Properties Of Blood Clots Research Articles

Blood clot properties, thrombin generation, and platelet activation in patients with dysglycemia and established atherosclerotic cardiovascular disease: The CASCARA study.

There is a strong link between coronary artery disease (CAD), type 2 diabetes (T2D) on one hand, and altered fibrin clot properties, including increased clot density, and unfavorable fibrin clot structure on the other. T2D-related changes in fibrin clots can increase cardiovascular (CV) disease risk, including future CV events. We aimed to assess fibrin clot properties, thrombin generation, and platelet activation in CAD patients with prediabetes (PD) or T2D, compared to CAD patients without glycemic disorders. We allocated patients to three groups: 1) Those with angiographically established CAD but without glycemic abnormalities (CAD group); 2) individuals with PD and established CAD (CAD+PD group); and 3) patients with T2D and CAD (CAD+T2D group). We conducted comparisons across these groups for thrombin generation, fibrin clot permeability, fibrin clot lysis, and platelet activation. The final analysis included 116 eligible patients: 1) CAD group (n = 31); 2) CAD+PD (n = 42); and 3) CAD+T2D (n = 43). The CAD+T2D patients enrolled had well-controlled T2D (median HbA1c level of 5.90%; IQR: 5.7%-6.3%). We found no significant differences in thrombin generation, fibrin clot properties, or platelet activation markers across the three analyzed groups (all P-values >0.20). However, elevated interleukin-6 (IL-6) levels were noted in both the highest and lowest glucose concentration quartiles. Additionally, a substantial increase in endogenous thrombin potential (ETP) was observed in patients in the highest glycated hemoglobin quintile. Individuals with established CAD and concomitant PD or well-controlled T2D exhibited comparable fibrin clot phenotypes, thrombin generation potential, and platelet activation when compared to CAD patients without dysglycemia.

Hyperelasticity of blood clots: Bridging the gap between microscopic and continuum scales

The biomechanical properties of blood clots, which are dictated by their compositions and micro-structures, play a critical role in determining their fates, i.e., occlusion, persistency, or embolization in the human circulatory system. While numerous constitutive models have emerged to describe the biomechanics of blood clots, most of these models have primarily focused on the macroscopic deformation of the clots and the resultant strain-stress correlations without depicting the microscopic contributions from their structural components, such as fibrin fibers, fibrin network and red blood cells. This work addresses the gap in current scientific understanding by quantifying how changes in the microstructure of blood clots affect its mechanical responses under different external stresses. We leverage our previous published work to develop a hyperelastic potential model for blood clots, which incorporates six distinct strain-energy components to describe the alignment of fibers, the entropic and enthalpic stretching of fibrin fibers, the buckling of these fibers, clot densification, and clot jamming. These strain-energy components are represented by a combination of simple harmonic oscillators, one-sided harmonic potentials, and a Gaussian potential. The proposed model, which is C0, C1, and C2 continuous with a total of 13 parameters, has been validated against three datasets: 1) fibrin clot in tension, 2) blood clot in compression, and 3) blood clots in shear, demonstrating its robustness. Subsequent simulations of a microscopic blood clot model are performed to uncover mechanistic correlations for a majority of the hyperelastic potential's stiffness/strain parameters. Our results show that only one proposed term concerning fiber buckling needs further refinement, while the remaining five strain-energy terms appear to describe precisely what they were intended to. In summary, the proposed model provides insight into the behavior of thromboembolisms and assistance in computer-aided design of surgical tools and interventions such as thrombectomy.

The influence of menopausal hormone therapy on somatic morbidity in postmenopausal women

