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Resin-based dental restorative materials are extensively used today in dentistry. However, significant concerns still remain regarding their biocompatibility. For this reason, significant scientific effort has been focused on the determination of the molecular toxicology of substances released by these biomaterials, using several tools for risk assessment, including exposure assessment, hazard identification and dose-response analysis. These studies have shown that substances released by these materials can cause significant cytotoxic and genotoxic effects, leading to irreversible disturbance of basic cellular functions. The aim of this article is to review current knowledge related to dental composites’ molecular toxicology and to give implications for possible improvements concerning their biocompatibility.

Titanium implants are widely used in the orthopedic and dentistry fields for many decades, for joint arthroplasties, spinal and maxillofacial reconstructions, and dental prostheses. However, despite the quite satisfactory survival rates failures still exist. New Ti-alloys and surface treatments have been developed, in an attempt to overcome those failures. This review provides information about new Ti-alloys that provide better mechanical properties to the implants, such as superelasticity, mechanical strength, and corrosion resistance. Furthermore, in vitro and in vivo studies, which investigate the biocompatibility and cytotoxicity of these new biomaterials, are introduced. In addition, data regarding the bioactivity of new surface treatments and surface topographies on Ti-implants is provided. The aim of this paper is to discuss the current trends, advantages, and disadvantages of new titanium-based biomaterials, fabricated to enhance the quality of life of many patients around the world.

Stem cells from the apical papilla (SCAP) of human adult teeth are considered an accessible source of cells with angiogenic properties. The aims of this study were to investigate the endothelial transdifferentiation of SCAP, the secretion of pro-and antiangiogenic factors from SCAP, and the paracrine effects of SCAP when exposed to environmental stress to stimulate tissue damage. SCAP were exposed to serum deprivation (SD), glucose deprivation (GD), and oxygen deprivation/hypoxia (OD) conditions, individually or in combination. Endothelial transdifferentiation was evaluated by in vitro capillary-like formation assays, real-time polymerase chain reaction, western blot, and flow cytometric analyses of angiogenesis-related markers; secretome by antibody arrays and enzyme-linked immunosorbent assays (ELISA); and paracrine impact on human umbilical vein endothelial cells (HUVECs) by in vitro transwell migration and capillary-like formation assays. The short-term exposure of SCAP to glucose/oxygen deprivation (GOD) in the presence, but mainly in deprivation, of serum (SGOD) elicited a proangiogenesis effect indicated by expression of angiogenesis-related genes involved in vascular endothelial growth factor (VEGF)/VEGFR and angiopoietins/Tie pathways. This effect was unachievable under SD in normoxia, suggesting that the critical microenvironmental condition inducing rapid endothelial shift of SCAP is the combination of SGOD. Interestingly, SCAP showed high adaptability to these adverse conditions, retaining cell viability and acquiring a capillary-forming phenotype. SCAP secreted higher numbers and amounts of pro-(angiogenin, IGFBP-3, VEGF) and lower amounts of antiangiogenic factors (serpin-E1, TIMP-1, TSP-1) under SGOD compared with SOD or SD alone. Finally, secretome obtained under SGOD was most effective in inducing migration and capillary-like formation by HUVECs. These data provide new evidence on the microenvironmental factors favoring endothelial transdifferentiation of SCAP, uncovering the molecular mechanisms regulating their fate. They also validate the angiogenic properties of their secretome giving insights into preconditioning strategies enhancing their therapeutic potential.

