Enhanced bone tissue regeneration with hydrogel-based scaffolds by embedding parathyroid hormone in mesoporous bioactive glass.

OBJECTIVES: To evaluate hydrogel-based scaffolds embedded with parathyroid hormone (PTH)-loaded mesoporous bioactive glass (MBG) on the enhancement of bone tissue regeneration in vitro. MATERIALS AND METHODS: MBG was produced via sol-gel technique followed by PTH solution imbibition. PTH-loaded MBG was blended into the hydrogels and submitted to a lyophilisation process associated with a chemical crosslinking reaction to the production of the scaffolds. Characterisation of the MBG and PTH-loaded MBG scaffolds, including the scanning electron microscope (SEM) connected with an X-ray detector (EDX), Fourier transform infrared (FTIR), compression strength, rheological measurements, swelling and degradation rates, and PTH release analysis, were performed. Also, bioactivity using simulated-body fluid (SBF), biocompatibility (MTT), and osteogenic differentiation analyses (von Kossa and Alizarin Red stainings, and µ-computed tomography, µCT) of the scaffolds were carried out. RESULTS: SEM images demonstrated MBG particles dispersed into the hydrogel-based scaffold structure, which was homogeneously porous and well interconnected. EDX and FTIR revealed large amounts of carbon, oxygen, sodium, and silica in the scaffold composition. Bioactivity experiments revealed changes on sample surfaces over the analysed period, indicating the formation of carbonated hydroxyapatite; however, the chemical composition remained stable. PTH-loaded hydrogel-based scaffolds were biocompatible for stem cells from human-exfoliated deciduous teeth (SHED). A high quantity of calcium deposits on the extracellular matrix of SHED was found for PTH-loaded hydrogel-based scaffolds. µCT images showed MBG particles dispersed into the scaffolds' structure, and a porous, lamellar, and interconnected hydrogel architecture. CONCLUSIONS: PTH-loaded hydrogel-based scaffolds demonstrated consistent morphology and physicochemical properties for bone tissue regeneration, as well as bioactivity, biocompatibility, and osteoinductivity in vitro. Thus, the scaffolds presented here are recommended for future studies on 3D printing. CLINICAL RELEVANCE: Bone tissue regeneration is still a challenge for several approaches to oral and maxillofacial surgeries, though tissue engineering applying SHED, scaffolds, and osteoinductive mediators might help to overcome this clinical issue.

PLGA+HA/ßTCP Scaffold Incorporating Simvastatin: A Promising Biomaterial for Bone Tissue Engineering.

The aim of this study was to synthesize, characterize, and evaluate degradation and biocompatibility of poly(lactic-co-glycolic acid) + hydroxyapatite/ß-tricalcium phosphate (PLGA+HA/ßTCP) scaffolds incorporating simvastatin (SIM) to verify if this biomaterial might be promising for bone tissue engineering. Samples were obtained by the solvent evaporation technique. Biphasic ceramic particles (70% HA, 30% ßTCP) were added to PLGA in a ratio of 1:1. Samples with SIM received 1% (m/m) of this medication. Scaffolds were synthesized in a cylindric shape and sterilized by ethylene oxide. For degradation analysis, samples were immersed in phosphate-buffered saline at 37°C under constant stirring for 7, 14, 21, and 28 days. Nondegraded samples were taken as reference. Mass variation, scanning electron microscopy, porosity analysis, Fourier transform infrared spectroscopy, differential scanning calorimetry, and thermogravimetry were performed to evaluate physico-chemical properties. Wettability and cytotoxicity tests were conducted to evaluate the biocompatibility. Microscopic images revealed the presence of macro-, meso-, and micropores in the polymer structure with HA/ßTCP particles homogeneously dispersed. Chemical and thermal analyses presented similar results for both PLGA+HA/ßTCP and PLGA+HA/ßTCP+SIM. The incorporation of simvastatin improved the hydrophilicity of scaffolds. Additionally, PLGA+HA/ßTCP and PLGA+HA/ßTCP+SIM scaffolds were biocompatible for osteoblasts and mesenchymal stem cells. In summary, PLGA+HA/ßTCP scaffolds incorporating simvastatin presented adequate structural, chemical, thermal, and biological properties for bone tissue engineering.

