), Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDS), and Mattauch-Herzog-Inductively Coupled Plasma-Mass Spectrometry (MH-ICP-MS). Scaffolds were tested for cell proliferation and osteogenic differentiation using human osteoprogenitor cells. Osteogenic media was used for differentiation, and immunocytochemistry for osteogenic markers Runx-2, Collagen-I, and Osteocalcin. The cell viability results after 7 days of culture yielded significantly higher (p < 0.05) results in β-TCP scaffolds compared to BG 45S5 and MBG groups. All materials expressed osteogenic markers after 21 days of culture in expansion and osteogenic media.

Fabrication of bioactive glass scaffolds by stereolithography: Influence of particle size and surfactant concentration

For decades, bioactive glass (BAG) has been utilized as a competent bone substitute owing to its intrinsic properties, such as outstanding biocompatibility and bioresorbability. Stereolithography (SL) is an additive manufacturing technology used to produce highly accurate three-dimensional BAG-based bone substitutes. However, the preparation of BAG-based SL resin is always a challenge, especially because of the inevitable sedimentation of BAG particles. In this study, BAG particles with different sizes were prepared by dry grinding (BAGdry, greater particle size) and wet grinding (BAGwet, finer particle size). Then, BAGdry or BAGwet SL resins with various amounts of surfactant were analyzed. The sedimentation rate for BAG powder increased with increasing particle size but decreased with increasing amounts of surfactant added to the resin. BAGwet SL resins had a longer shelf life, so printing could still be finished after 14 days, whereas BAGdry SL resins were no longer useable after 5 days. However, the BAG particle size did not affect the printing accuracy or scaffold strength. According to our results, BAG-based SL resin fabricated with BAGwet (particle size <1.6 μm) and 5 wt% surfactant exhibited better resistance to sedimentation.

Bismuth-coated 80S15C bioactive glass scaffolds for photothermal antitumor therapy and bone regeneration.

Background: Malignant bone tumors usually occur in young people and have a high mortality and disability rate. Surgical excision commonly results in residual bone tumor cells and large bone defects, and conventional radiotherapy and chemotherapy may cause significant side effects. In this study, a bifunctional Bi-BG scaffold for near-infrared (NIR)-activated photothermal ablation of bone tumors and enhanced bone defect regeneration is fabricated. Methods: In this study, we prepared the Bi-BG scaffold by in-situ generation of NIR-absorbing Bi coating on the surface of a 3D-printing bioactive glass (BG) scaffold. SEM was used to analyze the morphological changes of the scaffolds. In addition, the temperature variation was imaged and recorded under 808nm NIR laser irradiation in real time by an infrared thermal imaging system. Then, the proliferation of rat bone mesenchymal stem cells (rBMSCs) and Saos-2 on the scaffolds was examined by CCK-8 assay. ALP activity assay and RT-PCR were performed to test the osteogenic capacity. For in vivo experiments, the nude rat tumor-forming and rat calvarial defect models were established. At 8weeks after surgery, micro-CT, and histological staining were performed on harvested calvarial samples. Results: The Bi-BG scaffolds have outstanding photothermal performance under the irradiation of 808nm NIR at different power densities, while no photothermal effects are observed for pure BG scaffolds. The photothermal temperature of the Bi-BG scaffold can be effectively regulated in the range 26-100°C by controlling the NIR power density and irradiation duration. Bi-BG scaffolds not only significantly induces more than 95% of osteosarcoma cell death (Saos-2) in vitro, but also effectively inhibit the growth of bone tumors in vivo. Furthermore, they exhibit excellent capability in promoting osteogenic differentiation of rBMSCs and finally enhance new bone formation in the calvarial defects of rats. Conclusion: The Bi-BG scaffolds have bifunctional properties of photothermal antitumor therapy and bone regeneration, which offers an effective method to ablate malignant bone tumors based on photothermal effect.

