Enhanced osteoinductive capacity of poly(lactic-co-glycolic) acid and biphasic ceramic scaffolds by embedding simvastatin.

OBJECTIVES: This study evaluated the effect of embedding simvastatin (SIM) on the osteoinductive capacity of PLGA + HA/ßTCP scaffolds in stem cells from human exfoliated deciduous teeth (SHED). MATERIALS AND METHODS: Scaffolds were produced by PLGA solvent dissolution, addition of HA/ßTCP, solvent evaporation, and leaching of sucrose particles to impart porosity. Biphasic ceramic particles (70% HA/30% ßTCP) were added to the PLGA in a 1:1 (w:w) ratio. Scaffolds with SIM received 1% (w:w) of this medication. Scaffolds were synthesized in a disc-shape and sterilized by ethylene oxide. The experimental groups were (G1) PLGA + HA/ßTCP and (G2) PLGA + HA/ßTCP + SIM in non-osteogenic culture medium, while (G3) SHED and (G4) MC3T3-E1 in osteogenic culture medium were the positive control groups. The release profile of SIM from scaffolds was evaluated. DNA quantification assay, alkaline phosphatase activity, osteocalcin and osteonectin proteins, extracellular calcium detection, von Kossa staining, and X-ray microtomography were performed to assess the capacity of scaffolds to induce the osteogenic differentiation of SHED. RESULTS: The release profile of SIM followed a non-liner sustained-release rate, reaching about 40% of drug release at day 28. Additionally, G2 promoted the highest osteogenic differentiation of SHED, even when compared to the positive control groups. CONCLUSIONS: In summary, the osteoinductive capacity of poly(lactic-co-glycolic) acid and biphasic ceramic scaffolds was expressively enhanced by embedding simvastatin. CLINICAL RELEVANCE: Bone regeneration is still a limiting factor in the success of several approaches to oral and maxillofacial surgeries, though tissue engineering using mesenchymal stem cells, scaffolds, and osteoinductive mediators might collaborate to this topic.

Release of simvastatin from scaffolds of poly(lactic-co-glycolic) acid and biphasic ceramic designed for bone tissue regeneration.

The aim of this study was to evaluate the release of simvastatin from scaffolds composed of poly(lactic-co-glycolic) acid (PLGA) and biphasic ceramic designed for bone engineering and to assess the physico-chemical and mechanical properties of the scaffolds. Samples with 30% and 70% porosity were obtained with 0, 2, 5, and 8 wt %. of simvastatin through the solvent evaporation technique and leaching of sucrose particles. Scaffold degradation and simvastatin release were evaluated in phosphate-buffered saline. Scaffolds were analyzed by scanning electron microscopy and microtomography for two-dimensional and three-dimensional morphological characterization of the porosity, connectivity, and intrinsic permeability. The mechanical characterization was conducted based on the compressive strength and the chemical characterization by differential scanning calorimetry and energy dispersive X-ray spectroscopy. Gradual and prolonged simvastatin release from the scaffolds was observed. The release followed the Korsmeyer kinetics model with the predominance of case II transport for 30% porosity scaffolds, and anomalous behavior for the 70% porosity samples. Simvastatin release was also influenced by the slow scaffold degradation due to the strong chemical interaction between simvastatin and PLGA, as observed by differential scanning calorimetry. The scaffolds presented spherical and sucrose crystal-shaped pores that resulted in a homogenous porosity, with a predominance of open pores, ensuring interconnectivity. Simvastatin incorporation into the scaffolds and increased porosity did not influence the mechanical properties. The scaffolds presented gradual and prolonged simvastatin release, with satisfactory physico-chemical and mechanical properties. The scaffolds presented gradual and prolonged simvastatin release, with satisfactory physico-chemical and mechanical properties, a promise for applications in bone regeneration. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2152-2164, 2019.

Effects of manual threshold setting on image analysis results of a sandstone sample structural characterization by X-ray microtomography.

Binarization process plays an important role in structural characterization by means of micro-CT images analysis. The choice of the correct threshold to separate porous phase from the material is the procedure for binary images creation. Slight variations of the threshold level led to substantial variations in physical parameters determination. The aim of this work is to evaluate these variations based on manual threshold settings data of five operators. Porosity and pore size distribution of a sandstone sample were determined.