Facile post modification synthesis of copper-doped mesoporous bioactive glass with high antibacterial performance to fight bone infection

Successful treatment of infected bone defects caused by multi-drug resistant bacteria (MDR) has become a major clinical challenge, stressing the urgent need for effective antibacterial bone graft substitutes. Mesoporous bioactive glass nanoparticles (MBGNs), a rapidly emerging class of nanoscale biomaterials, offer specific advantages for the development of biomaterials to treat bone infection due to endowed antibacterial features. Herein, we propose a facile post-modification sol-gel strategy to synthesize effective antibacterial MBGNs doped with copper ions (Cu-PMMBGNs). In this strategy, amine functional groups as chelating agents were introduced to premade mesoporous silica nanoparticles (MSNs) which further facilitate the incorporation of high content of calcium (∼17 mol%) and copper ions (∼8 mol%) without compromising nanoparticle shape, mesoporosity, and homogeneity. The resulting nanoparticles were degradable and showed rapidly induce abundant deposition of apatite crystals on their surface upon soaking in simulated body fluids (SBF) after 3 days. Cu-PMMBGNs exhibited a dose-dependent inhibitory effect on Methicillin-resistant Staphylococcus aureus (MRSA) bacteria, which are common pathogens causing severe bone infections. Most importantly, the nanoparticles containing 5 mol% copper ions at concentrations of 500 and 1000 μg.mL−1 showed highly effective antibacterial performance as reflected by a 99.9 % reduction of bacterial viability. Nanoparticles at a concentration of 500 μg.mL−1 showed no significant cytotoxicity toward preosteoblast cells (∼85–89 % cell viability) compared to the control group. In addition, the nanoscale properties of synthesized Cu-PMMBGNs (∼100 nm in size) facilitated their internalization into preosteoblast cells, which highlights their potential as intracellular carriers in combating intracellular bacteria. Therefore, these copper-doped nanoparticles hold strong promise for use as an antibacterial component in antibacterial bone substitutes such as hydrogels, nanocomposites, and coatings.</p

Interfacial characterization of poly (vinyl alcohol) fibers embedded in a calcium phosphate cement matrix: An experimental and numerical investigation

Because of their chemical similarity to the mineral phase of bone and teeth, calcium phosphate cements (CPCs) are extensively investigated for applications in biomedicine. Nevertheless, their applicability in load-bearing anatomical sites is restricted by their brittleness. Reinforcement of calcium phosphate cements with polymeric fibers can overcome this mechanical limitation provided that the affinity between these fibers and the surrounding matrix is optimal. To date, the effects of the fiber-matrix affinity on the mechanical properties of fiber-reinforced calcium phosphate cements are still poorly understood. The goal of this study is therefore to investigate the interfacial properties and bond-slip response between the CPC matrix and polymeric fibers. To this end, we selected poly (vinyl alcohol) (PVA) fibers as reinforcing agents because of their high strength and stiffness and their effective reinforcement of cementitious matrices. Micromechanical pull-out experiments were combined with numerical simulations based on an dedicated constitutive interfacial law to characterize the interfacial properties of PVA fibers embedded in a CPC matrix at the single fiber pull-out level. The computational model developed herein is able to predict all three main phases of pull-out response, i.e. the elastic, debonding and frictional pull-out phases. The resulting interfacial constitutive law is validated experimentally and predicts the pull-out response of fibers with different diameters and embedded lengths. Statements of Significance: To date, the effects of the fiber-matrix affinity on the mechanical properties of fiber-reinforced calcium phosphate cements are still poorly understood. In this study, we present a novel experimental protocol to investigate the affinity between poly (vinyl alcohol) PVA fibers and the calcium phosphate cement (CPC) matrix by means of single-fiber pull out tests. We determine the critical embedded length for PVA fibers with two different diameters; and we design a numerical FE model including a distinct representation of fiber, matrix and interface with a predictive interfacial constitutive law which is capable of capturing all three main phases of single-fiber pull-out, i.e. elastic, debonding and frictional stages. The resulting interfacial constitutive law is validated experimentally and predicts the pull-out response of fibers with different diameters and embedded lengths

Self-Healing Materials are Coming of Age

Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Novel Aerospace Material

Electrophoretic deposition of silk fibroin coatings with pre-defined architecture to facilitate precise control over drug delivery

