Search

Background: Platelets and lymphocytes levels are important in assessing systemic disorders, reflecting inflammatory and immune responses. This study investigated the relationship between blood parameters (platelet count (PLT), mean platelet volume (MPV), lymphocyte count (LINF), and platelet-to-lymphocyte ratio (PLR)) and osteoarthritis (OA) severity, considering age, sex, and body mass index (BMI). Methods: Patients aged ≥40 years were included in this cross-sectional study and divided into groups based on knee OA severity using the Kellgren–Lawrence (KL) grading system. A logistic regression model, adjusted for confounders, evaluated the ability of PLT, MPV, LINF, and PLR to categorize OA severity. Model performance in terms of accuracy, sensitivity, and specificity was assessed using ROC curves. Results: The study involved 245 OA patients (51.4% female, 48.6% male) aged 40–90 years, 35.9% with early OA (KL < 3) and 64.1% moderate/severe OA (KL ≥ 3). Most patients (60.8%) were aged ≥60 years, and BMI was <25 kg/m2 in 33.9%. The model showed that a 25-unit increase in PLR elevates the odds of higher OA levels by 1.30 times (1-unit OR = 1.011, 95% CI [1.004, 1.017], p < 0.005), while being ≥40 years old elevates the odds by 4.42 times (OR 4.42, 95% CI [2.46, 7.95], p < 0.0005). The model's accuracy was 73.1%, with 84% sensitivity, 52% specificity, and an AUC of 0.74 (95% CI [0.675, 0.805]). Conclusions: Higher PLR increases the likelihood of moderate/severe OA, suggesting that monitoring these biomarkers could aid in early detection and management of OA severity. Further research is warranted to cross-validate these results in larger populations. [ABSTRACT FROM AUTHOR]

Osteochondral lesions, when not properly treated, may evolve into osteoarthritis (OA), especially in the elderly population, where altered joint function and quality are usual. To date, a collagen/collagen–magnesium–hydroxyapatite (Col/Col-Mg-HAp) scaffold (OC) has demonstrated good clinical results, although suboptimal subchondral bone regeneration still limits its efficacy. This study was aimed at evaluating the in vitro osteogenic potential of this scaffold, functionalized with two different strategies: the addition of Bone Morphogenetic Protein-2 (BMP-2) and the incorporation of strontium (Sr)-ion-enriched amorphous calcium phosphate (Sr-ACP) granules. Human osteoblasts were seeded on the functionalized scaffolds (OC+BMP-2 and OC+Sr-ACP, compared to OC) under stress conditions reproduced with the addition of H2O2 to the culture system, as well as in normal conditions, and evaluated in terms of morphology, metabolic activity, gene expression, and matrix synthesis. The OC+BMP-2 scaffold supported a better osteoblast morphology and stimulated scaffold colonization, cell activity, and extracellular matrix secretion, especially in the stressed culture environment but also in normal culture conditions, with increased expression of genes related to osteoblast differentiation. In conclusion, the incorporation of BMP-2 into the Col/Col-Mg-HAp scaffold also represents an improvement of the osteochondral scaffold in more challenging conditions, supporting further preclinical studies to optimize it for use in clinical practice. [ABSTRACT FROM AUTHOR]

Recently, our group described the application of vertebral bone marrow (vBMA) clot as a cell therapy strategy for spinal fusion. Its beneficial effects were confirmed in aging-associated processes, but the influence of gender is unknown. In this study, we compared the biological properties of vBMA clots and derived vertebral mesenchymal stem cells (MSCs) from female and male patients undergoing spinal fusion procedures and treated with vBMA clot. We analyzed the expression of growth factors (GFs) in vBMA clots and MSCs as well as morphology, viability, doubling time, markers expression, clonogenicity, differentiation ability, senescence factors, Klotho expression, and HOX and TALE gene profiles from female and male donors. Our findings indicate that vBMA clots and derived MSCs from males had higher expression of GFs and greater osteogenic and chondrogenic potential compared to female patients. Additionally, vBMA-clot-derived MSCs from female and male donors exhibited distinct levels of HOX and TALE gene expression. Specifically, HOXA1, HOXB8, HOXD9, HOXA11, and PBX1 genes were upregulated in MSCs derived from clotted vBMA from male donors. These results demonstrate that vBMA clots can be effectively used for spinal fusion procedures; however, gender-related differences should be taken into consideration when utilizing vBMA-clot-based studies to optimize the design and implementation of this cell therapy strategy in clinical trials. [ABSTRACT FROM AUTHOR]

