Synthesis and characterization of a calcium phosphate bone cement with quercetin-containing PEEK/PLGA microparticles.

This study aimed to describe the synthesis and characterization of a calcium phosphate cement (CPC) with polyetheretherketone/poly (lactic-co-glycolic) acid (PEEK/PLGA) micro-particles containing quercetin. CPC powder was synthesized by mixing dicalcium phosphate anhydrate and tetracalcium phosphate. To synthesize PEEK/PLGA microparticles, PLGA85:15 was mixed with 90 wt% PEEK. The weight ratio of quercetin/PLGA/PEEK was 1:9:90 wt%. PEEK/PLGA/quercetin microparticles with 3, 5, and 6 wt% was added to CPC. The setting time, compressive strength, drug release profile, solubility, pH, and porosity of synthesized cement were evaluated. The morphology and physicochemical properties of particles was analyzed by scanning electron microscopy, Fourier-transform infrared spectroscopy (FTIR), x-ray diffraction (XRD), and inductively coupled plasma. Cytotoxicity was assessed by the methyl thiazolyl tetrazolium assay using dental pulp stem cells. Expression of osteoblastic differentiation genes was evaluated by real-time polymerase chain reaction. Data were analyzed by one-way ANOVA and Tukey's test (alpha = 0.05). The setting time of 3 wt% CPC was significantly longer than 5 and 6 wt% CPC (P< 0.001). The 6 wt% CPC had significantly higher compressive strength than other groups (P= 0.001). The release of quercetin from CPCs increased for 5 d, and then reached a plateau. XRD and FTIR confirmed the presence of hydroxyapatite in cement composition. Significantly higher expression of osteocalcin (OCN) and osteopontin (OPN) was noted in 3 wt% and 6 wt% CPCs. Addition of quercetin-containing PEEK/PLGA microparticles to CPC enhanced its compressive strength, decreased its setting time, enabled controlled drug release, and up-regulated OPN and OCN.

An Innovative Drug Delivery System Loaded with a Modified Combination of Triple Antibiotics for Use in Endodontic Applications.

The objective of the current study was to introduce "Polylactic co-Glycolic Acid- (PLGA-) Coated Ceramic Microparticles" as an innovative drug delivery system, loaded with a new combination of triple antibiotics (penicillin G, metronidazole, and ciprofloxacin (PMC)) for use in endodontic treatments. Ceramic microparticles were made from ß-tricalcium phosphate and hydroxyapatite and examined by "Scanning Electronic Microscope (SEM)." Then, fixed amounts of the selected antibiotics were added to a prepared PLGA solution and stirred thoroughly. Next, the prepared ceramic microparticles were dispersed completely in the drugs solution. The deposited "PMC-loaded PLGA-coated ceramic microspheres (PPCMs)" were dried and incubated in phosphate buffer saline (PBS) for 21 days. The drug release from PPCMs was quantified by a UV spectrophotometer. The antimicrobial activity of PPCMs was investigated using the "Agar Plate Diffusion Test (ADT)," "Minimum Inhibitory Concentration (MIC)," and "Minimum Bactericidal Concentration (MBC)" against Enterococcus faecalis (E. faecalis) and Aggregatibacter actinomycetemcomitans (A.a). The cell viability test (MTT) was conducted for cytotoxicity against human gingival fibroblasts. SEM micrographs of PPCMs showed spherical-like ceramic microparticles with smooth surfaces. Crystal-like antibiotic particles (chunks) were also found on PPCMs. Initial burst of antibiotics (31 µg/mL, 160 µg/mL, and 18 µg/mL for ciprofloxacin, metronidazole, and penicillin G, respectively, in the first 4 days) followed by gradual and sustained release was observed within a period of 21 days. PPCMs demonstrated pH close to normal physiological environment and antibacterial activity against E. faecalis and A.a in the first 2 days. MTT showed cell viability of more than 70% for PPCMs after 24 h and 72 h of exposure. In conclusion, PPCMs demonstrated satisfactory release of antibiotics, antibacterial activity against the selected microorganisms, and biocompatibility. Thus, PPCMs may be used to deliver modified triple antibiotics to the root canal system for use in endodontic applications.

Chemical modification of MTA and CEM cement to decrease setting time and improve bioactivity properties by adding alkaline salts.