Menopausal hormone therapy (MHT) which is initiated in women less than 60 years old or within 10 years after the onset of menopause for the relief of menopausal symptoms, treatment of urogenital syndrome or osteoporosis, is currently the only way to reduce the risk of developing cardiovascular diseases, thrombotic and metabolic disorders in healthy middle-aged women. This article presents the results of evaluating the use of hormone therapy in women during the menopausal transition to the state of somatic health in postmenopause by determining its effect on the state of the cardiovascular and bone systems, changes in the lipid profile, as well as on the risk of thrombosis in the postmenopause period.The objective: to determine the effect of MHT on somatic morbidity in postmenopausal women.Materials and methods. An analysis of the anamnesis, anthropometric indicators, results of general clinical and biochemical data of 120 women of menopausal age, who were divided depending on the use of menopausal hormone therapy into a study group (patients used MHT, n=60) and a control group (patients did not use MHT, n=60), is presented.All women were observed on the basis of the communal non-profit enterprise “Kyiv Perinatal Center” in the period from 2013 to 2023. Results. There was no significant difference in the indicators of the metabolic profile (levels of lipid fractions and glucose), as well as in anthropometric parameters (systolic and diastolic blood pressure, body mass index) between women of both groups (p>0.05). The risk of cardiovascular events (especially angina pectoris, hypertension) was higher in women of the control group who did not use hormonal drugs (related risk (RR) 0.5 with a 95% confidence interval (CI) from 0.28 to 0.91; p<0.007). However, it was found that there were significant differences between the groups in bone mineral density (the frequency of women with osteopenia was 43.3% in the control group versus 35% in the study group, and osteoporosis was diagnosed in 15% of women in the group without MHT versus 5% of women from the study group; RR is 0.69 with 95% CI≥0.5 at the confidence level p=0.05) and parameters affecting the risk of thrombotic complications (platelet level was 239.4±28.4×109/l in the control group versus 295.6±28.2×109/l in the study group, p<0.001; the level of fibrinogen was 7.7±1.2 mmol/l in women without MHT versus 8.7±2.0 mmol/l in women with MHT, p=0.001; prothrombin time was 13.2±1.3 sec in the control group versus 15.0±1.1 sec in the study group, p<0.001).Conclusions. Menopausal hormone therapy (MHT) is an effective method of preventing the development of osteopenic and osteoporotic conditions in women during the perimenopause period, but it also reliably significantly affects certain indicators of blood coagulation properties – the level of platelets, fibrinogen and prothrombin time – in the direction of their increase. It was established that the use of hormone replacement therapy the risks of developing adverse cardiovascular events (especially arterial hypertension and angina pectoris) are reduced, but, given the lack of difference between the compared groups of women in indicators of lipid metabolism, glucose, as well as in anthropometric data (which are the main risk factors for the development of cardiovascular diseases), further research is needed to establish the relationships of these parameters in more detail.During the appointment of MHT, one should be guided by the results of an individual risk/benefit assessment for the patient, paying special attention to the study of her anamnestic data.

Hemostasis Assessment in Neonates: Evaluation of Viscoelastic Properties of Blood Clots

Hemostasis Assessment in Neonates: Evaluation of Viscoelastic Properties of Blood Clots

Mechanical properties of clot made from human and bovine whole blood differ significantly

Thromboembolism – that is, clot formation and the subsequent fragmentation of clot – is a leading cause of death worldwide. Clots’ mechanical properties are critical determinants of both the embolization process and the pathophysiological consequences thereof. Thus, understanding and quantifying the mechanical properties of clots is important to our ability to treat and prevent thromboembolic disease. However, assessing these properties from in vivo clots is experimentally challenging. Therefore, we and others have turned to studying in vitro clot mimics instead. Unfortunately, there are significant discrepancies in the reported properties of these clot mimics, which have been hypothesized to arise from differences in experimental techniques and blood sources. The goal of our current work is therefore to compare the mechanical behavior of clots made from the two most common sources, human and bovine blood, using the same experimental techniques. To this end, we tested clots under pure shear with and without initial cracks, under cyclic loading, and under stress relaxation. Based on these data, we computed and compared stiffness, strength, work-to-rupture, fracture toughness, relaxation time constants, and prestrain. While clots from both sources behaved qualitatively similarly, they differed quantitatively in almost every metric. We also correlated each mechanical metric to measures of blood composition. Thereby, we traced this inter-species variability in clot mechanics back to significant differences in hematocrit, but not platelet count. Thus, our work suggests that the results of past studies that have used bovine blood to make in vitro mimics – without adjusting blood composition – should be interpreted carefully. Future studies about the mechanical properties of blood clots should focus on human blood alone.