Dissolution of Glass–Ceramic Scaffolds of Bioactive Glasses 45S5 and S53P4

Although the initial in vitro dissolution of bioactive glasses (BAG) is well characterized, the long-term behaviour of crystallized BAG scaffolds in a continuous fluid flow is incompletely understood. A detailed understanding of the long-term dissolution of scaffolds is vital for predicting their behaviour in clinical applications. Here, we explored the dissolution and reaction mechanisms of partly crystalline and glass–ceramic scaffolds based on the bioactive glasses S53P4 and 45S5 using a continuous flow-through method in Tris-buffer (Tris) and simulated body fluid (SBF) for up to 21 days. Granules of the parent glasses were used as references. The main crystalline phase in both scaffolds was sodium-calcium-silicate. The scaffolds’ dissolution suggested that the sodium-calcium-silicate crystals dissolved incongruently to yield hydrous silica. The silica phase then provided abundant nucleation sites for hydroxyapatite precipitation, resulting in fine-grained crystalline structures. When exposed to Tris, the scaffolds almost completely dissolved within the test period, leaving only highly porous remnant phases. For the 45S5 scaffolds, the calcium phosphate reaction layers that formed on their surfaces effectively slowed the dissolution in SBF. In contrast, this effect was less apparent for the S53P4 specimens.

Compromised osteogenic effect of exosomes internalized by senescent bone marrow stem cells via endocytoses involving clathrin, macropinocytosis and caveolae.

Stem cell senescence leads to progressive functional declines and disrupts the physiological homeostasis of bone environment. Stem cell-derived exosomes are emerging as promising therapeutical approaches to treat diverse aging-related osseous diseases. Herein, a previously reported osteoinductive exosome (OI-exo) was applied as a therapeutic agent for bone repair in aging individuals and its internalization mechanisms in senescent bone marrow stem cells (BMSCs) were explored. The results demonstrated that OI-exos derived from young BMSCs could partially rescue the proliferation, osteogenic differentiation and alleviate aging phenotypes in vitro. OI-exo-delivered hierarchical mesoporous bioactive glass (MBG) scaffold effectively promote in vivo bone formation in aging rat cranial defect model. However, the osteogenic effects of OI-exo both in vitro and in vivo were compromised in senescent individuals and for aging BMSCs compared to younger ones. This study revealed that non-senescent BMSCs internalized exosomes exclusively via clathrin-mediated endocytosis, while senescent BMSCs additionally evoked macropinocytosis and caveolae-mediated endocytosis to mediate the internalization of exosomes. The alteration of endocytic manner of senescent BMSCs and the involvement of macropinocytosis might be responsible for the compromised effects of therapeutical exosomes. The phenomena discovered in this study could also be extended to other scenarios where drugs or treatments exerted compromised effects in aging individuals. The influence of endocytic manner, avoidance of macropinocytosis-related negative effects should be taken into considerations in future therapeutic design for aging populations.

Bioceramic and polycationic biopolymer nanocomposite scaffolds for improved wound self-healing and anti-inflammatory properties: an in vitro study.

The development of wound healing scaffolds with high porosity, rapid healing properties, and anti-inflammatory functionality is vital in the chronic wound healing stage for the production of extracellular matrices of injured tissues. The 45S5 bioactive glass (BG) possesses good biocompatibility and provides a potential bonding resource for fibroblast cell proliferation, growth factor synthesis, and granulated tissue formation. Chitosan, a natural polymer, promotes tissue regeneration and has anti-microbial properties. BG and chitosan scaffolds were prepared by the freeze-drying (lyophilization) method. The chitosan scaffold is a semi-crystalline polymer with a random crystal structure because it contains more hydroxyl groups. Chitosan alone shows a sheet-like morphology with a porous microstructure (1.7475 nm). BG particulates were well decorated over the surface of the chitosan scaffold with a homogeneous dispersion. Cell viability was observed for L929 cells on the chitosan-BG scaffolds. Confocal images vividly depict the interaction of the L929 cells with the scaffold without causing any damage to the cell membrane. In vitro scratch assay shows the best wound healing activity (complete wound closure) for the BG-chitosan nanocomposite scaffolds at 18 h. The chitosan-BG scaffolds were combined with anti-inflammatory drugs and induced inflammatory genes at an inhibition rate of COX of (36, 28, and 30%), LOX of (20, 13, and 14%), and NO of (48, 38, and 39%) for chitosan, chitosan-BG, and chitosan-BG (Na-free) at 100 μL addition. The in vitro bioactivities proved that the chitosan-BG scaffolds could enable better cell formation, and exhibited improved biocompatibility, and anti-inflammatory and wound healing properties.