Background. Mineral trioxide aggregate (MTA) and Calcium-enriched Mixture (CEM) cement are used for pulp capping since they induce the formation of a dentinal bridge. Long setting time is a shortcoming of these types of cement. This study aimed to assess the effect of the incorporation of some alkaline salts to MTA and CEM cement on their setting time, ion release profile, pH, and surface morphology. Methods. In this in vitro experimental study, 5% calcium chloride (CaCl2), calcium oxide (CaO), sodium fluoride (NaF), and calcium nitrate [Ca(NO3)2] were separately added to MTA and CEM cement. The primary and final setting times of the cements were measured using a Gillmore needle apparatus. The samples were immersed in simulated body fluid (SBF) for one, seven, and 14 days and subjected to x-ray diffraction (XRD) and scanning electron microscopy (SEM) for phase identification and surface morphology assessment. The change in the pH of solutions was studied, and the calcium ion release profile was determined using inductively coupled plasma atomic emission spectroscopy (ICP-AES). The data were analyzed with ANOVA, followed by post hoc tests. Results. CaCl2 and CaO decreased the setting time of MTA, and Ca(NO3)2 decreased the setting time of CEM cement. The incorporation of the salts increased the pH and calcium ion release from both cements, and hydroxyapatite deposits were noted to cover the surface of the samples (observed by SEM and confirmed by EDXA). Conclusion. The incorporation of CaCl2 and CaO into MTA and Ca(NO3)2 into CEM cement decreased their setting time and increased their pH and calcium ion release.

Nd:YAG Laser Treatment of Bioglass-coated Zirconia Surface and Its Effect on Bond Strength and Phase Transformation.

PURPOSE: To evaluate the morphological properties, phase transformation, and microshear bond strength of composite cement to bioglass-coated zirconia surfaces treated with Nd:YAG laser. MATERIALS AND METHODS: Seventy-five zirconia disks were divided into five groups (n = 15). Group C received no surface treatment (control). Group S was subjected to sandblasting with 50-µm aluminum oxide particles. Group B samples were coated with bioglass 45S5. Groups BL9 and BL5 received bioglass coating and laser irradiation with 9 J/cm2 and 5 J/cm2 energy density. Morphological assessment was done using atomic force microscopy (AFM) and scanning electron microscopy (SEM). Zirconia phase transformation was assessed by XRD. Microhear bond strength testing was performed using a modified microtensile tester. The data were analyzed using the Welch test and the Games-Howell test (p < 0.05). RESULTS: The sandblasted and bioglass-coated groups showed the highest bond strengths compared to other groups (p < 0.05). Group S showed the highest surface roughness and the highest frequency of cohesive failure. In all samples, the tetragonal phase decreased after surface treatment. Groups BL9 and BL5 showed some levels of tetragonal to cubic phase transformation. CONCLUSION: Bioglass coating of zirconia surfaces (using the slurry method) can increase its microshear bond strength comparable to that of sandblasting. Surface roughness of sandblasted zirconia was the highest among all methods. Irradiation of Nd:YAG laser on bioglass-coated zirconia surfaces is not effective and decreases its bond strength compared to sandblasting and bioglass coating. Increasing the Nd:YAG laser energy density cannot increase the surface roughness of bioglass-coated zirconia surfaces. Bioglass coating results in transformation of the tetragonal to the cubic phase.

Triple antibiotic paste: momentous roles and applications in endodontics: a review.

This study investigated the latest findings and notions regarding 'triple antibiotic paste' (TAP) and its applications in dentistry, particularly endodontics. TAP is a combination of 3 antibiotics, ciprofloxacin, metronidazole, and minocycline. Despite the problems and pitfalls research pertaining to this paste has unveiled, it has been vastly used in endodontic treatments. The paste's applications vary, from vital pulp therapy to the recently introduced regeneration and revascularisation protocol. Studies have shown that the paste can eliminate the root canal microorganisms and prepare an appropriate matrix for further treatments. This combination is able to remove diverse groups of obligate and facultative gram-positive and gram-negative bacteria, providing an environment for healing. In regeneration protocol cases, this allows the development, disinfection, and possible sterilization of the root canal system, so that new tissue can infiltrate and grow into the radicular area. Moreover, TAP is capable of creating a discipline in which other wanted and needed treatments can be successfully performed. In conclusion, TAP, as an antibacterial intracanal medication, has diverse uses. Nevertheless, despite its positive effects, the paste has shown drawbacks. Further research concerning the combined paste and other intracanal medications to control microbiota is a must.

Effects of pore orientation on in-vitro properties of retinoic acid-loaded PLGA/gelatin scaffolds for artificial peripheral nerve application.

