A novel microfluidic tool for the evaluation of local drug delivery systems in simulated in vivo conditions.

A 3D-printed microfluidic tool for assessing local drug delivery systems (LDD) in simulated in vivo conditions was developed and evaluated. The device was designed considering the oral environment and dental applications, and it was fabricated with a high-precision resin 3D printer. Chitosan scaffolds loaded with different concentrations of doxycycline were used for evaluating our device. The concentration of the released drug was measured through in-line UV-VIS spectroscopy, and to verify the repeatability and accuracy of our measurements, comparisons with standard HPLC results were made (5% deviation). Cumulative drug release profiles in steady-state conditions were obtained and compared to the Weibull model. The behaviour of the LDD system in a dynamic environment was also evaluated during experiments where step changes in pH were introduced. It was demonstrated that under infection-like conditions, there is an immediate response from the polymer and a clear increase in the concentration of the released drug. Continuous flow and recirculation experiments were also conducted, revealing significant differences in the drug release profiles. Specifically, in the case of continuous flow, the quantity of the released drug is much higher due to the higher driving force for diffusion (concentration gradient). Overall, the proposed microfluidic tool proved to be ideal for evaluating LDD systems, as the in vivo microenvironment can be replicated in a better way than with currently used standard systems.

Physiologically engineered porous titanium/brushite scaffolds for critical-size bone defects: A design and manufacturing study.

Repairing critical-size bone defects still represents a critical clinical challenge in the field of trauma surgery. This study focuses on a physiological design and manufacturing of porous composite scaffold (titanium Ti with 10 % mole iron doped brushite DCPD-Fe3+) which can mimic the biomechanical properties of natural cortical bone, specifically for the purpose of repairing critical-size defects. To achieve this, the principle of design of experiments (DOE) was applied for investigating the impact of sintering temperature, mineral ratio, and volume fraction of porosity on the mechanical properties of the fabricated scaffolds. The fabricated scaffolds had open porosity up to 60 %, with pore size approximately between 100 µm and 850 µm. The stiffness of the porous composite scaffolds varied between 3.30 GPa and 20.50 GPa, while the compressive strength ranged from approximately 130 MPa-165 MPa at sintering temperatures equal to or exceeding 1000 °C. Scaffolds with higher porosity and mineral content demonstrated lower stiffness values, resembling natural bone. Numerical simulation was employed by Ansys Workbench to investigate the stress and strain distribution of a critical size defect in mid-shaft femur which was designed to be replaced with the fabricated scaffold. The fabricated scaffolds showed flexible biomechanical behaviour at the bone/scaffold interface, generating lower stress levels and indicating a better match with the femoral shaft stiffness. The experimental and numerical findings demonstrated promising applications for manufacturing a patient-specific bone scaffold for critical and potentially large defects for reducing stress shielding and minimizing non-union risk.

Composite PLGA-Nanobioceramic Coating on Moxifloxacin-Loaded Akermanite 3D Porous Scaffolds for Bone Tissue Regeneration.

Silica-based ceramics doped with calcium and magnesium have been proposed as suitable materials for scaffold fabrication. Akermanite (Ca2MgSi2O7) has attracted interest for bone regeneration due to its controllable biodegradation rate, improved mechanical properties, and high apatite-forming ability. Despite the profound advantages, ceramic scaffolds provide weak fracture resistance. The use of synthetic biopolymers such as poly(lactic-co-glycolic acid) (PLGA) as coating materials improves the mechanical performance of ceramic scaffolds and tailors their degradation rate. Moxifloxacin (MOX) is an antibiotic with antimicrobial activity against numerous aerobic and anaerobic bacteria. In this study, silica-based nanoparticles (NPs) enriched with calcium and magnesium, as well as copper and strontium ions that induce angiogenesis and osteogenesis, respectively, were incorporated into the PLGA coating. The aim was to produce composite akermanite/PLGA/NPs/MOX-loaded scaffolds through the foam replica technique combined with the sol-gel method to improve the overall effectiveness towards bone regeneration. The structural and physicochemical characterizations were evaluated. Their mechanical properties, apatite forming ability, degradation, pharmacokinetics, and hemocompatibility were also investigated. The addition of NPs improved the compressive strength, hemocompatibility, and in vitro degradation of the composite scaffolds, resulting in them keeping a 3D porous structure and a more prolonged release profile of MOX that makes them promising for bone regeneration applications.

