Nano-mechanical mapping of human and porcine abdominal aortic aneurysm.

Improvement of calcified tendonitis following human placenta extract injection: A retrospective, single-arm, multicenter observational study.

Bone is a dynamic tissue that responds to mechanical forces and possesses intrinsic mechanoelectrical activity. Recently, electrically conductive polymers have emerged as stimulating biomaterials for bone tissue engineering. However, the effect of conductive scaffolds under mechanical stimulation towards bone formation remains unclear. This study presents the development of electrically conductive, mechanoactive porous scaffolds, and the validation of their osteogenic capacity under mechanical stimulation. The developed scaffolds contain poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) into a double polymeric network comprising poly(vinyl alcohol) (PVA) and gelatin (Gel). PEDOT-containing scaffolds demonstrated superior electrical conductivity, increased surface porosity, and an elevated Young modulus of 2.7 ± 0.4 MPa compared to the PVA/Gel control. Pre-osteoblastic cells cultured within the conductive, mechanoactive scaffolds under uniaxial compression showed increased cell viability, calcium influx, and upregulation of osteogenic markers. Mechanical loading enhanced the activation of the mechanotransduction markers YAP/TAZ, upregulated alkaline phosphatase activity, collagen secretion, and calcium deposition, particularly in PEDOT-containing scaffolds, with hydroxyapatite formation on day 21. In vivo subcutaneous implantation of the developed scaffolds indicated lack of any adverse immune responses. These results highlight the great potential of the developed electroactive, mechanoresponsive scaffolds as biomimetic substrates to enhance osteogenesis under mechanical stimulation.

TIMP3 attenuates vascular calcification by restoring autophagy in vascular smooth muscle cells through the STAT1/FOXO1 pathway.

ZIF-67-anchored halloysite nanotubes infused in chitosan hydrogel for enhanced bone tissue engineering.

Machine learning approaches to reveal pinealocyte changes in ageing and Alzheimer's disease.

Piezo1 activation mediates stiffness-induced aortic medial calcification: Pharmacological evidence from agonist and antagonist studies.

lincRNA-p21 drives apoptosis and calcification of vascular smooth muscle cell via small extracellular vesicles under hyperphosphatemic conditions in chronic kidney disease.

Chronic kidney disease (CKD) is a complicated systemic disease displaying various pathophysiological symptoms including mineral bone disorder (CKD-MBD). Ideally, early intervention for CKD-MBD would be desirable, however, there is not enough evidence regarding treatment of CKD-MBD, especially in its early stages, due to its multifactorial pathophysiology and the difficulty in generating adequate animal models. In this study, we evaluated the efficacy of a tissue nonspecific alkaline phosphatase (TNAP) inhibitor, SBI-425 in a CKD-MBD animal model, produced by a combination of nephrectomy and high inorganic phosphate (Pi) diet. This combination induced renal damage, and significantly elevated blood urea nitrogen (BUN). Plasma levels of fibroblast growing factor 23 (FGF-23), parathyroid hormone (PTH) and phosphate were also elevated, leading to ectopic calcification in the kidneys, particularly in the renal tubules. We orally administered SBI-425 twice daily for 12 weeks at doses of 1 and 10 mg/kg, and this treatment significantly inhibited the progression of calcium deposition in the renal tubules. Furthermore, SBI-425 effectively prevented the deterioration of plasma parameters, BUN, FGF-23, PTH, and phosphate. In conclusion, our findings suggest that TNAP inhibition can effectively slow the progression of CKD-MBD by inhibiting the calcification in the renal tubules. These results may have implications for better clinical care of patients with CKD.

Skin Disorders in Kidney Disease: Core Curriculum 2026.

ATF4 transcriptional regulation of OMD and STC2 drives vascular calcification progression via the PI3K/AKT pathway.

Mechanical stress accelerates vascular calcification by Piezo1/BMP2 of vascular smooth muscle cells.

Maclurin promotes extracellular matrix formation in osteoblasts via PI3K/Akt pathway activation.

Membrane calcification-reinforced tumor therapy mediated by versatile hollow manganese dioxide nanoplatform.