Different manufacturing processes of scaffolds affect their main properties by altering the microstructure of pores. In this study, poly (lactic-co-glycolic acid) (PLGA) scaffolds were synthesized by both freeze casting and freeze drying methods. Scanning electron microscopy (SEM) micrographs demonstrated a unidirectional microstructure in the freeze-cast and a number of random pores in the freeze-dried scaffolds. According to the results, the formation of a lamellar microstructure increased the mechanical strength, swelling ratio, biodegradation behavior and drug release level. Addition of gelatin to the PLGA freeze-cast constructs led to an increase in the average diameter of pores, hydrophilicity and cellular spreading. The gelatin-containing scaffolds showed a decreased mechanical strength, but at the same time, an enhanced swelling ratio, biodegradation rate and drug release level. Differentiation of P19 cells and expression of ß-tubulin III, Pax-6 and Nestin were improved by incorporating retinoic acid in PLGA-Gelatin freeze-cast scaffolds. This is a good option with initial necessary features for regenerating peripheral nervous system (PNS).

Ultraviolet-induced surface grafting of octafluoropentyl methacrylate on polyether ether ketone for inducing antibiofilm properties.

Since octafluoropentyl methacrylate is an antifouling polymer, surface modification of polyether ether ketone with octafluoropentyl methacrylate is a practical approach to obtaining anti-biofilm biocompatible devices. In the current study, the surface treatment of polyether ether ketone by the use of ultraviolet irradiation, so as to graft (octafluoropentyl methacrylate) polymer chains, was initially implemented and then investigated. The Fourier-transform infrared and nuclear magnetic resonance spectra corroborated the appearance of new signals associated with the fluoroacrylate group. Thermogravimetric curves indicated enhanced asymmetry in the polymer structure due to the introduction of the said new groups. Measuring the peak area in differential scanning calorimetry experiments also showed additional bond formation. Static water contact angle measurements indicated a change in wettability to the more hydrophobic surface. The polyether ether ketone-octafluoropentyl methacrylate surface greatly reduced the protein adsorption. This efficient method can modulate and tune the surface properties of polyether ether ketone according to specific applications.

In vitro behavior of poly-lactic-co-glycolic acid microspheres containing minocycline, metronidazole, and ciprofloxacin.

AIM: In the present study, we aimed to fabricate poly-lactic-co-glycolic acid (PLGA) microspheres containing a mixture of three antibiotics-minocycline, metronidazole, and ciprofloxacin (MMC)-to assess their efficacy and properties. METHODS: MMC were loaded onto PLGA biopolymer microspheres at a 1:1:1 ratio using the double emulsion technique. The morphology of microspheres was observed by a (SEM). The controlled release of antibiotics was evaluated over an 18-day period. The antibacterial efficacy of released antibiotics against Aggregatibacter actinomycetemcomitans was evaluated by measuring the diameter of the growth-inhibition zone. The cytotoxicity of MMC-containing microspheres was also evaluated and compared using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. One-way anova was used for the data analysis. RESULTS: SEM micrographs confirmed the spherical shape and smooth surface of microspheres. The adequate release of antibiotics was observed from the microspheres within the desired time period of 16-18 days. The MMC-containing microspheres showed antibacterial activity for 11 days. Moreover, MMC-containing microspheres showed superior cell biocompatibility compared to the free mixture of the three antibiotics (P < 0.05). CONCLUSION: Microspheres containing triple antibiotics showed good release, antibacterial activity for 11 days, and similar cell biocompatibility compared to the empty microspheres.

Physicochemical and mechanical properties of freeze cast hydroxyapatite-gelatin scaffolds with dexamethasone loaded PLGA microspheres for hard tissue engineering applications.

Hydroxyapatite (HA)-gelatin scaffolds incorporated with dexamethasone-loaded polylactic-co-glycolic acid (PLGA) microspheres were synthesized by freeze casting technique. Scanning electron microscopy (SEM) micrographs demonstrated a unidirectional microstructure and a decrease in the pore size as a function of temperature gradient. Higher amounts of HA resulted in a decrease in the pore size. According to the results, at lower cooling rates, the formation of a lamellar structure decreased the mechanical strength, but at the same time, enhanced the swelling ratio, biodegradation rate and drug release level. On the other hand, higher weight ratios of HA increased the compressive strength, and reduced the swelling ratio, biodegradation rate and drug release level. The results obtained by furrier transform infrared spectroscopy (FTIR) and bioactivity analysis illustrated that the interactions of the materials support the apatite formation in the simulated body fluid (SBF) solution. Based on the obtained results, the synthesized composite scaffolds have the necessary mechanical and physicochemical features to support the regeneration of defects and to maintain their stability during the neo-tissue formation.

