Modeling the Effect of Annulus Fibrosus Stiffness on the Stressed State of a Vertebral L1 Body and Nucleus Pulposus.

The investigation examines the transference of stiffness from intervertebral discs (IVDs) to the lumbar body of the L1 vertebra and the interactions among adjacent tissues. A computational model of the vertebra was developed, considering parameters such as cortical bone thickness, trabecular bone elasticity, and the nonlinear response of the nucleus pulposus to external loading. A nonlinear dynamic analysis was performed, revealing certain trends: a heightened stiffness of the annulus fibrosus correlates with a significant reduction in the vertebral body's ability to withstand external loading. At a supplied displacement of 6 mm, the vertebra with a degenerative disc reached its yielding point, whereas the vertebrae with a healthy annulus fibrosus exhibited a strength capacity exceeding 20%. The obtained findings and proposed methodology are potentially useful for biomedical engineers and clinical specialists in evaluating the condition of the annulus fibrosus and predicting its influence on the bone components of the spinal system.

Menstrual Blood-Derived Stem Cell Paracrine Factors Possess Stimulatory Effects on Chondrogenesis In Vitro and Diminish the Degradation of Articular Cartilage during Osteoarthritis.

Articular cartilage is an avascular tissue with a limited capacity for self-regeneration, leading the tissue to osteoarthritis (OA). Mesenchymal stem cells (MSCs) are promising for cartilage tissue engineering, as they are capable of differentiating into chondrocyte-like cells and secreting a number of active molecules that are important for cartilage extracellular matrix (ECM) synthesis. The aim of this study was to evaluate the potential of easily accessible menstrual blood-derived MSC (MenSC) paracrine factors in stimulating bone marrow MSC (BMMSCs) chondrogenic differentiation and to investigate their role in protecting cartilage from degradation in vitro. MenSCs and BMMSCs chondrogenic differentiation was induced using four different growth factors: TGF-ß3, activin A, BMP-2, and IGF-1. The chondrogenic differentiation of BMMSCs was stimulated in co-cultures with MenSCs and cartilage explants co-cultured with MenSCs for 21 days. The chondrogenic capacity of BMMSCs was analyzed by the secretion of four growth factors and cartilage oligomeric matrix protein, as well as the release and synthesis of cartilage ECM proteins, and chondrogenic gene expression in cartilage explants. Our results suggest that MenSCs stimulate chondrogenic response in BMMSCs by secreting activin A and TGF-ß3 and may have protective effects on cartilage tissue ECM by decreasing the release of GAGs, most likely through the modulation of activin A related molecular pathway. In conclusion, paracrine factors secreted by MenSCs may turn out to be a promising therapeutical approach for cartilage tissue protection and repair.

Stimulation of Chondrocyte and Bone Marrow Mesenchymal Stem Cell Chondrogenic Response by Polypyrrole and Polypyrrole/Gold Nanoparticles.

Bone marrow mesenchymal stem cells (BMMSCs) possess a strong ability to differentiate into the chondrogenic lineage, which is important for cartilage regeneration. External stimuli, such as electrical stimulation (ES), are frequently studied for chondrogenic differentiation of BMMSCs; however, the application of conductive polymers such as polypyrrole (Ppy), has never been used for stimulating BMMSCs chondrogenesis in vitro before. Thus, the aim of this study was to evaluate the chondrogenic potential of human BMMSCs after stimulation with Ppy nanoparticles (Ppy NPs) and compare them to cartilage-derived chondrocytes. In this study, we tested Ppy NPs without and with 13 nm gold NPs (Ppy/Au) for BMMSCs and chondrocyte proliferation, viability, and chondrogenic differentiation for 21 days, without the use of ES. The results demonstrated significantly higher amounts of cartilage oligomeric matrix protein (COMP) in BMMSCs stimulated with Ppy and Ppy/Au NPs, as compared to the control. The expression of chondrogenic genes (SOX9, ACAN, COL2A1) in BMMSCs and chondrocytes were upregulated by Ppy and Ppy/Au NPs, as compared to controls. Histological staining with safranin-O indicated higher extracellular matrix production in Ppy and Ppy/Au NPs stimulated samples, as compared to controls. In conclusion, Ppy and Ppy/Au NPs stimulate BMMSC chondrogenic differentiation; however, BMMSCs were more responsive to Ppy, while chondrocytes possessed a stronger chondrogenic response to Ppy/Au NPs.

The Effect of CaV1.2 Inhibitor Nifedipine on Chondrogenic Differentiation of Human Bone Marrow or Menstrual Blood-Derived Mesenchymal Stem Cells and Chondrocytes.