Curcumin has numerous biological activities and pharmaceutical applications related to its ability to inhibit reactive oxygen species. Herein, strontium-substituted monetite (SrDCPA) and strontium-substituted brushite (SrDCPD) were synthesized and further functionalized with curcumin with the aim to develop materials that combine the anti-oxidant properties of the polyphenol, the beneficial role of strontium toward bone tissue, and the bioactivity of calcium phosphates. Adsorption from hydroalcoholic solution increases with time and curcumin concentration, up to about 5–6 wt%, without affecting the crystal structure, morphology, and mechanical response of the substrates. The multi-functionalized substrates exhibit a relevant radical scavenging activity and a sustained release in phosphate buffer. Cell viability, morphology, and expression of the most representative genes were tested for osteoclast seeded in direct contact with the materials and for osteoblast/osteoclast co-cultures. The materials at relatively low curcumin content (2–3 wt%) maintain inhibitory effects on osteoclasts and support the colonization and viability of osteoblasts. The expressions of Alkaline Phosphatase (ALPL), collagen type I alpha 1 chain (COL1A1), and osteocalcin (BGLAP) suggest that curcumin reduces the osteoblast differentiation state but yields encouraging osteoprotegerin/receptor activator for the NFkB factor ligand (OPG/RANKL) ratio. [ABSTRACT FROM AUTHOR]

Gender-based violence is a global public health issue and major human rights concern. It is also a type of violence that is disproportionately experienced by women and girls. This study is the first to examine multiple implementation process (dosage, fidelity, and adaptation) effects on changes in anticipated outcomes of a school-based bystander program targeting gender-based violence, Mentors in Violence Prevention (MVP). Data were collected from two participant groups: mentees (students receiving MVP) and mentors (students delivering MVP), across nine participating high schools. The mentee sample comprised 698 students (about 48.9% males and 49.7% females), aged 11 to 14 years old (M = 11.86, SD = 0.64). The mentor sample comprised 118 students (17.80% males, 82.20% females), aged 15 to 18 years old (M = 16.42, SD = 0.60). Anticipated outcomes were changes in bystanders' attitudes, social influences, control perceptions, intentions, willingness, and intervention behavior, measured using mentees' self-reports at two time points approximately 1 year apart. Implementation processes were measured using mentors' self-reports. Analyses revealed no effects for any of the implementation variables across changes in any of the outcomes measured. These results highlight important implications for the implementation of the MVP program going forward, given its widespread implementation in the United Kingdom. Possible ways that MVP may be enhanced in future are discussed. For example, furthering understanding into how gender-based violence and bystander intervention are addressed and framed during MVP lessons would give more insight into how the current implementation of the program can be improved to maximize its potential benefits. [ABSTRACT FROM AUTHOR]

Osteoarthritis is a chronic inflammatory disease that affects all of the joints, especially those of the elderly. Aging is a natural and irreversible biological process implicated in the pathophysiology of many chronic diseases, such as osteoarthritis. Inflammation and oxidative stress are the main factors involved in osteoarthritis and aging, respectively, with the production of several pro-inflammatory cytokines such as Interleukin 1β (IL1β) and reactive oxygen species. The aim of the study was to set-up an in vitro model of osteoarthritis and aging, focusing on the sex differences by culturing male and female fibroblast-like synoviocytes (FLSs) with IL1β, hydrogen peroxide (H2O2), IL1β+H2O2 or a growth medium (control). IL1β+H2O2 reduced the cell viability and microwound healing potential, increased Caspase-3 expression and reactive oxygen species and IL6 production; IL1β increased IL6 production more than the other conditions did; H2O2 increased Caspase-3 expression and reactive oxygen species production; Klotho expression showed no differences among the treatments. The FLSs from female donors demonstrated a better response capacity in unfavorable conditions of inflammation and oxidative stress than those from the male donors did. This study developed culture conditions to mimic the aging and osteoarthritis microenvironment to evaluate the behavior of the FLSs which play a fundamental role in joint homeostasis, focusing on the sex-related aspects that are relevant in the osteoarthritis pathophysiology. [ABSTRACT FROM AUTHOR]

This study augmented the Prototype Willingness Model (PWM) to assess reactive and deliberative decision‐making underpinning bystander intervention in gender‐based violence contexts. There were 2079 participants (50% male, 49% female, and 1% unreported), aged 11–15 years old (M = 12.32, SD = 0.91), attending 19 secondary schools across Scotland. Participants self‐reported the augmented PWM variables, then their intervention behaviour approximately 1 month later. Path analyses mostly supported the predicted relationships between positive and negative bidimensional attitudes, subjective norms, prototype perceptions, perceived behavioural control, and self‐efficacy on intentions and willingness. Willingness predicted positive (speaking with a teacher) and negative (doing nothing) intervention in less serious violence. Self‐efficacy predicted negative intervention in more serious violence. Subjective norms positively moderated the attitudes–intentions relationship. Overall, the results suggested that reactive (willingness) more so than deliberative (intention) decision‐making account for intervention when young people witness gender‐based violence. Additionally, the findings highlight the complexity of bystander intervention decision‐making, where adding control perceptions, bidimensional attitudes, and moderators have independent contributions. Furthermore, self‐comparison to the typical bystander who positively intervenes (prototype perceptions) was the strongest predictor of intentions and willingness, highlighting in a novel way the importance of image and group membership on decision‐making. [ABSTRACT FROM AUTHOR]