Thromboelastographic evaluation of the effectiveness of choline or CDP-choline treatment on endotoxin-induced hemostatic alterations in dogs

Sepsis/endotoxemia associates with coagulation abnormalities. We showed previously that exogenous choline treatment reversed the changes in platelet count and function as well as prevented disseminated intravascular coagulation (DIC) in endotoxemic dogs. The aim of this follow-up study was to evaluate the effect of treatment with choline or cytidine-5′-diphosphocholine (CDP-choline), a choline donor, on endotoxin-induced hemostatic alterations using thromboelastography (TEG). Dogs were randomized to six groups and received intravenously (iv) saline, choline (20 mg/kg) or CDP-choline (70 mg/kg) in the control groups, whereas endotoxin (0.1 mg/kg, iv) was used alone or in combination with choline or CDP-choline at the same doses in the treatment groups. TEG variables including R- and K-time (clot formation), maximum amplitude (MA) and α-angle (clot stability), G value (clot elasticity), and EPL, A, and LY30 (fibrinolysis), as well as overall assessment of coagulation (coagulation index - CI), were measured before and at 0.5–48 h after the treatments. TEG parameters did not change significantly in the control groups, except for CI parameter after choline administration. Endotoxemia resulted in increased R-time and A value (P < 0.05), decreased K-time (P < 0.05), α-angle (P < 0.001) and CI values (P < 0.01) at different time points. Treatment with either choline or CDP-choline attenuated or prevented completely the alterations in TEG parameters in endotoxemic dogs with CDP-choline being more effective. These results confirm and extend the effectiveness of choline or CDP-choline in endotoxemia by further demonstrating their efficacy in attenuating or preventing the altered viscoelastic properties of blood clot measured by TEG.

Coagulant Protein-Free Blood Coagulation Using Catechol-Conjugated Adhesive Chitosan/Gelatin Double Layer.

Since the discovery of polyphenolic underwater adhesion in marine mussels, researchers strive to emulate this natural phenomenon in the development of adhesive hemostatic materials. In this study, bio-inspired hemostatic materials that lead to pseudo-active blood coagulation, utilizing traditionally passive polymer matrices of chitosan and gelatin are developed. The two-layer configuration, consisting of a thin, blood-clotting catechol-conjugated chitosan (CHI-C)layer and a thick, barrier-functioning gelatin (Geln) ad-layer, maximizes hemostatic capability and usability. The unique combination of coagulant protein-free condition with CHI-C showcases not only coagulopathy-independent blood clotting properties (efficacy) but also exceptional clinical potential, meeting all necessary biocompatibility evaluation (safety) without inclusion of conventional coagulation triggering proteins such as thrombin or fibrinogen. As a result, the CHI-C/Geln is approved by the Ministry of Food and Drug Safety (MFDS, Republic of Korea) as a class II medical device. Hemostatic efficacy observed in multiple animal models further demonstrates the superiority of CHI-C/Geln sponges in achieving quick hemostasis compared to standard treatments. This study not only enriches the growing body of research on mussel-inspired materials but also emphasizes the potential of biomimicry in developing advanced medical materials, contributing a promising avenue toward development of readily accessible and affordable hemostatic materials.

Blood Clot Dynamics and Fibrinolysis Impairment in Cancer: The Role of Plasma Histones and DNA.

Blood viscoelasticity and plasma protein levels can play an important role in the diagnosis and prognosis of cancer. However, the role of histones and DNA in modulating blood clot properties remains to be investigated. This study investigates the differences in blood viscoelasticity and plasma protein levels among cancer patients, individuals with other diseases, and healthy individuals. Blood samples were collected from 101 participants, including 45 cancer patients, 22 healthy individuals, and 34 individuals with other diseases. Rheological properties of clots formed in vitro by reconstituted elements of fibrinogen or plasma were analyzed with an Anton Paar Rheometer, USA. Plasma protein levels of D-dimer, TPA, EPCR, fibrinogen, and histone H3 were measured through ELISA. Blood clots were formed with or without DNA and histones (H3) by adding thrombin and calcium to plasma samples, and were evaluated for viscoelasticity, permeability, and degradation. Cancer patients show higher blood viscoelasticity and plasma D-dimer levels compared to healthy individuals and individuals with other diseases. Our in vitro analysis showed that the addition of histone to the plasma results in a significant decrease in viscoelasticity and mean fiber thickness of the clot formed thereafter. In parallel studies, using plasma from patients, DNA and histones were detected in fibrin clots and were associated with less degradation by t-PA. Moreover, our results show that the presence of DNA and histones not only increases clots' permeability, but also makes them more prone to degradation. Plasma histones and DNA affect the structure of the clot formed and induce defective fibrinolysis. Moreover, the increased viscoelastic properties of plasma from cancer patients can be used as potential biomarkers in cancer prognosis.