Synthesis and Study of Fully Biodegradable Composites Based on Poly(butylene succinate) and Biochar.

Biodegradable polymers offer a promising alternative to the global plastic problems and especially in the last decade, to the microplastics problems. For the first time, samples of poly(butylene succinate) (PBSu) biocomposites containing 1, 2.5, and 5 wt% biochar (BC) were prepared by in situ polymerization via the two-stage melt polycondensation procedure. BC was used as a filler for the PBSu to improve its mechanical properties, thermal transitions, and biodegradability. The structure of the synthesized polymers was examined by 1H and 13C nuclear magnetic resonance (NMR) and X-Ray diffraction (XRD) along with an estimation of the molecular weights, while differential scanning calorimetry (DSC) and light flash analysis (LFA) were also employed to record the thermal transitions and evaluate the thermal conductivity, respectively. It was found that the amount of BC does not affect the molecular weight of PBSu biocomposites. The fine dispersion of BC, as well as the increase in BC content in the polymeric matrix, significantly improves the tensile and impact strengths. The DSC analysis results showed that BC facilitates the crystallization of PBSu biocomposites. Due to the latter, a mild and systematic increase in thermal diffusivity and conductivity was recorded indicating that BC is a conductive material. The molecular mobility of PBSu, local and segmental, does not change significantly in the biocomposites, whereas the BC seems to cause an increase in the overall dielectric permittivity. Finally, it was found that the enzymatic hydrolysis degradation rate of biocomposites increased with the increasing BC content.

Effect of Micro- and Nano-Lignin on the Thermal, Mechanical, and Antioxidant Properties of Biobased PLA-Lignin Composite Films.

Bio-based poly(lactic acid) (PLA) composite films were produced using unmodified soda micro- or nano-lignin as a green filler at four different contents, between 0.5 wt% and 5 wt%. The PLA-lignin composite polymers were synthesized by solvent casting to prepare a masterbatch, followed by melt mixing. The composites were then converted into films, to evaluate the effect of lignin content and size on their physicochemical and mechanical properties. Differential scanning calorimetry (DSC), supported by polarized light microscopy (PLM), infrared spectroscopy (FTIR-ATR), X-ray diffraction (XRD), and transmission electron microscopy (TEM) were employed to investigate the PLA crystallization and the interactions with Lignin (L) and Nanolignin (NL). The presence of both fillers (L and NL) had a negligible effect on the glass transition temperature (chain diffusion). However, it resulted in suppression of the corresponding change in heat capacity. This was indicative of a partial immobilization of the PLA chains on the lignin entities, due to interfacial interactions, which was slightly stronger in the case of NL. Lignin was also found to facilitate crystallization, in terms of nucleation; whereas, this was not clear in the crystalline fraction. The addition of L and NL led to systematically larger crystallites compared with neat PLA, which, combined with the higher melting temperature, provided indications of a denser crystal structure in the composites. The mechanical, optical, antioxidant, and surface properties of the composite films were also investigated. The tensile strength and Young's modulus were improved by the addition of L and especially NL. The UV-blocking and antioxidant properties of the composite films were also enhanced, especially at higher filler contents. Importantly, the PLA-NL composite films constantly outperformed their PLA-L counterparts, due to the finer dispersion of NL in the PLA matrix, as verified by the TEM micrographs. These results suggest that bio-based and biodegradable PLA films filled with L, and particularly NL, can be employed as competitive and green alternatives in the food packaging industry.

Dicalcium Phosphate Dihydrate Mineral Loaded Freeze-Dried Scaffolds for Potential Synthetic Bone Applications.