Monetite and brushite are regarded with increasing interest for the preparation of biomaterials for applications in the musculoskeletal system. Herein, we investigated the influence of strontium substitution in the structures of these two phosphates on bone cell response. To achieve this aim, co-cultures of human primary osteoclasts and human osteoblast-like MG63 cells were tested on strontium-substituted monetite and strontium-substituted brushite, as well as on monetite and brushite, as controls. In both structures, strontium substitution for calcium amounted to about 6 at% and provoked enlargement of the cell parameters and morphologic variations. Cumulative release in physiological solution increased linearly over time and was greater from brushite (up to about 160 and 560 mg/L at 14 days for Sr and Ca, respectively) than from monetite (up to about 90 and 250 mg/L at 14 days for Sr and Ca, respectively). The increasing viability of osteoblast-like cells over time, with the different expression level of some typical bone markers, indicates a more pronounced trigger toward osteoblast differentiation and osteoclast inhibition by brushite materials. In particular, the inhibition of cathepsin K and tartrate-resistant acid phosphatase at the gene and morphological levels suggests strontium-substituted brushite can be applied in diseases characterized by excessive bone resorption. [ABSTRACT FROM AUTHOR]

Human bones are biological examples of functionally graded lattice capable to withstand large in vivo loading and allowing optimal stress distribution. Disruption of bone integrity may require biocompatible implants capable to restore the original bone structure and properties. This study aimed at comparing mechanical properties and biological behavior in vitro of uniform (POR‐FIX) and graded (POR‐VAR) Cobalt‐chrome alloy lattice structures manufactured via Selective Laser Melting. In compression, the POR‐VAR equivalent maximum stress was about 2.5 times lower than that of the POR‐FIX. According to the DIC analysis, the graded lattice structures showed a stratified deformation associated to unit cells variation. At each timepoint, osteoblast cells were observed to colonize the surface and the first layer of both scaffolds. Cell activity was always significantly higher in the POR‐VAR (p < 0.0005). In terms of gene expression, the OPG/RANKL ratio increased significantly over time (p < 0.0005) whereas IL1β and COX2 significantly decreased (7 day vs 1 day; p < 0.0005) in both scaffolds. Both uniform‐ and graded‐porosity scaffolds provided a suitable environment for osteoblasts colonization and proliferation, but graded structures seem to represent a better solution to improve stress distribution between implant and bone of orthopedic implants. [ABSTRACT FROM AUTHOR]

Abstract Background Although progress has been made in the treatment of articular cartilage lesions, they are still a major challenge because current techniques do not provide satisfactory long-term outcomes. Tissue engineering and the use of functional biomaterials might be an alternative regenerative strategy and fulfill clinical needs. Decellularized extracellular matrices have generated interest as functional biologic scaffolds, but there are few studies on cartilage regeneration. The aim of this study was to evaluate in vitro the biological influence of a newly developed decellularized human dermal extracellular matrix on two human primary cultures. Methods Normal human articular chondrocytes (NHAC-kn) and human mesenchymal stromal cells (hMSC) from healthy donors were seeded in polystyrene wells as controls (CTR), and on decellularized human dermis batches (HDM_derm) for 7 and 14 days. Cellular proliferation and differentiation, and anabolic and catabolic synthetic activity were quantified at each experimental time. Histology and scanning electron microscopy were used to evaluate morphology and ultrastructure. Results Both cell cultures had a similar proliferation rate that increased significantly (p < 0.0005) at 14 days. In comparison with CTR, at 14 days NHAC-kn enhanced procollagen type II (CPII, p < 0.05) and aggrecan synthesis (p < 0.0005), whereas hMSC significantly enhanced aggrecan synthesis (p < 0.0005) and transforming growth factor-beta1 release (TGF-β1, p < 0.0005) at both experimental times. Neither inflammatory stimulus nor catabolic activity induction was observed. By comparing data of the two primary cells, NHAC-kn synthesized significantly more CPII than did hMSC at both experimental times (p < 0.005), whereas hMSC synthesized more aggrecan at 7 days (p < 0.005) and TGF-β1 at both experimental times than did NHAC-kn (p < 0.005). Conclusions The results obtained showed that in in vitro conditions HDM_derm behaves as a suitable scaffold for the growth of both well-differentiated chondrocytes and undifferentiated mesenchymal cells, thus ensuring a biocompatible and bioactive substrate. Further studies are mandatory to test the use of HDM_derm with tissue engineering to assess its therapeutic and functional effectiveness in cartilage regeneration.