Cartilage is an avascular tissue and sensitive to mechanical trauma and/or age-related degenerative processes leading to the development of osteoarthritis (OA). Therefore, it is important to investigate the mesenchymal cell-based chondrogenic regenerating mechanisms and possible their regulation. The aim of this study was to investigate the role of intracellular calcium (iCa2+) and its regulation through voltage-operated calcium channels (VOCC) on chondrogenic differentiation of mesenchymal stem/stromal cells derived from human bone marrow (BMMSCs) and menstrual blood (MenSCs) in comparison to OA chondrocytes. The level of iCa2+ was highest in chondrocytes, whereas iCa2+ store capacity was biggest in MenSCs and they proliferated better as compared to other cells. The level of CaV1.2 channels was also highest in OA chondrocytes than in other cells. CaV1.2 antagonist nifedipine slightly suppressed iCa2+, Cav1.2 and the proliferation of all cells and affected iCa2+ stores, particularly in BMMSCs. The expression of the CaV1.2 gene during 21 days of chondrogenic differentiation was highest in MenSCs, showing the weakest chondrogenic differentiation, which was stimulated by the nifedipine. The best chondrogenic differentiation potential showed BMMSCs (SOX9 and COL2A1 expression); however, purposeful iCa2+ and VOCC regulation by blockers can stimulate a chondrogenic response at least in MenSCs.

Electrical Stimulation in Cartilage Tissue Engineering.

Electrical stimulation (ES) has been frequently used in different biomedical applications both in vitro and in vivo. Numerous studies have demonstrated positive effects of ES on cellular functions, including metabolism, proliferation, and differentiation. The application of ES to cartilage tissue for increasing extracellular matrix formation is of interest, as cartilage is not able to restore its lesions owing to its avascular nature and lack of cells. Various ES approaches have been used to stimulate chondrogenic differentiation in chondrocytes and stem cells; however, there is a huge gap in systematizing ES protocols used for chondrogenic differentiation of cells. This review focuses on the application of ES for chondrocyte and mesenchymal stem cell chondrogenesis for cartilage tissue regeneration. The effects of different types of ES on cellular functions and chondrogenic differentiation are reviewed, systematically providing ES protocols and their advantageous effects. Moreover, cartilage 3D modeling using cells in scaffolds/hydrogels under ES are observed, and recommendations on reporting about the use of ES in different studies are provided to ensure adequate consolidation of knowledge in the area of ES. This review brings novel insights into the further application of ES in in vitro studies, which are promising for further cartilage repair techniques.

Modeling the Impact of Meniscal Tears on von Mises Stress of Knee Cartilage Tissue.

The present study aims to explore the stressed state of cartilage using various meniscal tear models. To perform this research, the anatomical model of the knee joint was developed and the nonlinear mechanical properties of the cartilage and meniscus were verified. The stress-strain curve of the meniscus was obtained by testing fresh tissue specimens of the human meniscus using a compression machine. The results showed that the more deteriorated meniscus had greater stiffness, but its integrity had the greatest impact on the growth of cartilage stresses. To confirm this, cases of radial, longitudinal, and complex tears were examined. The methodology and results of the study can assist in medical diagnostics for meniscus treatment and replacement.

Cardiovascular Drugs and Osteoarthritis: Effects of Targeting Ion Channels.

Osteoarthritis (OA) and cardiovascular diseases (CVD) share many similar features, including similar risk factors and molecular mechanisms. A great number of cardiovascular drugs act via different ion channels and change ion balance, thus modulating cell metabolism, osmotic responses, turnover of cartilage extracellular matrix and inflammation. These drugs are consumed by patients with CVD for many years; however, information about their effects on the joint tissues has not been fully clarified. Nevertheless, it is becoming increasingly likely that different cardiovascular drugs may have an impact on articular tissues in OA. Here, we discuss the potential effects of direct and indirect ion channel modulating drugs, including inhibitors of voltage gated calcium and sodium channels, hyperpolarization-activated cyclic nucleotide-gated channels, ß-adrenoreceptor inhibitors and angiotensin-aldosterone system affecting drugs. The aim of this review was to summarize the information about activities of cardiovascular drugs on cartilage and subchondral bone and to discuss their possible consequences on the progression of OA, focusing on the modulation of ion channels in chondrocytes and other joint cells, pain control and regulation of inflammation. The implication of cardiovascular drug consumption in aetiopathogenesis of OA should be considered when prescribing ion channel modulators, particularly in long-term therapy protocols.

Protocol for the Isolation of Intact Chondrons from Healthy and Osteoarthritic Human Articular Cartilage.

Chondrons are the main functional microanatomical units in cartilage, consisting of chondrocytes and the directly surrounding pericellular matrix (PCM). They have attracted attention as a more physiological and biomimetic in vitro model for evaluating chondrocyte function and metabolism as compared to single chondrocytes. Chondrons may be more suitable for in vitro studies than primary chondrocytes that have been isolated without PCM since their in situ and in vivo states remain intact: chondrocytes within their PCM do not undergo the rapid dedifferentiation that proliferating single chondrocytes undergo in culture. Therefore, chondrons may be a better model for studying chondrocyte biology and responses to pro-inflammatory and anti-inflammatory cytokines, growth factors and novel therapeutics. In this chapter, we present a concise and unified protocol for enzymatic isolation of intact chondrons from human articular cartilage and determination of their viability.