Dicalcium Phosphate Dihydrate (DCPD) mineral scaffolds alone do not possess the mechanical flexibility, ease of physicochemical properties' tuneability or suitable porosity required for regenerative bone scaffolds. Herein, we fabricated highly porous freeze-dried chitosan scaffolds embedded with different concentrations of Dicalcium Phosphate Dihydrate (DCPD) minerals, i.e., 0, 20, 30, 40 and 50 (wt)%. Increasing DCPD mineral concentration led to increased scaffold crystallinity, where the % crystallinity for CH, 20, 30, 40, and 50-DCPD scaffolds was determined to be 0.1, 20.6, 29.4, 38.8 and 69.9%, respectively. Reduction in scaffold pore size distributions was observed with increasing DCPD concentrations of 0 to 40 (wt)%; coalescence and close-ended pore formation were observed for 50-DCPD scaffolds. 50-DCPD scaffolds presented five times greater mechanical strength than the DCPD mineral-free scaffolds (CH). DCPD mineral enhanced cell proliferation for the 20, 30 and 40-DCPD scaffolds. 50-DCPD scaffolds presented reduced pore interconnectivity due to the coalescence of many pores in addition to the creation of closed-ended pores, which were found to hinder osteoblast cell proliferation.

Sol-Gel Synthesis and Characterization of YSZ Nanofillers for Dental Cements at Different Temperatures.

BACKGROUND: Yttria-stabilized zirconia nanoparticles can be applied as fillers to improve the mechanical and antibacterial properties of luting cement. The aim of this study was to synthesize yttria-stabilized zirconia nanoparticles by the sol-gel method and to investigate their composition, structure, morphology and biological properties. METHODS: Nanopowders of ZrO2 7 wt% Y2O3 (nY-ZrO) were synthesized by the sol-gel method and were sintered at three different temperatures: 800, 1000 and 1200 °C, and their composition, size and morphology were investigated. The biocompatibility was investigated with human gingival fibroblasts (hGFs), while reactive oxygen species (ROS) production was evaluated through fluorescence analysis. RESULTS: All synthesized materials were composed of tetragonal zirconia, while nanopowders sintered at 800 °C and 1000 °C additionally contained 5 and 20 wt% of the cubic phase. By increasing the calcination temperature, the crystalline size of the nanoparticles increased from 12.1 nm for nY-ZrO800 to 47.2 nm for nY-ZrO1200. Nano-sized particles with good dispersion and low agglomeration were received. Cell culture studies with human gingival fibroblasts verified the nanopowders' biocompatibility and their ROS scavenging activity. CONCLUSIONS: the obtained sol-gel derived nanopowders showed suitable properties to be potentially used as nanofillers for dental luting cement.

Interrelationships between the structural, spectroscopic, and antibacterial properties of nanoscale (< 50 nm) cerium oxides.

Bone healing is a complex process, and if not managed successfully, it can lead to non-union, metal-work failure, bacterial infections, physical and psychological patient impairment. Due to the growing urgency to minimise antibiotic dependency, alternative treatment strategies, including the use of nanoparticles, have attracted significant attention. In the present study, cerium oxide nanoparticles (Ce4+, Ce3+) have been selected due to their unique antibacterial redox capability. We found the processing routes affected the agglomeration tendency, particle size distribution, antibacterial potential, and ratio of Ce3+:Ce4+ valence states of the cerium oxide nanoparticles. The antibacterial efficacy of the nanoparticles in the concentration range of 50-200 µg/ml is demonstrated against Escherichia coli, Staphylococcus epidermis, and Pseudomonas aeruginosa by determining the half-maximal inhibitory concentration (IC50). Cerium oxide nanoparticles containing a more significant amount of Ce3+ ions, i.e., FRNP, exhibited 8.5 ± 1.2%, 10.5 ± 4.4%, and 13.8 ± 5.8% increased antibacterial efficacy compared with nanoparticles consisting mainly of Ce4+ ions, i.e., nanoparticles calcined at 815 °C.

Synthesis and Characterization of Mesoporous Mg- and Sr-Doped Nanoparticles for Moxifloxacin Drug Delivery in Promising Tissue Engineering Applications.

