Strontium-releasing fluorapatite glass-ceramic scaffolds: Structural characterization and in vivo performance.

There is increasing interest in biodegradable ceramic scaffolds for bone tissue engineering capable of in situ delivery of ionic species favoring bone formation. Strontium has been shown to be osteogenic, but strontium-containing drugs such as strontium ranelate, used in Europe for the treatment of osteoporosis, are now restricted due to clinical evidence of systemic effects. By doping fluorapatite-based glasses with strontium, we developed ceramic scaffolds with fully interconnected macroporosity and cell size similar to that of cancellous bone, that are also capable of releasing strontium. The crystallization behavior, investigated by XRD and SEM, revealed the formation of akermanite and fluorapatite at the surface of strontium-free glass-ceramic scaffolds, and strontium-substituted fluorapatite at the surface of the strontium-doped scaffolds. At 8 weeks after implantation in a rat calvarial critical size defect, scaffolds doped with the highest amount of strontium led to the highest mineral apposition rate. A significantly higher amount of newly-formed bone was found with the strontium-free glass-ceramic scaffold, and possibly linked to the presence of akermanite at the scaffold surface. We demonstrate by energy dispersive XRF analyses of skull sections that strontium was present in newly formed bone with the strontium-doped scaffolds, while a significant amount of fluorine was incorporated in newly formed bone, regardless of composition or crystallization state. STATEMENT OF SIGNIFICANCE: The present work demonstrates the in vivo action of strontium-containing glass-ceramic scaffolds. These bone graft substitutes are targeted at non load-bearing bone defects. Results show that strontium is successfully incorporated in newly formed bone. This is associated with a significantly higher Mineral Apposition Rate. The benefits of in situ release of strontium are demonstrated. The broader scientific impact of this works builds on the concept of resorbable ceramic scaffolds as reservoirs of ionic species capable of enhancing bone regeneration.

Strontium-releasing fluorapatite glass-ceramics: Crystallization behavior, microstructure, and solubility.

The purpose of this work was to investigate the effect of strontium partial replacement for calcium on the crystallization behavior, microstructure and solubility of fluorapatite glass-ceramics. Four glass compositions were prepared with increasing amounts of strontium partially replacing calcium. The crystallization behavior was analyzed by differential scanning calorimetry and X-ray diffraction (XRD). The microstructure was investigated by scanning electron microscopy. The chemical solubility was quantified according to ISO standard 10993-14. The amount of strontium released in solution after incubation in TRIS-HCl or citric acid buffer was measured by atomic absorption spectroscopy. XRD analyses revealed that partially substituted strontium-fluorapatite and strontium-åkermanite crystallized after strontium additions. The lattice cell volume of both phases increased linearly with the amount of strontium in the composition. Strontium additions led to a reduction in crystal size and an increase in crystal number density. The chemical solubility and amount of strontium released in solution increased linearly with the amount of strontium present in the composition in both TRIS-HCl and citric acid buffers. Total amounts of strontium released reached a maximum of 547 ± 80 ppm in TRIS-HCl and 1252 ± 290 ppm in citric acid buffer for the glass composition with the highest amount of strontium. For all strontium-containing compositions, the amount released in TRIS-HCl continued to increase between 70 and 120 h, indicating sustained release rather than burst release. © 2017 Wiley Periodicals, Inc. J Biomater Res Part B: 106B: 1421-1430, 2018.

Rapid vacuum sintering: A novel technique for fabricating fluorapatite ceramic scaffolds for bone tissue engineering.

