Various Hydrogel Types as a Potential In Vitro Angiogenesis Model.

Angiogenesis, the formation of new blood vessels, is a fundamental process in both physiological repair mechanisms and pathological conditions, including cancer and chronic inflammation. Hydrogels are commonly used as in vitro models to mimic the extracellular matrix (ECM) and support endothelial cell behavior during angiogenesis. Mesenchymal stem cells further augment cell and tissue growth and are therefore widely used in regenerative medicine.

Impact of compression forces on different mesenchymal stem cell types regarding orthodontic indication.

The potential of stem cells, for example upper periodontal ligament stem cells from the maxilla (u-PDLSC) and from the mandible (l-PDLSC), adipose-derived mesenchymal stem cells (AD-MSC), and bone marrow-derived mesenchymal stem cells (BM-MSC), with respect to periodontal remodeling and orthodontic treatment is of great importance. In this work, we focus on the comprehensive adaptability of different stem cell types to mechanical forces with the aim to better understanding cell behavior and to refine a new mechanistic approach to investigate periodontal remodeling. We comprehensively analyze stem cells and observe distinct morphological and proliferation changes under compression in dependence on stem cell type.

Pioglitazone treatment mitigates cardiovascular bioprosthetic degeneration in a chronic kidney disease model.

Aims: Chronic kidney disease (CKD) is a risk factor for the development of cardiovascular diseases, e.g., atherosclerosis and calcific aortic valve disease, leading inevitably to valve replacement surgery.

Impact of Fibrin Gel Architecture on Hepatocyte Growth Factor Release and Its Role in Modulating Cell Behavior for Tissue Regeneration.

A novel scaffold design has been created to enhance tissue engineering and regenerative medicine by optimizing the controlled, prolonged release of Hepatocyte Growth Factor (HGF), a powerful chemoattractant for endogenous mesenchymal stem cells. We present a new stacked scaffold that is made up of three different fibrin gel layers, each of which has HGF integrated into the matrix. The design attempts to preserve HGF's regenerative properties for long periods of time, which is necessary for complex tissue regeneration.

Identifying Differences in Molecular Characteristics Relevant for Remodeling of Periodontal Ligament Stem Cells from the Upper and Lower Jaw.

Periodontal defects' localization affects wound healing and bone remodeling, with faster healing in the upper jaw compared to the lower jaw. While differences in blood supply, innervation, and odontogenesis contribute, cell-intrinsic variances may exist. Few studies explored cell signaling in periodontal ligament stem cells (PDLSC), overlooking mandible-maxilla disparitiesUsing kinomics technology, we investigated molecular variances in PDLSC.

Fibrin-Based Hydrogels with Reactive Amphiphilic Copolymers for Mechanical Adjustments Allow for Capillary Formation in 2D and 3D Environments.

This study focuses on enhancing controllable fibrin-based hydrogels for tissue engineering, addressing existing weaknesses. By integrating a novel copolymer, we improved the foundation for cell-based angiogenesis with adaptable structural features. Tissue engineering often faces challenges like waste disposal and nutrient supply beyond the 200 µm diffusion limit.

Type I Interferon, Induced by Adenovirus or Adenoviral Vector Infection, Regulates the Cytokine Response to Lipopolysaccharide in a Macrophage Type-Specific Manner.

Introduction: While TLR ligands derived from microbial flora and pathogens are important activators of the innate immune system, a variety of factors such as intracellular bacteria, viruses, and parasites can induce a state of hyperreactivity, causing a dysregulated and potentially life-threatening cytokine over-response upon TLR ligand exposure. Type I interferon (IFN-αβ) is a central mediator in the induction of hypersensitivity and is strongly expressed in splenic conventional dendritic cells (cDC) and marginal zone macrophages (MZM) when mice are infected with adenovirus. This study investigates the ability of adenoviral infection to influence the activation state of the immune system and underlines the importance of considering this state when planning the treatment of patients.

Solving the insoluble: calciprotein particles mediate bulk mineral transport.