Mesoporous silica-based nanoparticles (MSNs) are considered promising drug carriers because of their ordered pore structure, which permits high drug loading and release capacity. The dissolution of Si and Ca from MSNs can trigger osteogenic differentiation of stem cells towards extracellular matrix calcification, while Mg and Sr constitute key elements of bone biology and metabolism. The aim of this study was the synthesis and characterization of sol-gel-derived MSNs co-doped with Ca, Mg and Sr. Their physico-chemical properties were investigated by X-ray diffraction (XRD), scanning electron microscopy with energy dispersive X-ray analysis (SEM/EDX), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray fluorescence spectroscopy (XRF), Brunauer Emmett Teller and Brunauer Joyner Halenda (BET/BJH), dynamic light scattering (DLS) and ζ-potential measurements. Moxifloxacin loading and release profiles were assessed with high performance liquid chromatography (HPLC) cell viability on human periodontal ligament fibroblasts and their hemolytic activity in contact with human red blood cells (RBCs) at various concentrations were also investigated. Doped MSNs generally retained their textural characteristics, while different compositions affected particle size, hemolytic activity and moxifloxacin loading/release profiles. All co-doped MSNs revealed the formation of hydroxycarbonate apatite on their surface after immersion in simulated body fluid (SBF) and promoted mitochondrial activity and cell proliferation.

Mechanical and thermal properties of PMMA resin composites for interim fixed prostheses reinforced with calcium ß-pyrophosphate.

Interim restorations are essential in fixed prosthodontics as they provide temporary protection of teeth before the insertion of the permanent restoration. Poly(methyl methacrylate) (PMMA) is widely used in the fabrication of interim-fixed restorations as it is a biocompatible material with a lot of convenient properties. However, it exhibits low impact and tensile strength and therefore it is necessary to be reinforced. Calcium ß-pyrophosphate (ß-CPP) is considered a promising reinforcing material for dental applications, especially for enamel regeneration due to its stability at low pH and its low wear rate. The aim of this study was to manufacture PMMA/ß-CPP composites suitable for fixed-interim restorations and to study their mechanical and thermal properties. In order to enhance ß-CPP dispersion into PMMA matrix, ball-milling was performed for 1 or 6 h. Three-point bending test was performed to study flexural strength, Dynamic Mechanical Analysis (DMA) to reveal the elastic and viscous moduli along with Tg, Fourier Transform Infrared Spectroscopy (FTIR) and X-Ray Diffraction Analysis (XRD) to investigate the structure of the materials and SEM for the morphological evaluation of both composite powders and polymerized specimens. Thermogravimetric Analysis (TGA) and Differential Scanning Calorimetry (DSC) experiments were performed to study their thermal properties. A statistically significant increase in flexural strength was found in the 0.5, 0.75 and 1% composite groups after 6 h ball-milling, relative to the control, with the 6 h ball milling mixed specimens, presenting the highest flexural strength values. The brittle fracture type was common to all groups. An obvious improvement of the mechanical properties and a slight improvement in the thermal stability of the composite materials values were also observed as ß-CPP content was increased, while Tg values were statistically not-affected.

Analysis of the osteogenic and mechanical characteristics of iron (Fe2+/Fe3+)-doped ß­calcium pyrophosphate.

The calcium phosphate is the main mineral constituent of bone. Although there has been significant amount of research on finding ideal synthetic bone, no suitable scaffold material has yet been found. In this investigation, the iron doped brushite (CaHPO4·2H2O) has been investigated for osteogenic potential and mechanical properties. The synthesis of iron-oxide doping in the form of Fe2+,3+-ions were carried out using the solution based method in which the ammonium hydrogen phosphate and calcium nitrate solutions were used in stoichiometric ratio for synthesizing CaHPO4·2H2O, with doping concentrations of Fe2+,3+-ions between 5 mol% and 30 mol%. The synthesized powders were analysed using X-ray powder diffraction, FTIR, SEM and Raman spectroscopic techniques. The heat treatment of synthesized powder was carried out at 1000 °C in air for 5 h, and it was found that the dominant crystalline phase in samples with <20 mol% was ß-CPP, which also formed an iron-rich solid solution phase. Increasing the concentrations of Fe2+,3+-ions enhances the phase fraction of FePO4 and amorphous phase. Amongst the Fe2+,3+-doped ß-CPP minerals, it was found that the 10 mol% Fe2+,3+-doped ß-CPP offers the best combination of bio-mechanical and osteogenic properties as a scaffold for bone tissue regenerative engineering.