Macroporous bioceramic scaffolds are often fabricated via the foam replica technique, based on polymeric foam impregnation with a glass slurry, followed by slow heat treatment to allow for drying, polymeric burnout, and sintering of the glass particles. As a consequence, the process is time consuming and complicated by concurrent crystallization of the glass, often leading to incomplete sintering. Our goal was to investigate the effect of heating rate on sintering behavior, architecture, and mechanical properties of fluorapatite-based glass and glass-ceramic scaffolds. Glass scaffolds were prepared and sintered by rapid vacuum sintering (RVS) at 785°C under vacuum at a fast heating rate (55°C/min.) or without vacuum at a slow heating rate (2°C/min.). Two additional groups were further crystallized at 775°C/1 h. XRD confirmed the presence of fluorapatite for crystallized scaffolds. All groups presented interconnected porosity with a pore size in the 500 µm range. Scaffolds produced by RVS exhibited an excellent degree of sintering while scaffolds produced by slow sintering were incompletely sintered. The mean compressive strength was significantly higher for the RVS groups (1.52 ± 0.55 and 1.72 ± 0.61 MPa) compared to the slow-sintered groups (0.54 ± 0.30 and 0.45 ± 0.26 MPa). Meanwhile, the total production time was reduced by more than 12 h by using the RVS technique. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 291-299, 2018.

An experimental bioactive dental ceramic for metal-ceramic restorations: Textural characteristics and investigation of the mechanical properties.

The aim of this study was the evaluation of the textural characteristics of an experimental sol-gel derived feldspathic dental ceramic, which has already been proven bioactive and the investigation of its flexural strength through Weibull Statistical Analysis. The null hypothesis was that the flexural strength of the experimental and the commercial dental ceramic would be of the same order, resulting in a dental ceramic with apatite forming ability and adequate mechanical integrity. Although the flexural strength of the experimental ceramics was not statistically significant different compared to the commercial one, the amount of blind pores due to processing was greater. The textural characteristics of the experimental ceramic were in accordance with the standard low porosity levels reported for dental ceramics used for fixed prosthetic restorations. Feldspathic dental ceramics with typical textural characteristics and advanced mechanical properties as well as enhanced apatite forming ability can be synthesized through the sol-gel method.

Sol-gel processing of novel bioactive Mg-containing silicate scaffolds for alveolar bone regeneration.

Periodontal tissue regeneration is an important application area of biomaterials, given the large proportion of the population affected by periodontal diseases like periodontitis. The aim of this study was the synthesis of a novel porous bioceramic scaffold in the SiO2-CaO-MgO system with specific properties targeted for alveolar bone tissue regeneration using a modification of the traditional foam replica technique. Since bioceramic scaffolds are considered brittle, scaffolds were also coated with gelatin in order to increase their mechanical stability. Gelatin was chosen for its biocompatibility, biodegradability, low-cost, and low immunogenicity. However, gelatin degrades very fast in water solutions. For this reason, two different cross-linking agents were evaluated. Genipin, a non-toxic gardenia extract and the chemical compound 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) in combination with N-hydroxysuccinimide (NHS), which is also considered non-toxic. The results of the investigation indicated that all scaffolds presented an open, interconnected porosity and pores' sizes in the range of 300-600 µm, fast apatite-forming ability, biocompatibility, and suitable mechanical stability.

Electrophoretic deposition of antibiotic loaded PHBV microsphere-alginate composite coating with controlled delivery potential.

Electrophoretic deposition (EPD) technique has been developed for the fabrication of antibiotic-loaded PHBV microsphere (MS)-alginate antibacterial coatings. The composite coatings deposited from suspensions with different MS concentrations were produced in order to demonstrate the versatility of the proposed method for achieving functional coatings with tailored drug loading and release profiles. Linearly increased deposit mass with increasing MS concentrations was obtained, and MS were found to be homogeneously stabilized in the alginate matrix. Chemical composition, surface roughness and wettability of the deposited coatings were measured by Fourier transform infrared (FTIR) spectroscopy, laser profilometer and water contact angle instruments, respectively. The co-deposition mechanism was described by two separate processes according to the results of relevant measurements: (i) the deposition of alginate-adsorbed MS and (ii) the non-adsorbed alginate. Qualitative antibacterial tests indicated that MS containing coatings exhibit excellent inhibition effects against E. coli (gram-negative bacteria) after 1h of incubation. The proposed coating system combined with the simplicity of the EPD technique can be considered a promising surface modification approach for the controlled in situ delivery of drug or other biomolecules.