Protein mineral complexes, or calciprotein particles, are formed by calcium, phosphate, and the plasma protein fetuin-A. Crystalline calciprotein particles cause soft tissue calcification, oxidative stress, and inflammation, all well-known complications in chronic kidney disease. The T50 calcification propensity test measures how long it takes for amorphous calciprotein particles to crystallize.

Increased UHMWPE Particle-Induced Osteolysis in Fetuin-A-Deficient Mice.

Particle-induced osteolysis is a major cause of aseptic prosthetic loosening. Implant wear particles stimulate tissue macrophages inducing an aseptic inflammatory reaction, which ultimately results in bone loss. Fetuin-A is a key regulator of calcified matrix metabolism and an acute phase protein.

Application of the mineral-binding protein fetuin-A for the detection of calcified lesions.

Calcium plays an essential role in the biology of vertebrates. Calcium content in body fluids is maintained within a narrow physiologic range by feedback control. Phosphate is equally important for metabolism and is likewise controlled, albeit over a wider range.

Comparative analysis of proliferative and multilineage differentiation potential of human periodontal ligament stem cells from maxillary and mandibular molars.

Background: Clinical experience indicates that wounds in alveolar bone and periodontal tissue heal faster and more efficiently in the maxilla compared with the mandible. Since stem cells are known to have a decisive influence on wound healing and tissue regeneration, the aim of this study was to determine whether differences in proliferation and differentiation of periodontal ligament stem cells (PDLSC) from upper (u-PDLSC) and lower jaw (l-PDLSC) contribute to the enhanced wound healing in the maxilla.

Methods: u-PDLSC and l-PDLSC from the same donor were harvested from the periodontal ligament of extracted human maxillary and mandibular third molars.

Post-translational modifications glycosylation and phosphorylation of the major hepatic plasma protein fetuin-A are associated with CNS inflammation in children.

Fetuin-A is a liver derived plasma protein showing highest serum concentrations in utero, preterm infants, and neonates. Fetuin-A is also present in cerebrospinal fluid (CSF). The origin of CSF fetuin-A, blood-derived via the blood-CSF barrier or synthesized intrathecally, is presently unclear.

Distinct role of mitochondrial function and protein kinase C in intimal and medial calcification .

Introduction: Vascular calcification (VC) is a major risk factor for cardiovascular morbidity and mortality. Depending on the location of mineral deposition within the arterial wall, VC is classified as intimal and medial calcification. Using mineralization assays, we developed protocols triggering both types of calcification in vascular smooth muscle cells (SMCs) following diverging molecular pathways.

A Semi-Automated and Reproducible Biological-Based Method to Quantify Calcium Deposition In Vitro.

Vascular calcification involves a series of degenerative pathologies, including inflammation, changes to cellular phenotype, cell death, and the absence of calcification inhibitors, that concomitantly lead to a loss of vessel elasticity and function. Vascular calcification is an important contributor to morbidity and mortality in many pathologies, including chronic kidney disease, diabetes mellitus, and atherosclerosis. Current research models to study vascular calcification are limited and are only viable at the late stages of calcification development in vivo.

Tissue chaperoning-the expanded functions of fetuin-A beyond inhibition of systemic calcification.

Traditionally, fetuin-A embodies the prototype anti-calcification protein in the blood, preventing cardiovascular calcification. Low serum fetuin-A is generally associated with mineralization dysbalance and enhanced mortality in end stage renal disease. Recent evidence indicates that fetuin-A is a crucial factor moderating tissue inflammation and fibrosis, as well as a systemic indicator of acute inflammatory disease.

Development of the BioHybrid Assay: Combining Primary Human Vascular Smooth Muscle Cells and Blood to Measure Vascular Calcification Propensity.

Background: Vascular calcification is an active process that increases cardiovascular disease (CVD) risk. There is still no consensus on an appropriate biomarker for vascular calcification. We reasoned that the biomarker for vascular calcification is the collection of all blood components that can be sensed and integrated into a calcification response by human vascular smooth muscle cells (hVSMCs).