Preparation, Characterization, and Drug Delivery of Hexagonal Boron Nitride-Borate Bioactive Glass Biomimetic Scaffolds for Bone Tissue Engineering

In this study, biomimetic borate-based bioactive glass scaffolds containing hexagonal boron nitride hBN nanoparticles (0.1, 0.2, 0.5, 1, and 2% by weight) were manufactured with the polymer foam replication technique to be used in hard tissue engineering and drug delivery applications. To create three-dimensional cylindrical-shaped scaffolds, polyurethane foams were used as templates and covered using a suspension of glass and hBN powder mixture. Then, a heat treatment was applied at 570 °C in an air atmosphere to remove the polymer foam from the structure and to sinter the glass structures. The structural, morphological, and mechanical properties of the fabricated composites were examined in detail. The in vitro bioactivity of the prepared composites was tested in simulated body fluid, and the release behavior of gentamicin sulfate and 5-fluorouracil from glass scaffolds were analyzed separately as a function of time. The cytotoxicity was investigated using osteoblastic MC3T3-E1 cells. The findings indicated that the hBN nanoparticles, up to a certain concentration in the glass matrix, improved the mechanical strength of the glass scaffolds, which mimic the cancellous bone. Additionally, the inclusion of hBN nanoparticles enhanced the in vitro hydroxyapatite-forming ability of bioactive glass composites. The presence of hBN nanoparticles accelerated the drug release rates of the system. It was concluded that bioactive glass/hBN composite scaffolds mimicking native bone tissue could be used for bone tissue repair and regeneration applications.

3D-printed β-TCP/S53P4 bioactive glass scaffolds coated with tea tree oil: Coating optimization, in vitro bioactivity and antibacterial properties.

Bone infection treatment is a significant challenge for the orthopedic field. 3D printing is a promising technology to produce scaffolds with customized architecture, able to stimulate and support bone growth. β-TCP and S53P4 bioactive glass (BG) are well-known biomaterials for scaffold manufacturing. However, a multifunctional scaffold, able to inhibit microbial proliferation at the defect site, is of increasing interest to avoid infection recurrence. Tea tree oil (TTO) has aroused interest as an antimicrobial agent to minimize the use of antibiotics. Therefore, combining the regenerative potential of a bioceramic with TTO's antimicrobial properties could result in a scaffold capable of stimulating tissue growth and treating infections. In this context, this study aimed to produce and characterize 3D-printed β-TCP/S53P4 BG scaffolds coated with TTO. Scaffolds morphological and chemical characterizations were carried out through XDR, SEM, and FTIR analysis. β-TCP/S53P4 BG scaffolds showed a compressive strength of ~2MPa and 53 ± 2% of porosity. The scaffolds were coated by two different procedures, using an ethanol/TTO (EtOH/TTO) and a gelatin/TTO (Gel/TTO) solution with 5, 10, and 15% (v/v) TTO. The addition of TTO decreased MG-63 cell viability for both coating groups, but the Gel/TTO group showed higher cell viability. The antibacterial activity of the coated scaffolds was evaluated against S. aureus and higher inhibition of colony formation was found for Gel/TTO group. Therefore, the coating with Gel/TTO was effective in terms of antibacterial activity and cell viability. Such Gel/TTO coated β-TCP/S53P4 BG scaffolds are proposed for antibacterial bone tissue engineering.

Poly(Glycerol Succinate) as Coating Material for 1393 Bioactive Glass Porous Scaffolds for Tissue Engineering Applications.

Aliphatic polyesters are widely used for biomedical, pharmaceutical and environmental applications due to their high biodegradability and cost-effective production. Recently, star and hyperbranched polyesters based on glycerol and ω-carboxy fatty diacids have gained considerable interest. Succinic acid and bio-based diacids similar to glycerol are regarded as safe materials according to the US Food and Drug Administration (FDA). Bioactive glass scaffolds utilized in bone tissue engineering are relatively brittle materials. However, their mechanical properties can be improved by using polymer coatings that can further control their degradation rate, tailor their biocompatibility and enhance their performance. The purpose of this study is to explore a new biopolyester poly(glycerol succinate) (PGSuc) reinforced with mesoporous bioactive nanoparticles (MSNs) as a novel coating material to produce hybrid scaffolds for bone tissue engineering. Bioactive glass scaffolds were coated with neat PGSuc, PGSuc loaded with dexamethasone sodium phosphate (DexSP) and PGSuc loaded with DexSP-laden MSNs. The physicochemical, mechanical and biological properties of the scaffolds were also evaluated. Preliminary data are provided showing that polymer coatings with and without MSNs improved the physicochemical properties of the 1393 bioactive glass scaffolds and increased the ALP activity and alizarin red staining, suggesting osteogenic differentiation potential when cultured with adipose-derived mesenchymal stem cells. PGSuc with incorporated MSNs coated onto 1393 bioactive glass scaffolds could be promising candidates in bone tissue engineering applications.

