ABSTRACT
Nanostructured porous silicon (pSi) is a synthetic silicon-based material. Its biocompatibility and bioresorbability in body fluids make pSi an appealing biomaterial for tissue engineering, with surfaces characteristics facilitating human cell adhesion and differentiation. The resorption kinetics of such porous biomaterials is crucial for in vivo bone regeneration, in order to adapt biomaterial resorption to tissue formation, and to control the release of loaded bioactive molecules. We investigated pSi as a bioactive scaffold for bone tissue engineering, with an emphasis on kinetics of pSi resorption and silicon release. PSi particles and chips were fabricated from crystalline silicon, and functionalized by oxidation and chemical grafting of amine groups to mimic biological structures. Materials resorption over time was investigated with Raman spectroscopy, infrared spectroscopy, and Scanning Electron Microscopy. Silicon release was followed by mass spectrometry. Particle degradation and inclusion in newly formed bone were studied in vivo. The in vitro experiments revealed that non-oxidized pSi had an accelerated initial dissolution in ddH2O and an inhibition of initial Si release in SBF. This high reactivity also led to transformation towards amorphous non-resorbable silica when incubated in SBF. PSi resorption started immediately with a maximal dissolution in the first 24 h. Later, the dissolution rate decreased over time. In comparison, the resorption process of oxidized pSi seemed delayed, but more continuous. This delayed dissolution increased the bioactivity and stability, leading to enhanced bone formation in vivo. Delayed pSi degradation provided a constant surge of silicic acid over time and promoted bone regeneration, demonstrating the high potential of pSi for bone tissue engineering: Oxidized pSi were almost completely resorbed after 2 months of healing, with remaining partially dissolved particles surrounded by newly formed bone. On the contrary, non-oxidized particles were still obviously present after 2 months with limited bone regeneration. This delayed resorption is consistent with the in vitro observations in SBF, and particles' transformation towards silica.
ABSTRACT
Dental caries, a preventable disease, is caused by highly-adherent, acid-producing biofilms composed of bacteria and yeasts. Current caries-preventive approaches are ineffective in controlling biofilm development. Recent studies demonstrate definite advantages in using natural compounds such as trans-cinnamaldehyde in thwarting biofilm assembly, and yet, the remarkable difficulty in delivering such hydrophobic bioactive molecules prevents further development. To address this critical challenge, we have developed an innovative platform composed of components with a proven track record of safety. We fabricated and thoroughly characterised porous silicon (pSi) microparticles to carry and deliver the natural phenyl propanoid trans-cinnamaldehyde (TC). We investigated its effects on preventing the development of cross-kingdom biofilms (Streptococcus mutans and Candida albicans), typical of dental caries found in children. The prepared pSi microparticles were roughly cubic in structure with 70-75% porosity, to which the TC (pSi-TC) was loaded with about 45% efficiency. The pSi-TC particles exhibited a controlled release of the cargo over a 14-day period. Notably, pSi-TC significantly inhibited biofilms, specifically downregulating the glucan synthesis pathways, leading to reduced adhesion to the substrate. Acid production, a vital virulent trait for caries development, was also hindered by pSi-TC. This pioneering study highlights the potential to develop the novel pSi-TC as a dental caries-preventive material.
ABSTRACT
Titanium dental implants are used routinely, with surgical procedure, to replace missing teeth. Even though they lead to satisfactory results, novel developments with implant materials can still improve implant treatment outcomes. The aim of this study was to investigate the efficiency of porous tantalum (Ta) dental implants for osseointegration, in comparison to classical titanium (Ti). Mesenchymal stem cells from the dental pulp (DPSC) were incubated on Ta, smooth titanium (STi), and rough titanium (RTi) to assess their adhesion, proliferation, osteodifferentiation, and mineralized matrix production. Cell proliferation was measured at 4 h, 24 h, 48 h with MTT test. Early osteogenic differentiation was followed after 4, 8, 12 days by alkaline phosphatase (ALP) quantification. Cells organization and matrix microstructure were studied with scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX). Collagen production and matrix mineralization were evaluated by immunostaining and histological staining. MTT test showed significantly higher proliferation of DPSC on Ta at 24 h and 48 h. However, APL quantification after 8 and 12 days was significantly lower for Ta, revealing a delayed differentiation, where cells were proliferating the more. After 3 weeks, collagen immunostaining showed an efficient production of collagen on all samples. However, Red Alizarin staining clearly revealed a higher calcification on Ta. The overall results tend to demonstrate that DPSC differentiation is delayed on Ta surface, due to a longer proliferation period until cells cover the 3D porous Ta structure. However, after 3 weeks, a more abundant mineralized matrix is produced on and inside Ta implants. Cell populations on porous Ta proliferate greater and faster, leading to the production of more calcium phosphate deposits than cells on roughened and smooth titanium surfaces, revealing a potential enhanced capacity for osseointegration.
ABSTRACT
Clonal analysis of patients with triple negative myeloproliferative neoplasm (MPN) has provided evidence of additional aberrations, including epigenetic alterations. To discover such novel genetic aberrations, patients were screened through next-generation sequencing using a myeloid sequencing panel of 54 genes using a genetic analyser. Genetic variants in 28 genes, including TET2, BCOR, BCR, and ABL1 were identified in a triple negative essential thrombocythemia (ET) patient. The individual role of some of these variants in disease pathogenesis has yet to be studied. Somatic mutations in the same genes have been reported with variable frequencies in myeloid malignancies. However, no pathogenic impact of these variants could be found; therefore, long-term follow up of patients with genetic analysis of a large cohort and the use of whole genome sequencing is required to assess the effects of these variants.