A mussel inspired polyvinyl alcohol/collagen/tannic acid bioadhesive for wet adhesion and hemostasis

Bioadhesives are useful in surgery for hemostasis, tissue sealing and wound healing. However, most bioadhesives have limitations such as weak adhesion in wet conditions, insufficient sealing and poor clotting performance. Inspired by the adhesion mechanism of marine mussels, a novel bioadhesive (PCT) was developed by simply combining polyvinyl alcohol (PVA), collagen (COL) and tannic acid (TA) together. The results showed that the adhesion, sealing and blood coagulation properties boosted with the increase of tannic acid content in PCT. The wet shear adhesion strength of PCT-5 (the weight ratio of PVA:COL:TA=1:1:5) was 60.8 ± 0.6 kPa, the burst pressure was 213.7 ± 0.7 mmHg, and the blood clotting index was 39.3% ± 0.6%, respectively. In rat heart hemostasis tests, PCT-5 stopped bleeding in 23.7 ± 3.2 s and reduced bleeding loss to 83.0 ± 19.1 mg, which outperformed the benchmarks of commercial gauze (53.3 ± 8.7 s and 483.0 ± 15.0 mg) and 3 M adhesive (Type No.1469SB, 35.3 ± 5.0 s and 264.0 ± 14.2 mg). The as-prepared bioadhesive could provide significant benefits for tissue sealing and hemorrhage control along its low cost and facile preparation process.

Titania nanotubes modified with copper enhance osteogenic differentiation of adipose derived stem cells.

To achieve long term success of orthopedic implants, it is critical to have a successful integration of bone and implant material. To accomplish this, various surface modifications have been investigated in research. Even though titania nanotubes and copper have individually demonstrated successful stem cell adhesion, proliferation and differentiation, these modifications have not yet been investigated together. In this study, we fabricated copper-modified titania nanotubes and evaluated the adhesion, proliferation and osteogenic differentiation of adipose derived stem cells on these surfaces. Implant surfaces also have to interact with blood after insertion in the body. Several studies have shown the importance of blood clots on material surfaces and their influence in differentiation of cells. Hence, blood clotting properties of modified surfaces were also investigated through whole blood clotting, and platelet adhesion and activation. The copper-modified titania nanotube surfaces demonstrated increased differentiation of adipose derived stem cells towards osteogenic lineage as well as enhanced blood clotting properties, thus they can be used as a potential surface for orthopedic implants.

Resonance, Velocity, Dispersion, and Attenuation of Ultrasound-Induced Shear Wave Propagation in Blood Clot In Vitro Models.

Improve the characterization of mechanical properties of blood clots. Parameters derived from shear wave (SW) velocity and SW amplitude spectra were determined for gel phantoms and in vitro blood clots. Homogeneous phantoms and phantoms with gel or blood clot inclusions of different diameters and mechanical properties were analyzed. SW amplitude spectra were used to observe resonant peaks. Parameters derived from those resonant peaks were related to mimicked blood clot properties. Three regions of interest were tested to analyze where resonances occurred the most. For blood experiments, 20 samples from different pigs were analyzed over time during a 110-minute coagulation period using the Young modulus, SW frequency dispersion, and SW attenuation. The mechanical resonance was manifested by an increase in the number of SW spectral peaks as the inclusion diameter was reduced (P < .001). In blood clot inclusions, the Young modulus increased over time during coagulation (P < .001). Descriptive spectral parameters (frequency peak, bandwidth, and distance between resonant peaks) were linearly correlated with clot elasticity values (P < .001) with R2 = .77 for the frequency peak, .60 for the bandwidth, and .48 for the distance between peaks. The SW dispersion and SW attenuation reflecting the viscous behavior of blood clots decreased over time (P < .001), mainly in the early stage of coagulation (first minutes). The confined soft inclusion configuration favored SW mechanical resonances potentially challenging the computation of spectral-based parameters, such as the SW attenuation. The impact of resonances can be reduced by properly selecting the region of interest for data analysis.