The E-modulus of the oocyte is a non-destructive measure of zona pellucida hardening.

After fertilization, the oocyte-specific metalloproteinase ovastacin is released and cleaves the zona pellucida protein 2 (ZP2), making the zona pellucida impermeable to sperm. Before fertilization, the zona remains permeable because previously released ovastacin is inhibited by fetuin-B. Consequently, in the absence of fetuin-B, ZP2 cleavage occurs prematurely and leads to infertility of female fetuin-B deficient mice.

Interleukin-1α Is a Central Regulator of Leukocyte-Endothelial Adhesion in Myocardial Infarction and in Chronic Kidney Disease.

Background: Cardiovascular diseases and chronic kidney disease (CKD) are highly prevalent, aggravate each other, and account for substantial mortality. Both conditions are characterized by activation of the innate immune system. The alarmin interleukin-1α (IL-1α) is expressed in a variety of cell types promoting (sterile) systemic inflammation.

Live Imaging of Calciprotein Particle Clearance and Receptor Mediated Uptake: Role of Calciprotein Monomers.

Background: The liver-derived plasma protein fetuin A is a systemic inhibitor of ectopic calcification. Fetuin-A stabilizes calcium phosphate mineral initially as ion clusters to form calciprotein monomers (CPM), and then as larger multimeric consolidations containing amorphous calcium phosphate (primary CPP, CPP 1) or more crystalline phases (secondary CPP, CPP 2). CPM and CPP mediate excess mineral stabilization, transport and clearance from circulation.

Limited proteolysis by acrosin affects sperm-binding and mechanical resilience of the mouse zona pellucida.

The encounter of oocyte and sperm is the key event initiating embryonic development in mammals. Crucial functions of this existential interaction are determined by proteolytic enzymes, such as acrosin, carried in the sperm head acrosome, and ovastacin, stored in the oocyte cortical granules. Ovastacin is released upon fertilisation to cleave the zona pellucida, a glycoprotein matrix surrounding the oocyte.

Fetuin-A is a HIF target that safeguards tissue integrity during hypoxic stress.

Intrauterine growth restriction (IUGR) is associated with reduced kidney size at birth, accelerated renal function decline, and increased risk for chronic kidney and cardiovascular diseases in adults. Precise mechanisms underlying fetal programming of adult diseases remain largely elusive and warrant extensive investigation. Setting up a mouse model of hypoxia-induced IUGR, fetal adaptations at mRNA, protein and cellular levels, and their long-term functional consequences are characterized, using the kidney as a readout.

Mud in the blood: the role of protein-mineral complexes and extracellular vesicles in biomineralisation and calcification.

Protein-mineral interaction is known to regulate biomineral stability and morphology. We hypothesise that fluid phases produce highly dynamic protein-mineral complexes involved in physiology and pathology of biomineralisation. Here, we specifically focus on calciprotein particles, complexes of vertebrate mineral-binding proteins and calcium phosphate present in the systemic circulation and abundant in extracellular fluids - hence the designation of the ensuing protein-mineral complexes as "mud in the blood".

Calciprotein particles: mineral behaving badly?

Purpose Of Review: Calciprotein particles (CPP) are formed in supersaturated solutions of calcium, phosphate and the mineral-binding protein fetuin-A. CPP have garnered considerable interest as potential mediators of mineral stress, but little consideration has been given to their origin, clearance and role in metabolism.

Recent Findings: CPP are made whilst buffering the mineral absorbed from the intestine after a meal or during remodelling of bone matrix.

Rapid calcification propensity testing in blood using a temperature controlled microfluidic polymer chip.

Phosphate toxicity is a major threat to cardiovascular health in chronic kidney disease. It is associated with oxidative stress, inflammation and the accumulation of calcium phosphate commonly known as calcification in soft tissues leading to functional disorders of blood vessels. An improved calcification propensity test for the assessment of phosphate toxicity was developed, which measures the velocity of calcium phosphate mineralization from colloidal precursors in vitro.