Antibacterial effect of 3D printed mesoporous bioactive glass scaffolds doped with metallic silver nanoparticles

The development of new biomaterials for bone tissue regeneration with high bioactivity abilities and antibacterial properties is being intensively investigated. We have synthesized nanocomposites formed by mesoporous bioactive glasses (MBGs) in the ternary SiO2, CaO and P2O5 system doped with metallic silver nanoparticles (AgNPs) that were homogenously embedded in the MBG matrices. Ag/MBG nanocomposites have been directly synthesized and silver species were spontaneously reduced to metallic AgNPs by high temperatures (700 °C) obtained of last MBG synthesis step. Three-dimensional silver-containing mesoporous bioactive glass scaffolds were fabricated showing uniformly interconnected ultrapores, macropores and mesopores. The manufacture method consisted of a combination of a single-step sol–gel route in the mesostructure directing agent (P123) presence and a biomacromolecular polymer such as (hydroxypropyl)methyl cellulose (HPMC) as the macrostructure template, followed by rapid prototyping (RP) technique. Biological properties of Ag/MBG nanocomposites were evaluated by MC3T3-E1 preosteoblastic cells culture tests and bacterial (E. coli and S. aureus) assays. The results showed that the MC3T3-E1 cells morphology was not affected while preosteoblastic proliferation decreased when the presence of silver increased. Antimicrobial assays indicated that bacterial growth inhibition and biofilm destruction were directly proportional to the increased presence of AgNPs in the MBG matrices. Furthermore, in vitro co-culture of MC3T3-E1 cells and S. aureus bacteria confirmed that AgNPs presence was necessary for antibacterial activity, and AgNPs slightly affected cell proliferation parameters. Therefore, 3D printed scaffolds with hierarchical pore structure and high antimicrobial capacity have potential applications in bone tissue regeneration. Statement of significanceThis study combines three key scientific aspects for bone tissue engineering: (i) materials with high bioactivity to repair and regenerate bone tissue that (ii) contain antibacterial agents to reduce the infection risk (iii) in the form of three-dimensional scaffolds with hierarchical porosity. Innovative methodology is described here: sol-gel method, which is employed to obtain mesoporous bioactive glass matrices doped with metallic silver nanoparticles where different polymer templates facilitate the different size scales presence, and rapid prototyping technique that provides ultra-large macroporosity according to computer-aided design. The dual scaffolds obtained are biocompatible and deliver active doses of silver capable of combating bone infections, which represent one of the most serious complications associated to surgical treatments of bone diseases and fractures.

Bone Healing in Rat Segmental Femur Defects with Graphene-PCL-Coated Borate-Based Bioactive Glass Scaffolds.

Bone is a continually regenerating tissue with the ability to heal after fractures, though healing significant damage requires intensive surgical treatment. In this study, borate-based 13-93B3 bioactive glass scaffolds were prepared though polymer foam replication and coated with a graphene-containing poly (ε-caprolactone) (PCL) layer to support bone repair and regeneration. The effects of graphene concentration (1, 3, 5, 10 wt%) on the healing of rat segmental femur defects were investigated in vivo using male Sprague–Dawley rats. Radiographic imaging, histopathological and immuno-histochemical (bone morphogenetic protein (BMP-2), smooth muscle actin (SMA), and alkaline phosphatase (ALP) examinations were performed 4 and 8 weeks after implantation. Results showed that after 8 weeks, both cartilage and bone formation were observed in all animal groups. Bone growth was significant starting from the 1 wt% graphene-coated bioactive glass-implanted group, and the highest amount of bone formation was seen in the group containing 10 wt% graphene (p < 0.001). Additionally, the presence of graphene nanoplatelets enhanced BMP-2, SMA and ALP levels compared to bare bioactive glass scaffolds. It was concluded that pristine graphene-coated bioactive glass scaffolds improve bone formation in rat femur defects.