Over the last decade, advances in additive manufacturing have allowed to obtain complex 3D porous lattice in materials suitable for orthopedic applications. Whereas 3D‐melted titanium alloys have been extensively investigated, little is the current knowledge on the feasibility of bone‐replicating CoCr porous scaffolds manufactured via selective laser melting (SLM). Moreover, the effect of topography on bone cells viability and proliferation has not been fully explored yet. Small cylindrical porous lattices were modeled from micro‐CT images of human trabecular bone, and from the repetition of spherical‐hollow and body‐centered cubic unit cells, and manufactured via SLM from CoCr powder. Macro‐ and microcharacterization of the porous samples were assessed using optical microscope, micro‐CT, and SEM. The scaffolds mechanical properties, measured via ISO testing, compared well with those of the human bone. Osteoblast‐like cells proliferation and viability were assessed in vitro, and compared to those cultured on a standard nonporous implant‐to‐bone interface, showing steady increase on all geometries over time. SEM analysis confirmed the quality of cells morphology, spread, and organization on all lattices. The SLM process appeared not to alter the biocompatibility of CoCr; however, 15–100 μm irregularities and macroalterations were observed in the porous scaffolds with respect to the 3D nominal models. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2343–2353, 2019. [ABSTRACT FROM AUTHOR]

MRI guided Focused Ultrasound (MRgFUS) has shown to be effective therapeutic modality for non-invasive clinical interventions in ablating of uterine fibroids, in bone metastasis palliative treatments, and in breast, liver, and prostate cancer ablation. MRgFUS combines high intensity focused ultrasound (HIFU) with MRI images for treatment planning and real time thermometry monitoring, thus enabling non-invasive ablation of tumor tissue. Although in the literature there are several studies on the Ultrasound (US) effects on cell in culture, there is no systematic evidence of the biological effect of Magnetic Resonance guided Focused Ultrasound Surgery (MRgFUS) treatment on osteosarcoma cells, especially in lower dose regions, where tissues receive sub-lethal acoustic power. The effect of MRgFUS treatment at different levels of acoustic intensity (15.5-49 W/cm2) was investigated on Mg-63 and Saos-2 cell lines to evaluate the impact of the dissipation of acoustic energy delivered outside the focal area, in terms of cell viability and osteogenic differentiation at 24 h, 7 days, and 14 days after treatment. Results suggested that the attenuation of FUS acoustic intensities from the focal area (higher intensities) to the "far field" (lower intensities) zones might determine different osteosarcoma cell responses, which range from decrease of cell proliferation rates (from 49 W/cm2 to 38.9 W/cm2) to the selection of a subpopulation of heterogeneous and immature living cells (from 31.1 W/cm2 to 15.5 W/cm2), which can clearly preserve bone tumor cells. [ABSTRACT FROM AUTHOR]

Low-intensity pulsed ultrasound (LIPUS) as an adjuvant therapy in in vitro and in vivo bone engineering has proven to be extremely useful. The present study aimed at investigating the effect of 30 mW/cm² LIPUS stimulation on commercially available human mesenchymal stem cells (hMSCs) cultured in basal or osteogenic medium at different experimental time points (7, 14, 21 days). The hypothesis was that LIPUS would improve the osteogenic differentiation of hMSC and guarantying the maintenance of osteogenic committed fraction, as demonstrated by cell vitality and proteomic analysis. LIPUS stimulation (a) regulated the balance between osteoblast commitment and differentiation by specific networks (activations of RhoA/ROCK signaling and upregulation of Ribosome constituent/Protein metabolic process, Glycolysis/Gluconeogenesis, RNA metabolic process/Splicing and Tubulins); (b) allowed the maintenance of a few percentage of osteoblast precursors (21 days CD73+/CD90+: 6%; OCT-3/4+/NANOG+/SOX2+: 10%); (c) induced the activation of osteogenic specific pathways shown by gene expression (early: ALPL, COL1A1, late: RUNX2, BGLAP, MAPK1/6) and related protein release (COL1a1, OPN, OC), in particular in the presence of osteogenic soluble factors able to mimic bone microenvironment. To summarize, LIPUS might be able to improve the osteogenic commitment of hMSCs in vitro, and, at the same time, enhance their osteogenic differentiation. [ABSTRACT FROM AUTHOR]