Adipose-derived stem cells combined with beta-tricalcium phosphate: a novel possible strategy for periodontal defects regeneration.

Regeneration of destroyed periodontal tissue is a complicated problem in periodontal therapy. Conventional strategies such as surgical techniques, occlusive barrier membranes, and bone grafts have disadvantages that limit their application. Tissue engineering is a novel approach to regenerate periodontal tissue overcoming limitations of current strategies. In recent studies, researchers reported the potential of adipose-derived stem cells (ADSCs) to use in periodontal tissue regeneration. Unfortunately, in vivo studies indicated that small amount of alveolar bone formed using ADSCs implantation in the periodontal defects, which would be overcome by inducing osteogenic differentiation of ADSCs using osteoinductive biomaterials combined with ADSCs. Beta-tricalcium phosphate (beta-TCP) is an osteoinductive material which reported to induce osteogenic differentiation of adipose-derived stem cells. Based on the performed studies, we hypothesize that ADSCs from Wistar rat are isolated, induced by appropriate signaling molecules, seeded by beta-TCP, and then the complex was implanted into the periodontal defects in the same Wistar rat to observe the regeneration of periodontal tissue in vivo. This study will explore the possibility and application of ADSCs/beta-TCP complex for reconstructing periodontal defects. We believe it is especially useful to future clinical study and application in this field.

Effect of poly-L-lysine coating on retinoic acid-loaded PLGA microspheres in the differentiation of carcinoma stem cells into neural cells.

In this study, PLGA microspheres were prepared using a water-in-oil-in-water emulsion/solvent evaporation technique. Some microspheres were coated with poly-L-lysine (an extracellular matrix (ECM) component), and then pluripotent P19 embryonic carcinoma cells were seeded on them. P19 cells attached onto the PLGA microspheres; subsequently, by adding retinoic acid (RA) to cell culture medium as a neurogenic inducer (RA was released from the microspheres), the cells differentiated into neural cells. Size and morphology of PLGA microspheres was characterized by scanning electron microscopy (SEM). Neurogenic differentiation was studied by immunofluorescent staining, real-time polymerase chain reaction (RT-PCR), and light microscopy. Histological assay showed that more cells attached onto microspheres coated with poly-L-lysine than the uncoated group. Immunofluoresent staining and RT-PCR analysis for ß-Tubulin, Nestin and Pax6 genes indicated differentiation of P19 cells into neural cells on both coated and uncoated microspheres. It was found that a high surface area of microspheres improves cell attachment and expansion, which was significantly increased in those coated with poly-L-lysine. Finally, these results highlight the versatility of these sample scaffolds as a model system for nerve tissue engineering.

Preparation and surface characterization of poly-L-lysine-coated PLGA microsphere scaffolds containing retinoic acid for nerve tissue engineering: in vitro study.

The pluripotent nature and proliferative capacity of embryonic stem cells make them an attractive cell source for tissue engineering. In this study, the poly-L-lysine-coated PLGA microspheres which contain retinoic acid (RA) as an inducer factor were prepared by using a water-in-oil-in-water emulsion/solvent evaporation technique. Then, pluripotent P19 embryonic carcinoma cells were seeded on them for differentiating into neural cells. Size and surface morphology of PLGA microspheres were evaluated by scanning electron microscope (SEM). For in vitro examinations, SEM, MTT assay, immunofluorescent staining, histology and reverse transcriptase-polymerase chain reaction (RT-PCR) analyses were carried out. SEM micrographs of the scaffolds showed a diameter in range of 13-100 microm. Based on the release profiles obtained, the concentration of RA released from microspheres reached 10(-6) to 10(-7) mg/ml. MTT assay showed that the number of cells attached on coated microspheres were more in comparison with uncoated microspheres. Immunoflourescent staining and RT-PCR analyses for MapII, beta-tubulin III, Nestin and Pax6 indicated differentiation of P19 cells into neural cells on all of the samples. Finally, the counting of positive cells showed 80+/-8.8% and 72+/-6.9% of the cells expressed beta-tubulin III on the surface of coated and uncoated RA-loaded PLGA microspheres, respectively, while the 64+/-1.1% (P < 0.05) cells expressed tubulin III in group with soluble.