Antibacterial 45S5 Bioglass®-based scaffolds reinforced with genipin cross-linked gelatin for bone tissue engineering.

45S5 Bioglass® (BG) scaffolds with high porosity (>90%) were coated with genipin cross-linked gelatin (GCG) and further incorporated with poly(p-xylyleneguanidine) hydrochloride (PPXG). The obtained GCG coated scaffolds maintained the high porosity and well interconnected pore structure. A 26-fold higher compressive strength was provided to 45S5 BG scaffolds by GCG coating, which slightly retarded but did not inhibit the in vitro bioactivity of 45S5 BG scaffolds in SBF. Moreover, the scaffolds were made antibacterial against both Gram-positive and Gram-negative bacteria by using polyguanidine, i.e. PPXG, in this study. Osteoblast-like cells (MG-63) were seeded onto PPXG and GCG coated scaffolds. PPXG was biocompatible with MG-63 cells at a low concentration (10 µg mL-1). MG-63 cells were shown to attach and spread on both uncoated and GCG coated scaffolds, and the mitochondrial activity measurement indicated that GCG coating had no negative influence on the cell proliferation behavior of MG-63 cells. The developed novel antibacterial bioactive 45S5 BG-based composite scaffolds with improved mechanical properties are promising candidates for bone tissue engineering.

Development and characterization of magnetic iron oxide nanoparticles with a cisplatin-bearing polymer coating for targeted drug delivery.

A highly selective and efficient cancer therapy can be achieved using magnetically directed superparamagnetic iron oxide nanoparticles (SPIONs) bearing a sufficient amount of the therapeutic agent. In this project, SPIONs with a dextran and cisplatin-bearing hyaluronic acid coating were successfully synthesized as a novel cisplatin drug delivery system. Transmission electron microscopy images as well as X-ray diffraction analysis showed that the individual magnetite particles were around 4.5 nm in size and monocrystalline. The small crystallite sizes led to the superparamagnetic behavior of the particles, which was exemplified in their magnetization curves, acquired using superconducting quantum interference device measurements. Hyaluronic acid was bound to the initially dextran-coated SPIONs by esterification. The resulting amide bond linkage was verified using Fourier transform infrared spectroscopy. The additional polymer layer increased the vehicle size from 22 nm to 56 nm, with a hyaluronic acid to dextran to magnetite weight ratio of 51:29:20. A maximum payload of 330 µg cisplatin/mL nanoparticle suspension was achieved, thus the particle size was further increased to around 77 nm with a zeta potential of -45 mV. No signs of particle precipitation were observed over a period of at least 8 weeks. Analysis of drug-release kinetics using the dialysis tube method revealed that these were driven by inverse ligand substitution and diffusion through the polymer shell as well as enzymatic degradation of hyaluronic acid. The biological activity of the particles was investigated in a nonadherent Jurkat cell line using flow cytometry. Further, cell viability and proliferation was examined in an adherent PC-3 cell line using xCELLigence analysis. Both tests demonstrated that particles without cisplatin were biocompatible with these cells, whereas particles with the drug induced apoptosis in a dose-dependent manner, with secondary necrosis after prolonged incubation. In conclusion, combination of dextran-coated SPIONs with hyaluronic acid and cisplatin represents a promising approach for magnetic drug targeting in the treatment of cancer.

Electrophoretic co-deposition of polyvinyl alcohol (PVA) reinforced alginate-Bioglass® composite coating on stainless steel: mechanical properties and in-vitro bioactivity assessment.

PVA reinforced alginate-bioactive glass (BG) composite coatings were produced on stainless steel by a single step electrophoretic deposition (EPD) process. The present paper discusses the co-deposition mechanism of the three components and presents a summary of the relevant properties of the composite coatings deposited from suspensions with different PVA concentrations. Homogeneous composite coatings with compact microstructure and increased thickness, i.e. as high as 10 µm, were observed by scanning electron microscopy (SEM). The surface roughness of coatings with different PVA contents was slightly increased, while a significant increase of water contact angles due to PVA addition was detected and discussed. Improved adhesion strength of coatings containing different amounts of PVA was quantitatively and qualitatively confirmed by pull-off adhesion and cycled bending tests, respectively. In-vitro bioactivity tests were performed in simulated body fluid (SBF) for 0.5, 1, 2, 4, 7, and 14 days, respectively. The decomposition rate of the coatings was reduced with PVA content, and rapid hydroxyapatite forming ability of the composite coatings in SBF was confirmed by FTIR and XRD analyses. According to the results of this study, composite alginate-Bioglass® bioactive coatings combined with PVA are proposed as promising candidates for dental and orthopedic applications.

