Advancing Thrombosis Research: A Novel Device for Measuring Clot Permeability

Thromboembolism, a global leading cause of mortality, needs accurate risk assessment for effective prophylaxis and treatment. Current stratification methods fall short in predicting thrombotic events, emphasizing the need for a deeper understanding of clot properties. Fibrin clot permeability, a crucial parameter in hypercoagulable states, impacts clot structure and resistance to lysis. Current clot permeability measurement limitations propel the need for standardized methods. Prior findings underscore the importance of clot permeability in various thrombotic conditions but call for improvements and more precise, repeatable, and standardized methods. Addressing these challenges, our study presents an upgraded, portable, and cost-effective system for measuring blood clot permeability, which utilizes a pressure-based approach that adheres to Darcy's law. By enhancing precision and sensitivity in discerning clot characteristics, this innovation provides a valuable tool for assessing thrombotic risk and associated pathological conditions. In this paper, the authors present a device that is able to automatically perform the permeability measurements on plasma or fibrinogen in vitro-induced clots on specific holders (filters). The proposed device has been tailored to distinguish clot permeability, with high precision and sensitivity, between healthy subjects and high cardiovascular-risk patients. The precise measure of clot permeability represents an excellent indicator of thrombotic risk, thus allowing the clinician, also on the basis of other anamnestic and laboratory data, to attribute a risk score to the subject. The proposed instrument was characterized by performing permeability measurements in plasma and purified fibrinogen clots derived from 17 Behcet patients and 15 sex- and age-matched controls. As expected, our results clearly indicate a significant difference in plasma clot permeability in Behcet patients with respect to controls (0.0533 +/- 0.0199 d vs. 0.0976 +/- 0.0160 d, p < 0.001). This difference was confirmed in the patient's vs. control fibrin clots (0.0487 +/- 0.0170 d vs. 0.1167 +/- 0.0487 d, p < 0.001). In conclusion, our study demonstrates the feasibility, efficacy, portability, and cost-effectiveness of a novel device for measuring clot permeability, allowing healthcare providers to better stratify thrombotic risk and tailor interventions, thereby improving patient outcomes and reducing healthcare costs, which could significantly improve the management of thromboembolic diseases

Strontium substituted hydroxyapatite with β-lactam integrin agonists to enhance mesenchymal cells adhesion and to promote bone regeneration

Multi-functionalization of calcium phosphates to get delivery systems of therapeutic agents is gaining increasing relevance for the development of functional biomaterials aimed to solve problems related to disorders of the muscolo-skeletal system. In this regard, we functionalized Strontium substituted hydroxyapatite (SrHA) with some β-lactam integrin agonists to develop materials with enhanced properties in promoting cell adhesion and activation of intracellular signaling as well as in counteracting abnormal bone resorption. For this purpose, we selected two monocyclic β-lactams on the basis of their activities towards specific integrins on promoting cell adhesion and signalling. The amount of β-lactams loaded on SrHA could be modulated on changing the polarity of the loading solution, from 3.5–24 wt% for compound 1 and from 3.2–8.4 wt% for compound 2. Studies on the release of the β-lactams from the functionalized SrHA in aqueous medium showed an initial burst followed by a steady-release that ensures a small but constant amount of the compounds over time. The new composites were fully characterized. Co-culture of human primary mesenchymal stem cells (hMSC) and human primary osteoclast (OC) demonstrated that the presence of β-lactams on SrHA favors hMSC adhesion and viability, as well as differentiation towards osteoblastic lineage. Moreover, the β-lactams were found to enhance the inhibitory role of Strontium on osteoclast viability and differentiation

A Variant in TBCD Associated with Motoneuronopathy and Corpus Callosum Hypoplasia: A Case Report

Mutations in the tubulin-specific chaperon D (TBCD) gene, involved in the assembly and disassembly of the α/β-tubulin heterodimers, have been reported in early-onset progressive neurodevelopment regression, with epilepsy and mental retardation. We describe a rare homozygous variant in TBCD, namely c.881G>A/p.Arg294Gln, in a young woman with a phenotype dominated by distal motorneuronopathy and mild mental retardation, with neuroimaging evidence of corpus callosum hypoplasia. The peculiar phenotype is discussed in light of the molecular interpretation, enriching the literature data on tubulinopathies generated from TBCD mutations

Tantalum nanoparticles enhance the osteoinductivity of multiscale composites based on poly(lactide-co-glycolide) electrospun fibers embedded in a gelatin hydrogel

Bioresorbable polymeric materials have risen great interest as implants for bone tissue regeneration, since they show substantial advantages with respect to conventional metal devices, including biodegradability, flexibility, and the possibility to be easily modified to introduce specific functionalities. In the present work, an innovative nanocomposite scaffold, properly designed to show biomimetic and osteoinductive properties for potential application in bone tissue engineering, was developed. The scaffold is characterized by a multi-layer structure, completely different with respect to the so far employed polymeric implants, consisting in a poly(D,L-lactide-co-glycolide)/polyethylene glycol electrospun nanofibrous mat sandwiched between two hydrogel gelatin layers enriched with tantalum nanoparticles (NPs). The composition of the electrospun fibers, containing 10 wt% of polyethylene glycol, was selected to ensure a proper integration of the fibers in the gel phase, essential to endow the composite with flexibility and to prevent delamination between the layers. The scaffold maintained its structural integrity after six weeks of soaking in physiological solutions, albeit the gelatin phase was partially released. The combined use of gelatin, bioresorbable electrospun fibers and tantalum NPs endows the final device with biomimetic and osteoinductive properties. Indeed, results of the in vitro tests demonstrate that the obtained scaffolds clearly represent a favorable milieu for normal human bone-marrow derived mesenchymal stem cells viability and osteoblastic differentiation; moreover, inclusion of tantalum NPs in the scaffold improves cell performance with particular regard to early and late markers of osteoblastic differentiation. (C) 2022 Elsevier Ltd. All rights reserved

Mechanical and in vitro biological properties of uniform and graded Cobalt-chrome lattice structures in orthopedic implants

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