The therapeutic precision and clinical applicability of drug-eluting coatings can be substantially improved by facilitating tunable drug delivery. However, the design of coatings which allows for precise control over drug release kinetics is still a major challenge. Here, a double-layered silk fibroin (SF) coating system was constructed by sequential electrophoretic deposition. A mixture of dissolved Bombyx mori SF (bmSF) molecules and pre-made bmSF nanospheres at different ratios was deposited as under-layer. Subsequently, this underlayer was covered by a top-layer comprising Antheraea pernyi SF (apSF) molecules (rich in arginylglycylaspartic acid, RGD) to improve the cellular response of the resulting double-layered coatings. Additionally, model drug doxycycline was either pre-mixed with dissolved bmSF molecules or pre-loaded into pre-made bmSF nanospheres at the same amount before their mixing and deposition. The thickness and nanosphere content of the under-layer architecture were proportional to the deposition time and nanosphere concentration in precursor mixtures, respectively. The surface topography, wettability, degradation rate and adhesion strength were comparable within the double-layered coating system. As expected, RGD-rich apSF top-layer improved cell adhesion, spreading and proliferation compared with bmSF top-layer. Furthermore, the amount and duration of drug release increased linearly with increasing nanosphere concentration at fixed deposition time, whereas drug release amount increased linearly with increasing deposition time. These results indicate that the dosage and kinetics of loaded drugs can be quantitatively tailored by altering nanosphere concentration and deposition time as main processing parameters. Overall, this study illustrates the strong potential of pre-defining coating architecture to facilitate control over drug delivery

Experimental and numerical analysis on bending and tensile failure behavior of calcium phosphate cements

Since their discovery in the 1980s, injectable self-setting calcium phosphate cements (CPCs) are frequently used in orthopedic, oral and maxillofacial surgery due to their chemical resemblance to the mineral phase of native bone. However, these cements are very brittle, which complicates their application in load-bearing anatomical sites. Polymeric fibers can be used to transform brittle calcium phosphate cements into ductile and load-bearing biomaterials. To understand and optimize this process of fiber reinforcement, it is essential to characterize the mechanical properties of fiber-free calcium phosphate matrices in full detail. However, the mechanical performance of calcium phosphate cements is usually tested under compression only, whereas bending and tensile tests are hardly performed due to technical limitations. In addition, computational models describing failure behavior of calcium phosphate cements under these clinically more relevant loading scenarios have not yet been developed. Here, we investigate the failure behavior of calcium phosphate cements under bending and tensile loading by combining, for the first time, experimental tests and numerical modeling. To this end, a 3-D gradient-enhanced damage model is developed in a finite element framework, and numerical results are correlated to experimental three-point bending and tensile tests to characterize the mechanical properties of calcium phosphate cements in full detail. The presented computational model is successfully validated against experimental results and is able to predict the mechanical response of calcium phosphate cement under different types of loading with a unique set of parameters. This model offers a solid basis for further experimental and computational studies on the development of load-bearing bone cements.Applied MechanicsMaterials- Mechanics- Management & Desig

Interfacial characterization of poly (vinyl alcohol) fibers embedded in a calcium phosphate cement matrix: An experimental and numerical investigation

Because of their chemical similarity to the mineral phase of bone and teeth, calcium phosphate cements (CPCs) are extensively investigated for applications in biomedicine. Nevertheless, their applicability in load-bearing anatomical sites is restricted by their brittleness. Reinforcement of calcium phosphate cements with polymeric fibers can overcome this mechanical limitation provided that the affinity between these fibers and the surrounding matrix is optimal. To date, the effects of the fiber-matrix affinity on the mechanical properties of fiber-reinforced calcium phosphate cements are still poorly understood. The goal of this study is therefore to investigate the interfacial properties and bond-slip response between the CPC matrix and polymeric fibers. To this end, we selected poly (vinyl alcohol) (PVA) fibers as reinforcing agents because of their high strength and stiffness and their effective reinforcement of cementitious matrices. Micromechanical pull-out experiments were combined with numerical simulations based on an dedicated constitutive interfacial law to characterize the interfacial properties of PVA fibers embedded in a CPC matrix at the single fiber pull-out level. The computational model developed herein is able to predict all three main phases of pull-out response, i.e. the elastic, debonding and frictional pull-out phases. The resulting interfacial constitutive law is validated experimentally and predicts the pull-out response of fibers with different diameters and embedded lengths. Statements of Significance: To date, the effects of the fiber-matrix affinity on the mechanical properties of fiber-reinforced calcium phosphate cements are still poorly understood. In this study, we present a novel experimental protocol to investigate the affinity between poly (vinyl alcohol) PVA fibers and the calcium phosphate cement (CPC) matrix by means of single-fiber pull out tests. We determine the critical embedded length for PVA fibers with two different diameters; and we design a numerical FE model including a distinct representation of fiber, matrix and interface with a predictive interfacial constitutive law which is capable of capturing all three main phases of single-fiber pull-out, i.e. elastic, debonding and frictional stages. The resulting interfacial constitutive law is validated experimentally and predicts the pull-out response of fibers with different diameters and embedded lengths.Accepted Author ManuscriptApplied MechanicsMaterials- Mechanics- Management & Desig