Blood Clots Are Mechanically Weak in Patients with Sickle Cell Disease

Introduction: Sickle cell disease (SCD) causes a hypercoagulable state characterized by frequent thrombotic sequelae including pulmonary embolism (PE) (Connes et al. Blood. Rev. 2016). Although the coagulation cascade is well characterized in SCD, the engineering-based, biomechanical structural properties of sickle blood clots are poorly understood. Furthermore, the role of clot mechanics in both traditional thrombotic disease manifestations (in situ blood clot, PE) but also common sickle cell related sequelae (pain, stroke) is unknown. Since blood clot embolization is inherently a mechanical process, where clots embolize or “fracture” when hemodynamic forces exceed the internal “strength” of the clot (Tutwiler et al. Sci. Adv. 2020), we submit that investigating the mechanical properties of sickle cell blood clots will reveal insights into the disease-specific factors at play. We hypothesize that SCD clots are not only structurally abnormal, but that this abnormality informs an increased propensity for clot embolization and causes severe vascular complications. Methods: Under the guidance and approval of the IRB, we acquired venipuncture-derived human blood samples from 10 healthy control subjects (14.3±0.9 g/dL Hgb) and 10 patients with sickle cell disease (7 HbSS, 2 HbSC, 1 HbS beta; 10.5±2.3 g/dL Hgb). We coagulated blood into 3D-printed molds designed for uniaxial extension on our mechanical testing machine, see figure 1. To do so, we added calcium chloride to a concentration of 20mM to reverse the ACD anticoagulant and incubated samples for 60 minutes at 37°C and atmospheric oxygen conditions (Sugerman et al. Curr. Protoc. 2021). Samples were then mounted to our tensile testing machine (Instron, Norwood, MA, USA) and two tests were conducted: extension-to-failure in a simple pure shear geometry and in a mode-I fracture geometry. From this data, we calculated various mechanical metrics by quantifying the structural abnormalities and propensity for embolization of SCD blood clots. Results and Conclusion: We primarily compared the stiffness and fracture toughness of sickle cell and healthy blood clots. Stiffness measures how the blood clot deforms in response to force, while fracture toughness measures whether a blood clot is strong or weak (i.e its resistance to rupture). The measured stiffness of SCD clots is 7.27±1.68 kPa, which is significantly higher than the stiffness of healthy clots, 5.22±1.09 kPa (p &amp;lt; 0.001). Additionally, the blood from SCD patients makes clots with a fracture toughness of 2.91±0.85 J/m 2, which is significantly lower than the fracture toughness of healthy clots, 4.43±1.11 J/m 2 (p &amp;lt; 0.0001), see figure 2. The high stiffness of sickle cell blood clots suggests that they are more resistant to deformation than healthy clots. However, the low fracture toughness of sickle cell blood clots suggests that they are more likely to break or embolize when compared to healthy clots. In other words, sickle blood clots exhibit mechanical properties similar to ceramic which has high stiffness and low toughness as opposed to leather (low stiffness, high toughness) or diamond (high stiffness, high toughness). In conclusion, our biomechanical findings of higher stiffness and lower toughness in sickle blood clots are well aligned with established rheological data showing that SCD red blood cells are less deformable than healthy red blood cells (Lu et al. Exp. Biol. Med. 2020). That is, the low deformability of red blood cells in SCD is apparent even at the clot level, which may inform novel disease mechanisms. The sickle cell related determinants of these biomechanical abnormalities, their role in clinical outcomes (PE, pain and stroke) and their response to therapy is the object of future study.