Medial arterial calcification, ectopic deposition of calcium phosphate crystals in the media, causes aortic stiffness which is associated with the mortality of cardiovascular diseases. Previous studies clarified several factors which are related to disease progression processes, on the contrary, inducing factors of medial arterial calcification remain obscure. In this study, we performed pathological analyses of the aorta in an experimental animal model under the condition of hypoperfusion to understand unexplored events underlying medial arterial calcification. The area of calcium deposition varied with the severity of hypoperfusion, and the extent of calcium deposition was highest under conditions of severe hypoperfusion. Thinning of the media, destruction of elastic fibers, and increased transformation marker of vascular smooth muscle cells into osteoblast-like cells were observed earlier than calcium deposition. Time-dependent observations of the hypoperfusion-induced aorta show the flattening of elastic fibers and death of medial cells prior to calcium phosphate deposition, followed by the formation of microvoids which were used as scaffolds for calcium phosphate crystal formation. These data showed that aortic wall hypoperfusion can be an initiating factor of calcium phosphate deposition in the arterial media.

Quantification of the calcific burden is valuable in percutaneous coronary intervention (PCI) planning and in research to assess its changes after pharmacotherapies targeting plaque progression. In intravascular ultrasound (IVUS) images this analysis is currently performed manually and time consuming. To overcome these limitations, we introduce a deep-learning (DL) method for seamless detection of the calcific tissue. IVUS images from 197 vessels were analysed by an expert who identified the presence of calcium, and these estimations were used to train a DL model for fast detection of calcific deposits. The output of the model was tested in a set of 30 vessels against the estimations of the two experts. Comparison was performed at a frame-, lesion- and segment level. In total 26,211 frames were included in the training and 5,138 in the test set. The estimations of the DL method for the presence of calcium were similar to the experts (kappa 0.842 and 0.848, p < 0.001), while the correlation between the DL approach and the two experts for the arc of calcium (0.946 and 0.947, p < 0.001) and calcific area (0.745 and 0.706, p < 0.001) were high. Lesion- (0.971 and 0.990, p < 0.001) and segment-level analysis (0.980 and 0.981, p < 0.001) demonstrated a high correlation between the method and the two experts for calcific burden. The proposed DL method is able to accurately detect the calcific tissue and quantify its burden. These features render it useful in research and are expected to facilitate its application in the clinical workflows to guide PCI.

While the hydrolase activity of soluble epoxide hydrolase (sEH) reduces vascular calcification, it is not known whether the phosphatase activity of sEH (sEH-P) is also involved. Pharmacological and genetic inhibition of sEH-P reduced the increased calcium deposition in rat aortic rings cultured under high-phosphate conditions. This was associated with decreased mRNA expression of the osteochondrogenic markers Msx2 and Sox9. Deendothelialization of the aortic rings abolished this anticalcifying effect, while the calcification of human aortic smooth muscle cells was unaffected by sEH-P inhibition, suggesting a predominant role of the endothelium. Endothelial NO release did not appear to contribute, but an increased level of the calcification inhibitor pyrophosphate anions (PPi) was observed in the culture supernatant of aortic rings when sEH-P was inhibited. In vitro experiments demonstrated that PPi is a substrate of sEH-P, and that inhibiting sEH-P prevented the high-phosphate induced decrease of PPi in human aortic endothelial cells. Furthermore, the aortic calcification related to chronic kidney disease induced by subtotal nephrectomy was reduced in sEH-P-deficient rats compared to wild-type rats. This was associated with an improvement in flow-induced isolated mesenteric artery dilatation and a reduction of cardiac hypertrophy and fibrosis. Vascular calcification is regulated by sEH-P through the metabolism of endothelial PPi. The prevention of vascular calcification, together with the reduction in vascular dysfunction and cardiac remodeling, suggests that inhibiting sEH-P may help to prevent the cardiovascular complications associated with chronic kidney disease.