Virucidal activity of microalgae extracts harvested during phycoremediation of swine wastewater.

Phycoremediation of swine wastewater is a promising treatment since it efficiently removes nutrients and contaminants and, simultaneously, its biomass can be harvested and used to obtain a wide range of valuable compounds and metabolites. In this context, biomass microalgae were investigated for the phycoremediation of swine wastewater, and biomass extracts for its virucidal effect against enveloped and non-enveloped viruses. Microalgae were cultivated in a pilot scale bioreactor fed with swine wastewater as the growth substrate. Hexane, dichloromethane, and methanol were used to obtain the microalgae extracts. Extracts were tested for virucidal potential against HSV-1 and HAdV-5. Virucidal assays were conducted at temperatures that emulate environmental conditions (21 °C) and body temperature (37 °C). The maximum production of microalgae biomass reached a concentration of 318.5 ± 23.6 mgDW L-1. The results showed that phycoremediation removed 100% of ammonia-N and phosphate-P, with rates (k1) of 0.218 ± 0.013 and 0.501 ± 0.038 (day-1), respectively. All microalgae extract reduced 100% of the infectious capacity of HSV-1. The microalgae extracts with dichloromethane and methanol showed inhibition activities at the lowest concentration (3.125 µg mL-1). Virucidal assays against HAdV-5 using microalgae extract of hexane and methanol inhibited the infectious capacity of the virus by 70% at all concentrations tested at 37 °C. At a concentration of 12.5 µg mL-1, the dichloromethane microalgae extract reduced 50-80% of the infectious capacity of HAdV-5, also at 37 °C. Overall, the results suggest that the microalgae can be an attractive source of feedstock biomass for the exploration of alternative virucidal compounds.

Bioactive Compounds from Mangrove Endophytic Fungus and Their Uses for Microorganism Control.

Mangroves are ecosystems with unique characteristics due to the high salinity and amount of organic matter that house a rich biodiversity. Fungi have aroused much interest as they are an important natural source for the discovery of new bioactive compounds, with potential biotechnological and pharmacological interest. This review aims to highlight endophytic fungi isolated from mangrove plant species and the isolated bioactive compounds and their bioactivity against protozoa, bacteria and pathogenic viruses. Knowledge about this type of ecosystem is of great relevance for its preservation and as a source of new molecules for the control of pathogens that may be of importance for human, animal and environmental health.

Number of dental abutments influencing the biomechanical behavior of tooth‒implant-supported fixed partial dentures: A finite element analysis.

Background. Local or systemic issues might prevent installing a sufficient number of dental implants for fixed prosthetic rehabilitation. Splinting dental implants and natural teeth in fixed dentures could overcome such limitations. Therefore, this study aimed to evaluate the influence of the number of dental abutments in the biomechanics of tooth‒implant-supported fixed partial dentures (FPDs). The null hypothesis was that increasing the number of abutment teeth would not decrease the stress over the abutments and surrounding bone. Methods. Left mandibular lateral incisor, canine, premolars, and molars were reconstructed through computed tomography and edited using image processing software to represent a cemented fixed metal‒ceramic partial denture. Three models were set to reduce the number of abutment teeth: 1) lateral incisor, canine, and first premolar; 2) canine and first premolar; 3) the first premolar. The second premolar and first molar were set as pontics, and the second molar was set as an implant abutment in all the models. Finite element analyses were performed under physiologic masticatory forces with axial and oblique loading vectors. Results. After simulation of axial loads, the stress peaks on the bone around the implant, the bone around the first premolar, and prosthetic structures did not exhibit significant changes when the number of abutment teeth decreased. However, under oblique loads, decreasing the number of abutment teeth increased stress peaks on the surrounding bone and denture. Conclusion. Increasing the number of dental abutments in tooth‒implant-supported cemented FPD models decreased stresses on its constituents, favoring the prosthetic biomechanics.

Physico-chemical characterization and biocompatibility evaluation of hydroxyapatites.