Mechanobiology of Megakaryocyte-Driven Contraction of Plasma Clots

Background: Contractility of non-muscle cells plays a crucial role in various cellular processes including motility, morphogenesis, division, genome replication, intracellular transport, and secretion. Platelet-induced blood clot contraction is an essential process which plays a role in preventing bleeding and in thrombotic disorders. Megakaryocytes (MKs), which are the precursor cells of platelets, share many proteins and structures with platelets. However, little is known about the ability of MKs to contract and interact with extracellular matrix proteins such as fibrin. Previously, the non-muscle myosin II contractility was shown to be essential for MK migration within the bone marrow, to avoid premature proplatelet formation, and to allow branching of proplatelets. Recent studies have identified MKs in lung and brain tissues, as well as associated with thrombi in deceased COVID-19 patients. Notably, patients with severe COVID-19 exhibit elevated MK counts in their blood, indicating potential involvement in hemostasis and thrombosis. Nevertheless, the specific mechanisms by which MKs can contribute to clot contraction remain unknown. Methods: Human induced pluripotent stem cells (iPSC) were differentiated into HPCs followed by expansion to megakaryocytes (iMKs) and analyzed by flowcytometry. Clot formation and contraction were initiated by adding thrombin and calcium to platelet-free-plasma with resuspended iMKs. A combination of real-time macroscale optical tracking, high-resolution confocal microscopy and biomechanical measurements were applied to elucidate the contractile cellular mechanisms and mechanotransduction pathways in iMKs, and ultimately comparing them with platelets. Results: Flowcytometry analysis of unstimulated and thrombin-stimulated iMKs revealed that the major fraction of unstimulated cells expressed αIIbβ3 and GPIbα (~78%), but did not bind PAC-1, a monoclonal antibody specific for the activated conformation of αIIbβ3. Stimulation of iMKs with 1U/ml of thrombin resulted in PAC-1 binding (~68%), indicating activation of aIIbb3. The optical tracking of clot size change over time revealed that thrombin-stimulated iMKs were able to shrink macroscopic plasma clots with biphasic kinetics, similar to platelets. iMK-containing clots and platelet-reach-plasma clots equalized by the total cell surface area demonstrated comparable contraction rates and extent of contraction. The average maximal contractile force per individual iMK in the clot was found to be 145±98nN. In the presence of blebbistatin, the mean final extent and velocity of clot contraction of iMK-containing clots reduced in a dose-dependent manner, in comparison to untreated clots. Pretreatment of iMKs with 1μM latrunculin A, an inhibitor of actin polymerization, completely prevented contraction of plasma clots. In addition, contraction of plasma clots by activated iMKs was abrogated by 10μg/ml abciximab, that prevented binding of fibrin(ogen) to integrin a IIbb 3 receptors. The structural mechanisms of iMK contractility involved formation of filopodia and larger cytoplasmic protrusions undergoing extension-retraction cycles after being attached to surrounding fibrin fibers. Contraction of iMKs caused remodeling of the extracellular fibrin matrix by inducing spatial reorientation of fibrin fibers, accumulation of the fibrin mass on the iMK surface, and compaction of the entire fibrin network. Conclusions: We have demonstrated a hitherto unknown ability of individual MKs to shrink fibrin clots and deciphered the cellular mechanisms of contractility of iPSC-derived MKs. The molecular mechanisms of MK-driven fibrin clot shrinkage were shown to be similar or identical to those of activated platelets, involving non-muscle myosin II activity, actin polymerization, and integrin αIIbβ3-fibrin interactions. Our findings provide a novel mechanistic insight into mechanobiology of MKs that may play a role in modulating the properties of hemostatic blood clots and thrombi. In addition, iMKs can be used as model cells with a potential of genetic modifications to study platelet structure and function, including their contractility.

Coagulation Properties of Blood in Healthy University Students in Port Harcourt

Despite the fact that the World Health Organization (WHO) had provided an average global reference data of Coagulation Properties (CP) of blood in the world, available statistics still suggest a significant discrepancy in CPs of blood among various age groups, socioeconomic classes and races in different locations of the world. Here in Port Harcourt Nigeria, absence of such local reference data had continued to pose over-reliance on the WHO global standards without recourse to our distinctive geospatial and socioeconomic peculiarities. As a result, this study therefore investigated coagulation properties of blood in healthy university students in Port Harcourt. A total of 157 participants were recruited into the study using Stratified Random Sampling techniques. They were administered well-structured questionnaires for an on-the-spot data collections. Thereafter, 5ml of venous blood were aspirated for various coagulation properties (Bleeding, clotting and Prothrombin times and Platelets Counts) investigation. Clotting and bleeding times were measured instantly using capillary and Ivy’s methods respectively. Results from the study revealed a significant (ρ≤0.05) coagulation difference between the WHO standards and both gender (male, 311032 ± 17300* and female, 293600 ± 12800*) for platelets counts. In the age groups, only ≥40 group were significant to all CP (10.30 ± 0.00* for BT, 10.00 ± 1.30* for CT, 10.22 ± 2.88* for PT and 190320.73 ± 1886.45* for PC). Similar significant result was also noted for Obese Class 2, morbid obesity and protein diet groups as compared with the Control. This study therefore concluded that CP significantly vary with the WHO standards, age, gender, BMI and nutritional background and recommended similar study be conducted in other locations in Nigeria and Africa.

