The bones and joints in the skeletal system are composed of diverse cell types, including vascular niches, bone cells, connective tissue cells and mineral deposits and regulate whole-body homeostasis. The capacity of maintaining strength and generation of blood lineages lies within the skeletal system. Bone harbours blood and immune cells and their progenitors, and vascular cells provide several immune cell type niches. Blood vessels in bone are phenotypically and functionally diverse, with distinct capillary subtypes exhibiting striking changes with age. The bone vasculature has a special impact on osteogenesis and haematopoiesis, and dysregulation of the vasculature is associated with diverse blood and bone diseases. Ageing is associated with perturbed haematopoiesis, loss of osteogenesis, increased adipogenesis and diminished immune response and immune cell production. Endothelial and perivascular cells impact immune cell production and play a crucial role during inflammation. Here, we discuss normal and maladapted vascular niches in bone during development, homeostasis, ageing and bone diseases such as rheumatoid arthritis and osteoarthritis. Further, we discuss the role of vascular niches during bone malignancy.

Thoracoabdominal aortic aneurysms (TAAAs) are rare but serious conditions characterized by dilation of the aorta characterized by remodeling of the vessel wall, with changes in the elastin and collagen content. Individuals with Marfan syndrome have a genetic predisposition for elastic fiber fragmentation and elastin degradation and are prone to early aneurysm formation and progression. Our objective was to analyze the medial collagen characteristics through histological, polarized light microscopy, and electron microscopy methods across the thoracic and abdominal aorta in twenty-five patients undergoing open surgical repair, including nine with Marfan syndrome. While age at surgery differed significantly between the groups, maximum aortic diameter and aneurysm extent did not. Collagen content increased from thoracic to infrarenal segments in both cohorts, with non-Marfan patients exhibiting higher collagen percentages, notably in the infrarenal aorta (729.3 nm vs. 1068.3 nm, p = 0.02). Both groups predominantly displayed mature collagen fibers, with the suprarenal segment containing the highest proportion of less mature fibers. Electron microscopy revealed comparable collagen fibril diameters across segments irrespective of Marfan status. Our findings underscore non-uniform histological patterns in TAAAs and suggest that ECM remodeling involves mature collagen deposition, albeit with lower collagen content observed in the infrarenal aorta of Marfan patients.

Current management guidelines for ascending thoracic aortic aneurysms (aTAA) recommend intervention once ascending or sinus diameter reaches 5–5.5 cm or shows a growth rate of >0.5 cm/year estimated from echo/CT/MRI. However, many aTAA dissections (aTAAD) occur in vessels with diameters below the surgical intervention threshold of <55 mm. Moreover, during aTAA repair surgeons observe and experience considerable variations in tissue strength, thickness, and stiffness that appear not fully explained by patient risk factors. To improve the understanding of aTAA pathophysiology, we established a multi-disciplinary research infrastructure: The Maastricht acquisition platform for studying mechanisms of tissue–cell crosstalk (MAPEX). The explicit scientific focus of the platform is on the dynamic interactions between vascular smooth muscle cells and extracellular matrix (i.e., cell–matrix crosstalk), which play an essential role in aortic wall mechanical homeostasis. Accordingly, we consider pathophysiological influences of wall shear stress, wall stress, and smooth muscle cell phenotypic diversity and modulation. Co-registrations of hemodynamics and deep phenotyping at the histological and cell biology level are key innovations of our platform and are critical for understanding aneurysm formation and dissection at a fundamental level. The MAPEX platform enables the interpretation of the data in a well-defined clinical context and therefore has real potential for narrowing existing knowledge gaps. A better understanding of aortic mechanical homeostasis and its derangement may ultimately improve diagnostic and prognostic possibilities to identify and treat symptomatic and asymptomatic patients with existing and developing aneurysms.

Local biaxial deformation plays a pivotal role in evaluating the tissue state of the ascending aorta and in driving intramural cell-mediated tissue remodeling. Unfortunately, the absence of anatomical markers on the ascending aorta presents challenges in capturing deformation. Utilizing our established intra-operative biaxial strain measurement method, we delineated local biaxial deformation characteristics in patients undergoing aortic valve replacement and coronary artery bypass graft surgery recipients (n = 20), and Aortic Repair surgery patients (n = 47). Expectedly, mean circumferential strains positively correlated with pulse pressure and negatively correlated with age and diameter. A new observation was that the mean axial strains exhibited the same trend as the mean circumferential strains when correlated with pulse pressure, age and diameter. Interestingly, on analyzing local biaxial strains, our findings revealed higher circumferential strains (by 1 %) proximal to the heart compared to distal regions across the cohorts and within each patient cohort. Furthermore, no discernible regional strain distinctions were noted between the medial and lateral sides of the ascending aorta for the entire patient population and individual cohorts. Patients undergoing Aortic Repair surgery indicated lower strains (ranging from 1 to 3 %) as compared to the other cohort. Our approach holds the potential to establish a foundational framework for the integrated examination of the mechanical and biological conditions and their role in ascending aortic aneurysm development.

Biological tissue integrity is actively maintained by cells. It is essential to comprehend how cells accomplish this in order to stage tissue diseases. However, addressing the complexity of a cell's system of interrelated mechanisms poses a challenge. This necessitates a well-structured identification framework and an effective integration of measurements. Here we introduce the use of state-of-the-art frequency-domain system identification techniques combined with an indentation measurement platform to analyze the underlying mechanisms from the perspective of control system theory. The ultimate goal is to explore how mechanical and biological factors are related in induced Pluripotent Stem Cell-derived vascular smooth muscle cells. We study on the frequency-domain analysis for the investigation and characterization of cellular dynamics of smooth muscle cells from the measured data. The measurement model in this study exploits the availability of human tissue and samples, enabling fundamental investigations of vascular tissue disease. This approach using human cell lines holds significant potential to decrease the necessity for animal-based safety and efficacy studies. The focus of this review is to investigate the cellular dynamics underlying the myogenic response and to demonstrate the practicability of employing a nano-indentation measurement setup for the broadband frequency-domain characterization of induced Pluripotent Stem Cell-derived vascular smooth muscle cells.