BACKGROUNDPathological calcification is a common feature of many diseases. Calcifying nanoparticles (CNPs) are considered potential inducers of this abnormal calcification, but their specific effects on bone marrow mesenchymal stem cells (BMSCs) remain unclear. BMSCs are key cells in bone formation and repair, and their aberrant apoptosis and calcification are closely related to disease progression.AIMTo explore whether CNPs can induce apoptosis and calcification in BMSCs and analyzed the relationship between these processes. The differential effects of CNPs and nanoscale hydroxyapatites (nHAPs) in inducing apoptosis and calcification in BMSCs were also compared.METHODSCNPs obtained in the early stage were identified by electron microscopy and particle size analysis. BMSCs were cultured with various treatments, including different concentrations of nHAPs, CNPs [2 McFarland (MCF) turbidity, 4 MCF, 6 MCF], and a transforming growth factor (TGF)-β inhibitor (SB431542) for 72 hours. The isolated CNPs exhibited the expected sizes and shapes.RESULTSExposure to CNPs and nHAPs suppressed cell proliferation and promoted apoptosis in a concentration-dependent manner, with CNPs exhibiting significantly stronger effects. Alizarin Red staining indicated an increase in calcium deposition with exposure to increasing concentrations of nHAPs and CNPs. Quantitative reverse-transcription polymerase chain reaction results indicated that medium concentrations of nHAPs and CNPs significantly enhanced the expression of pro-apoptotic and pro-calcification markers, whereas the expression of anti-apoptotic Bcl-2 was reduced compared with untreated controls. Western blotting results showed that medium concentrations of CNPs and nHAPs increased the expression of osteopontin, bone morphogenetic protein-2, TGF-β/Smad, Bax, and caspase-3 and decreased Bcl-2 expression compared with controls.CONCLUSIONCNPs and nHAPs induced apoptosis and calcification in BMSCs, with CNPs being the most potent. Additionally, the TGF-β inhibitor SB431542 significantly reduced the occurrence of apoptosis and calcification. A correlation was found between apoptosis and calcification, which is likely mediated through the TGF-β/Smad signaling pathway.

Vibration-assisted orthodontic treatment accelerates tooth movement and reduces complications associated with prolonged interventions. While vibration has been shown to enhance osteogenic potential in bone marrow-derived mesenchymal stem cells (MSCs), its effects on dental tissue-derived MSCs remain unclear. This study investigated the impact of acoustic-frequency vibratory stimulation (AFVS) on gingival-tissue-derived MSCs (GT-MSCs) at 20 Hz and 60 Hz under both basal and osteogenic conditions. A custom vibratory platform was developed, and GT-MSCs were assessed for viability, proliferation, and osteogenic differentiation. Resazurin assay, Calcein-AM staining, and vimentin immunohistochemistry were used to evaluate cell viability, proliferation, and morphology, while Alizarin Red staining and calcium accumulation assays measured extracellular matrix mineralization at 7, 14, and 21 days. A Reverse-Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) reaction was performed to quantify osteogenic markers (colagen type I [COL-I], osteopontin [OPN], and alkaline phosphatase [ALP]), and protein expression for COL-I and OPN was confirmed by immunohistochemistry. The results showed that AFVS at 20 Hz and 60 Hz enhanced osteogenic differentiation in GT-MSCs compare with other groups. Extracellular matrix mineralisation increased significantly, with 60 Hz resulting in the highest calcium deposition. Transcript levels of COL-I and OPN were markedly upregulated at 60 Hz, indicating a frequency-dependent response. Cell proliferation was also promoted, with optimal results observed at 60 Hz compare with other groups. These findings highlight the role of mechanical stimulation in enhancing the osteogenic potential of GT-MSCs, suggesting that AFVS is a promising tool for regenerative and orthodontic treatments. This study provides new insights into the frequency-specific effects of vibration, supporting the use of vibration therapy strategies in dental applications.

One of the recent innovations in the field of hard tissue regeneration is the development of energy-harvesting self-powered implants. Self-powered implants are known for providing extrinsic electrical stimulations to the defective sites of bone, resulting in accelerated bone regeneration. Towards this end, our study focuses on the development of electroactive BaTiO3-modified poly(vinylidene) fluoride (PVDF) self-powered hybrid scaffolds using solvent casting and hot compression molding. The power developed by PVDF, PVDF-15 wt % BaTiO3 (PVDF-15BT), PVDF-25 wt % BaTiO3 (PVDF-25BT), and PVDF-35 wt % BaTiO3 (PVDF-35BT) are ∼0.591 μW/cm2, ∼5.049 μW/cm2, ∼6.300 μW/cm2, and ∼7.516 μW/cm2, respectively. The polarizability of the hybrid scaffolds was assessed using relative permittivity, AC conductivity, P-E hysteresis analysis, and energy density measurements. The incorporation of BT filler significantly enhances the dielectric and piezoelectric behaviors. MG-63 cell culture studies were performed to assess cytocompatibility through fluorescence imaging and viability assays. Osteogenic potential was evaluated via Alkaline Phosphatase (ALP) activity and Alizarin Red S staining for calcium deposition, while hemocompatibility tests confirmed the materials' blood-contact safety. Cell proliferation, osteogenic differentiation (ALP), hemocompatibility, and calcium deposition of osteoblast-like MG-63 cells are substantially augmented. These outcomes recommend that BT-modified PVDF self-powered hybrid scaffolds are suitable for hard tissue regeneration.