Bioinspired Natural Shellac Dressing for Rapid Wound Sealing and Healing.

Developing safe and effective wound dressings that address the complexities of wound healing is an ongoing goal in biomaterials research. Inspired by the shield used to protect lac insects, we have designed and developed a type of bioactive shellac-based wound dressing in this paper. The dressing exhibited a high adhesion energy of 146.6 J·m-2 in porcine skin and showed a reversible binding due to its pH sensitivity. Meanwhile, a novel "shellac-like" compound, n-octacosanol gallate ester, has been synthesized and added to the dressing to improve its antibacterial and blood coagulation properties. The novel shellac-based dressing could be sprayed to form a sticky film within 70 s for rapid hemostasis and wound sealing, which could be conveniently applied to various wounds on extensible body parts. In addition, the shellac-based dressing can actively promote the healing of a full-thickness wound in the skin of mice. We also used molecular dynamics simulations to investigate the interactions between the shellac molecule and the phospholipid bilayer and attempted to show that the shellac molecule was beneficial for wound healing. This work provides a novel and practical bioinspired wound dressing with significant properties, facile preparation, and ease of use, which is an interesting alternative to its traditional counterparts.

A self-healable and bioadhesive acacia gum polysaccharide-based injectable hydrogel for wound healing acceleration.

The present study aimed at developing an injectable hydrogel based on acacia gum (AG) for wound healing acceleration. The hydrogels were synthetized through metal-ligand coordination mediated by Fe3+ and characterized in terms of gelation time, gel content, initial water content, swelling capacity, water retention ratio, and porosity. Moreover, FTIR, XRD and TGA analyses were performed for the hydrogels and allantoin (Alla) loaded ones. Furthermore, bioadhessiveness, and self-healing as well as antibacterial, toxicity and wound healing potentials of the hydrogels were evaluated. The hydrogels displayed fast gelation time, high swelling, porosity, and bioadhessiveness, as well as antioxidant, self-healing, antibacterial, blood clotting, and injectability properties. FTIR, XRD and TGA analyses confirmed hydrogel synthesis and drug loading. The Alla-loaded hydrogels accelerated wound healing by decreasing the inflammation and increasing the cell proliferation as well as collagen deposition. Hemocompatibility, cell cytotoxicity, and in vivo toxicity experiments were indicative of a high biocompatibility level for the hydrogels. Given the advantages of fast gelation, injectability and beneficial biological properties, the use of Alla-loaded hydrogels could be considered a new remedy for efficient wound healing.

Probing interactions of red blood cells and contracting fibrin platelet clots

Contraction of blood clots plays an important role in blood clotting, a natural process that restores hemostasis and regulates thrombosis in the body. Upon injury, a chain of events culminate in the formation of a soft plug of cells and fibrin fibers attaching to wound edges. Platelets become activated and apply contractile forces to shrink the overall clot size, modify clot structure, and mechanically stabilize the clot. Impaired blood clot contraction results in unhealthy volumetric, mechanical, and structural properties of blood clots associated with a range of severe medical conditions for patients with bleeding and thrombotic disorders. Due to the inherent mechanical complexity of blood clots and a confluence of multiple interdependent factors governing clot contraction, the mechanics and dynamics of clot contraction and the interactions with red blood cells (RBCs) remain elusive. Using an experimentally informed, physics-based mesoscale computational model, we probe the dynamic interactions among platelets, fibrin polymers, and RBCs, and examine the properties of contracted blood clots. Our simulations confirm that RBCs strongly affect clot contraction. We find that RBC retention and compaction in thrombi can be solely a result of mechanistic contraction of fibrin mesh due to platelet activity. Retention of RBCs hinders clot contraction and reduces clot contractility. Expulsion of RBCs located closer to clot outer surface results in the development of a dense fibrin shell in thrombus clots commonly observed in experiments. Our simulations identify the essential parameters and interactions that control blood clot contraction process, highlighting its dependence on platelet concentration and the initial clot size. Furthermore, our computational model can serve as a useful tool in clinically relevant studies of hemostasis and thrombosis disorders, and post thrombotic clot lysis, deformation, and breaking.