Antibacterial properties of metal and metalloid ions in chronic periodontitis and peri-implantitis therapy.

Periodontal diseases like periodontitis and peri-implantitis have been linked with Gram-negative anaerobes. The incorporation of various chemotherapeutic agents, including metal ions, into several materials and devices has been extensively studied against periodontal bacteria, and materials doped with metal ions have been proposed for the treatment of periodontal and peri-implant diseases. The aim of this review is to discuss the effectiveness of materials doped with metal and metalloid ions already used in the treatment of periodontal diseases, as well as the potential use of alternative materials that are currently available for other applications but have been proved to be cytotoxic to the specific periodontal pathogens. The sources of this review included English articles using Google Scholar™, ScienceDirect, Scopus and PubMed. Search terms included the combinations of the descriptors "disease", "ionic species" and "bacterium". Articles that discuss the biocidal properties of materials doped with metal and metalloid ions against the specific periodontal bacteria were included. The articles were independently extracted by two authors using predefined data fields. The evaluation of resources was based on the quality of the content and the relevance to the topic, which was evaluated by the ionic species and the bacteria used in the study, while the final application was not considered as relevant. The present review summarizes the extensive previous and current research efforts concerning the use of metal ions in periodontal diseases therapy, while it points out the challenges and opportunities lying ahead.

Bioglass®/chitosan-polycaprolactone bilayered composite scaffolds intended for osteochondral tissue engineering.

Polymer-coated 45S5 Bioglass(®) (BG)/chitosan-polycaprolactone (BG/CS-PCL) bilayered composite scaffolds were prepared via foam replication and freeze-drying techniques for application in osteochondral tissue engineering. The CS-PCL coated and uncoated BG scaffolds were characterized by X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). The mechanical properties of the coated scaffolds were significantly improved in comparison to uncoated scaffolds. The bioactivity and biodegradation behavior of scaffolds were studied in simulated body fluid (SBF) for up to 28 days. The interface between the BG scaffold and the polymer coating layer was observed by SEM and a suitable interpenetration of the polymer into the scaffold struts was found. The effects of coated and uncoated BG scaffolds on MG-63 osteoblast-like cells were evaluated by cell viability, adhesion and proliferation.

Development of bioactive glass based scaffolds for controlled antibiotic release in bone tissue engineering via biodegradable polymer layered coating.

Highly porous 45S5 Bioglass(®)-based scaffolds coated with two polymer layers were fabricated to serve as a multifunctional device with controlled drug release capability for bone regeneration applications. An interior poly(d,l-lactide)/poly(ethylene glycol)-(polypropylene glycol)-poly(ethylene glycol) triblock copolymer (Pluronic P123) coating improved the mechanical stability of Bioglass-based scaffolds, while an exterior natural polymer (alginate or gelatin) coating served as an antibiotic drug carrier. The results showed improved mechanical properties of Bioglass-based scaffolds by the bilayer polymer coating. In addition, hydrochloride tetracycline loaded in either alginate or gelatin coatings was released rapidly at the initial stage (∼1 h), while the released rate subsequently decreased and was sustained for 14 days in phosphate buffered saline. Therefore, these layered polymer coated scaffolds exhibit attractive characteristics in terms of improved mechanical properties and controlled drug release, simultaneously with the added advantage that the drug release rate is decoupled from the intrinsic scaffold Bioglass degradation mechanism. The layered polymer coated scaffolds are of interest for drug-delivery enhanced bone regeneration applications.