BackgroundDevelopment of clinical-grade cell preparations is central to meeting the regulatory requirements for cellular therapies under good manufacturing practice-compliant (cGMP) conditions. Since addition of animal serum in culture media may compromise safe and efficient expansion of mesenchymal stem cells (MSCs) for clinical use, this study aimed to investigate the potential of two serum/xeno-free, cGMP culture systems to maintain long-term “stemness” of oral MSCs (dental pulp stem cells (DPSCs) and alveolar bone marrow MSCs (aBMMSCs)), compared to conventional serum-based expansion.MethodsDPSC and aBMMSC cultures (n = 6/cell type) were established from pulp and alveolar osseous biopsies respectively. Three culture systems were used: StemPro_MSC/SFM_XenoFree (Life Technologies); StemMacs_MSC/XF (Miltenyi Biotek); and α-MEM (Life Technologies) with 15% fetal bovine serum. Growth (population doublings (PDs)), immunophenotypic (flow cytometric analysis of MSC markers) and senescence (β-galactosidase (SA-β-gal) activity; telomere length) characteristics were determined during prolonged expansion. Gene expression patterns of osteogenic (ALP, BMP-2), adipogenic (LPL, PPAR-γ) and chondrogenic (ACAN, SOX-9) markers and maintenance of multilineage differentiation potential were determined by real-time PCR.ResultsSimilar isolation efficiency and stable growth dynamics up to passage 10 were observed for DPSCs under all expansion conditions. aBMMSCs showed lower cumulative PDs compared to DPSCs, and when StemMacs was used substantial delays in cell proliferation were noted after passages 6–7. Serum/xeno-free expansion produced cultures with homogeneous spindle-shaped phenotypes, while serum-based expansion preserved differential heterogeneous characteristics of each MSC population. Prolonged expansion of both MSC types but in particular the serum/xeno-free-expanded aBMMSCs was associated with downregulation of CD146, CD105, Stro-1, SSEA-1 and SSEA-4, but not CD90, CD73 and CD49f, in parallel with an increase of SA-gal-positive cells, cell size and granularity and a decrease in telomere length. Expansion under both serum-free systems resulted in “osteogenic pre-disposition”, evidenced by upregulation of osteogenic markers and elimination of chondrogenic and adipogenic markers, while serum-based expansion produced only minor changes. DPSCs retained a diminishing (CCM, StemPro) or increasing (StemMacs) mineralization potential with passaging, while aBMMSCs lost this potential after passages 6–7 under all expansion conditions.ConclusionsThese findings indicate there is still a vacant role for development of qualified protocols for clinical-grade expansion of oral MSCs; a key milestone achievement for translation of research from the bench to clinics.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0705-0) contains supplementary material, which is available to authorized users.

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Human deciduous teeth have been proposed as a promising source of mesenchymal stem cells for application in bone and dental tissue engineering. We established cultures of mesenchymal stem cells from the pulp of human deciduous teeth (deciduous teeth stem cells, DTSCs) and analyzed their morphologic, growth, immunophenotypic, and osteo/odontogenic differentiation characteristics using different isolation methods and culturing environments. We compared the biologic behavior of DTSCs isolated either by enzymatic dissociation (DTSCs-ED) or by direct outgrowth from pulp tissue explants (DTSCs-OG). We found that different isolation methods give rise to different populations/lineages of cells with respect to their phenotypic and differentiation characteristics. DTSCs-ED cultures comprised heterogeneous cell populations, whereas DTSCs-OG comprised more homogenous spindle-shaped cells. We have characterized DTSCs as STRO-1(+)/CD146(+)/CD34(+)/CD45(-) cells. However, the percentage of STRO-1(+) and CD34(+) cells was higher in DTSCs-ED (STRO-1, 17.01 ± 5.04%; CD34, 19.79 ± 4.66%) compared to DTSCs-OG cultures (STRO-1, 5.18 ± 2.39%; CD34, 9.94 ± 3.41%), probably as a result of a higher release of stem/progenitor cells from the perivascular niche during enzymatic dissociation. DTSCs isolated using either method displayed an active potential for cellular migration and biomineralization, giving rise to 3D mineralized structures when challenged with dexamethasone, monopotassium phosphate, and β-glycerophosphate. These cellular aggregates progressively expressed differentiation markers of functional odontoblasts, including dentin sialophosphoprotein, bone sialoprotein, osteocalcin, and alkaline phosphatase, having the characteristics of osteodentin. However, in DTSCs-ED, the mineralization rate and the amount of mineralized matrix produced was higher compared to DTSCs-OG cultures. Therefore, DTSCs-ED cells display enhanced biomineralization potential, which might be of advantage for application in clinical therapy.