The aim of this study was to evaluate the physico-chemical and biocompatibility characteristics of two different hydroxyapatites. Physical and chemical properties were analyzed using granulometric analysis, scanning electron microscopy (SEM), X-ray energy-dispersion (EDX), X-ray fuorescence (XRF) and X-ray diffraction (XRD). Biomaterials were implanted into the subcutaneous tissue on the dorsum of 36 Wistar rats, divided into the following groups: Group 1 - Gen-Ox (natural); Group 2 - HA-U (synthetic) and Group 3 - Control (Sham). After 15 and 30 days, 6 animals/period were sacrificed and the subcutaneous tissue was taken for histological and histometric analysis, giving consideration to inflammatory reaction and granule area. The granulometric test results showed a mean granule diameter of 161.6 microm (min = 19.0 microm; max = 498.0 microm) and 48.7 microm (min = 7.0 microm; max = 256.0 microm) for groups 1 and 2 respectively. Analysis with SEM demonstrated irregular and sharp-edge particles in group 1 (3332.8 +/- 274.3 microm(2)) and irregular and rounded particles in group 2 (1320.8 +/- 83.0 microm(2)) (P < 0.0001; Student's t test). EDX and XRF revealed calcium, carbon, oxygen, sodium and phosphorus in both groups. XRD indicated that both biomaterials were pure and crystalline. There was a statistically significant difference in granule area between the two groups after 15 days (P = 0.022; Student's t-test). After 15 days, an increased inflammatory response was seen in group 2 (P < 0.0001; ANOVA and Tukey's post hoc test) whereas it was more pronounced in group 1 after 30 days (P < 0.0001; ANOVA and Tukey's post hoc test). It was concluded that these biomaterials have similar physical, chemical and biocompatibility characteristics.

Development and physicochemical characterization of saquinavir mesylate solid dispersions using Gelucire 44/14 or PEG 4000 as carrier.

Solid dispersions of saquinavir mesylate containing either Gelucire® 44/14 or poly(ethylene glycol) (PEG) 4000, or mixtures of each carrier with Tween 80 or polyvinyl pyrrolidone (PVP) K30 were prepared in order to enhance the drug dissolution rate. These systems were prepared by the melting method and characterized by X-ray powder diffraction, microscopical techniques, and Raman spectroscopy aiming to establish a relationship between physicochemical and dissolution properties under different cooling conditions. Modifications in degree of crystalline order/disorder over time were observed in preparations with both carriers. Overall, formulations cooled and stored at -20 °C showed less variation in dissolution rates than those at 25 °C. Although Tween 80 has enhanced the known self-emulsifying properties of Gelucire® 44/14, its combination with PEG 4000 displayed miscibility problems. The addition of PVP K30 was not the most effective approach in enhancing the dissolution in early steps; however, the drug dissolution was stable after 7 days of storage at 25 °C. The combination of PEG 4000 and PVP K30 maintained the dissolution properties for 60 and 90 days at 25 °C/95% relative humidity and 40 °C/75% (f2 values >50), respectively.

Evaluation of physical-chemical properties and biocompatibility of a microrough and smooth bioactive glass particles.

The purpose of this study was to evaluate physical-chemical and biocompatibility characteristics of a simple synthesis and low cost experimental bioactive glass. Physical and chemical properties were analyzed using scanning electron microscopy (SEM), X-ray energy dispersive (EDX), X-ray fluorescence (XRF) and X-ray diffraction (XRD). The biomaterials were subcutaneously implanted into rats, according to the following groups: G1, PerioGlastrade mark; G2, Biograntrade mark, G3, Experimental Bioactive Glass U (BGU) and G4, Control (Sham). After 7, 15, 21, 45, and 60 days, 5 animals/group/period were sacrificed and the subcutaneous tissue was dissected for histological and histometric analysis, considering inflammatory reaction and granulation area, presence of polymorphonuclear (PMN), monuclear (MN) and fibroblast (F) cells. SEM analysis of biomaterials showed irregular particles with different surface characteristics. EDX showed calcium, oxygen, sodium, phosphorus and silicon; XRF revealed silica oxide (SiO(2)), sodium oxide (Na(2)O), calcium oxide (CaO) and phosphorus oxide (P(2)O(5)). XRD indicated non crystalline phase. Measurement of tissue reaction showed similar results among the experimental groups at 45 and 60 days. No difference was found for PMN, MN and F cell counts. All biomaterials exhibited partial resorption. In conclusion, the experimental bioactive glass analyzed showed physical and chemical characteristics similar to the commercially available biomaterials, and was considered biocompatible, being partially reabsorbed in the subcutaneous tissue.