Elasticity of whole blood clots measured via Volume Controlled Cavity Expansion

Measuring and understanding the mechanical properties of blood clots can provide insights into disease progression and the effectiveness of potential treatments. However, several limitations hinder the use of standard mechanical testing methods to measure the response of soft biological tissues, like blood clots. These tissues can be difficult to mount, and are inhomogeneous, irregular in shape, scarce, and valuable. To remedy this, we employ in this work Volume Controlled Cavity Expansion (VCCE), a technique that was recently developed, to measure local mechanical properties of soft materials in their natural environment. Through highly controlled volume expansion of a water bubble at the tip of an injection needle, paired with simultaneous measurement of the resisting pressure, we obtain a local signature of whole blood clot mechanical response. Comparing this data with predictive theoretical models, we find that a 1-term Ogden model is sufficient to capture the nonlinear elastic response observed in our experiments and produces shear modulus values that are comparable to values reported in the literature. Moreover, we find that bovine whole blood stored at 4 °C for greater than 2 days exhibits a statistically significant shift in the shear modulus from 2.53 ± 0.44 kPa on day 2 (N = 13) to 1.23 ± 0.18 kPa on day 3 (N = 14). In contrast to previously reported results, our samples did not exhibit viscoelastic rate sensitivity within strain rates ranging from 0.22 – 21.1 s−1. By surveying existing data on whole blood clots for comparison, we show that this technique provides highly repeatable and reliable results, hence we propose the more widespread adoption of VCCE as a path forward to building a better understanding of the mechanics of soft biological materials.

Rapid microfluidic-thromboelastography (μ-TEG) for evaluating whole blood coagulation and fibrinolysis at elevated shear rates

The assessment of hemostasis and fibrinolysis is essential in emergency settings to make timely medical decisions. While conventional thromboelastography (TEG) analyzers provide comprehensive information on blood clotting, their long test times are often unsuitable for emergency patients. In this study, we propose an innovative method of microfluidic thromboelastography (μ-TEG) that rapidly measures the viscoelastic properties of blood coagulation in oscillating flow through circular tubes. Our μ-TEG system moves a blood sample back and forth through a circular tube subjected to sinusoidal pressure, generating shear rates ranging from 1.2 to 20 s−1, higher than those of conventional TEGs. The movements are monitored by a pressure sensor and converted to a conventional TEG. Key parameters such as MA and Ly30 can be acquired within 10–12 min for normal samples. Our study showed that the increased shear rate in the μ-TEG system alters the coagulation mechanism, resulting in increased coagulation strength and rapid fibrinolysis. Despite the short test time, the μ-TEG showed good agreement with the TEG5000. The rapid measurement of μ-TEG makes it a useful tool for analyzing hemostasis and fibrinolysis in emergency and operating rooms.

Systematic mapping of the conformational landscape and dynamism of soluble fibrinogen

BackgroundFibrinogen is a soluble, multisubunit, and multidomain dimeric protein, which, upon its proteolytic cleavage by thrombin, is converted to insoluble fibrin, initiating polymerization that substantially contributes to clot growth. Fibrinogen contains numerous, transiently accessible “cryptic” epitopes for hemostatic and immunologic proteins, suggesting that fibrinogen exhibits conformational flexibility, which may play functional roles in its temporal and spatial interactions. Hitherto, there have been limited integrative approaches characterizing the solution structure and internal flexibility of fibrinogen. MethodsHere, utilizing a multipronged, biophysical approach involving 2 solution-based techniques, temperature-dependent hydrogen-deuterium exchange mass spectrometry and small angle X-ray scattering, corroborated by negative stain electron microscopy, we present a holistic, conformationally dynamic model of human fibrinogen in solution. ResultsOur data reveal 4 major and distinct conformations of fibrinogen accommodated by a high degree of internal protein flexibility along its central scaffold. We propose that the fibrinogen structure in the solution consists of a complex, conformational landscape with multiple local minima. This is further supported by the location of numerous point mutations that are linked to dysfibrinogenemia and posttranslational modifications, residing near the identified fibrinogen flexions. ConclusionThis work provides a molecular basis for the structural “dynamism” of fibrinogen that is expected to influence the broad swath of its functionally diverse macromolecular interactions and fine-tune the structural and mechanical properties of blood clots.