Elastin Fibers Research Articles

Comprehensive analyses and prioritization of various swim bladder-derived extracellular matrix in the application of heart valve prosthesis

Calcification-caused failure and deterioration have become the biggest issues facing traditional biological heart valves (BHVs). Thus, developing new source of materials with the ability to resist calcification is an imperative demand of clinical. In our previous work, swim bladder was proved with superb calcification-resistance as a promising candidate for cardiovascular biomaterials. To find the optimal choice of swim bladder, we herein further investigated four types of swim bladders including grass carp (GC), culter alburnus (CA), carp (C) and silver carp (SC) as material source of the BHVs. Data showed that all the swim bladder was mainly composed of elastin fiber, collagen fiber and glycosaminoglycan (GAG). All the groups except GC group can meet the basic mechanical and materials stability requirements as BHVs. Moreover, the calcification of swim bladder derived from SC was proved significantly lower than that of CA and C groups with in vivo rat subcutaneous implantation model. Additionally, in vitro assays demonstrated that four types of swim bladder exhibited well hemocompatibility and cytocompatibility. Collectively, the superior properties including low calcification, adequate mechanical, high stability, as well as excellent hemocompatibility and cytocompatibility of SC-derived swim bladder endow it great competence as BHVs.

Revealing the elasticity of an individual aortic fiber during ageing at nanoscale by in situ atomic force microscopy.

Arterial stiffness is a complex process affecting the aortic tree that significantly contributes to cardiovascular diseases (systolic hypertension, coronary artery disease, heart failure or stroke). This process involves a large extracellular matrix remodeling mainly associated with elastin content decrease and collagen content increase. Additionally, various chemical modifications that accumulate with ageing have been shown to affect long-lived assemblies, such as elastic fibers, that could affect their elasticity. To precisely characterize the fiber changes and the evolution of its elasticity with ageing, high resolution and multimodal techniques are needed for precise insight into the behavior of a single fiber and its surrounding medium. In this study, the latest developments in atomic force microscopy and the related nanomechanical modes are used to investigate the evolution and in a near-physiological environment, the morphology and elasticity of aorta cross sections obtained from mice of different ages with an unprecedented resolution. In correlation with more classical approaches such as pulse wave velocity and fluorescence imaging, we demonstrate that the relative Young's moduli of elastic fibers, as well as those of the surrounding areas, significantly increase with ageing. This nanoscale characterization presents a new view on the stiffness process, showing that, besides the elastin and collagen content changes, elasticity is impaired at the molecular level, allowing a deeper understanding of the ageing process. Such nanomechanical AFM measurements of mouse tissue could easily be applied to studies of diseases in which elastic fibers suffer pathologies such as atherosclerosis and diabetes, where the precise quantification of fiber elasticity could better follow the fiber remodeling and predict plaque rupture.

The Dynamics of Hydrated Proteins Are the Same as Those of Highly Asymmetric Mixtures of Two Glass-Formers.

Customarily, the studies of dynamics of hydrated proteins are focused on the fast hydration water ν-relaxation, the slow structural α-relaxation responsible for a single glass transition, and the protein dynamic transition (PDT). Guided by the analogy with the dynamics of highly asymmetric mixtures of molecular glass-formers, we explore the possibility that the dynamics of hydrated proteins are richer than presently known. By providing neutron scattering, dielectric relaxation, calorimetry, and deuteron NMR data in two hydrated globular proteins, myoglobin and BSA, and the fibrous elastin, we show the presence of two structural α-relaxations, α1 and α2, and the hydration water ν-relaxation, all coupled together with interconnecting properties. There are two glass transition temperatures Tgα1and Tgα2 corresponding to vitrification of the α1 and α2 processes. Relaxation time τα2(T) of the α2-relaxation changes its Arrhenius temperature dependence to super-Arrhenius on crossing Tgα1 from below. The ν-relaxation responds to the two vitrifications by changing the T-dependence of its relaxation time τν(T) on crossing consecutively Tgα2 and Tgα1. It generates the PDT at Td where τν(Td) matches about five times the experimental instrument timescale τexp, provided that Td > Tgα1. This condition is satisfied by the hydrated globular proteins considered in this paper, and the ν-relaxation is in the liquid state with τν(T) having the super-Arrhenius temperature dependence. However, if Td < Tgα1, the ν-relaxation fails to generate the PDT because it is in the glassy state and τν(T) has Arrhenius T-dependence, as in the case of hydrated elastin. Overall, the dynamics of hydrated proteins are the same as the dynamics of highly asymmetric mixtures of glass-formers. The results from this study have expanded the knowledge of the dynamic processes and their properties in hydrated proteins, and impact on research in this area is expected.

Transdermal redermalization in rosacea: Rehab procedures in intercurrent period

Background: The authors presented their own experiences of skin restoration in patients with rosacea after a course of active therapy using transdermal redermalization.&#x0D; Aim: The course of cosmetic correction procedures using this method aimed to restore the energy potential of cells, water balance, and structures of the dermal elastin fibers, normalize microcirculation processes, and create an optimal physiological environment for the mitotic activity of epidermal cells.&#x0D; Materials and methods: An innovative method of transdermal redermalization represents the administration of a drug containing hyaluronic acid and sodium succinate using the technique of papular intradermal injections, taking into account the peculiarities of lymphatic drainage in the facial area.&#x0D; Results: To assess the therapys efficiency, noninvasive monitoring of changes in morphological structures of the skin was performed using confocal laser scanning microscopy.&#x0D; Conclusions: The authors revealed the high efficiency of the method, which controls the remission state for a long term, subsequently avoiding drug therapy

New approaches to skin photodamage histology-Differentiating 'good' versus 'bad' Elastin.

BackgroundPhotodamage creates changes within the skin layers known as solar elastosis. This presents as fragmentation of collagen and elastin fibers, decreases in the extracellular matrix (ECM) ground substance, as well as hyaluronic acid decrease in the thinning epidermis. Traditional immunohistochemistry (IHC) staining has failed to differentiate degenerated elastin from new elastin fibers generated with various topical strategies.AimsA combination of stains that can offer a regenerative narrative distinguishing newly formed collagen and elastin from that of degenerated protein, thus distinguishing “good” vs “bad” elastin.MethodsA series of stains were explored based on their ability to identify early regenerative changes within epidermal, dermal, and ECM areas to examine consistency of outcomes and reliability.ResultsA combination of Movat, fibrillin, elafin, and versican for elastogenesis and reversal of solar elastosis. CD44 for HA status (mainly epidermal) and Herovici stain for identifying early collagenesis in the ECM provides a comprehensive range of stains for identifying new elastin and collagenConclusionThis suggested stain combination appears to offer an ideal collection of stains for identifying regenerative events within the skin layers.

Lysyl oxidase inhibition in primary myelofibrosis: A renewed strategy.

Primary myelofibrosis (PMF) is a type of myeloproliferative neoplasm (MPN) that portends a poor prognosis and has limited options for treatment. PMF is often driven by clonal mutations in one of three genes that regulate the JAK-STAT signaling pathway, leading to hyperactivation of this signaling pathway and over-proliferation of megakaryocytes (MKs) and their precursors. PMF presents with debilitating symptoms such as splenomegaly and weight loss. The few available treatments for PMF include a JAK2 inhibitor, ruxolitinib, which causes side effects and is not always effective. The extracellular matrix (ECM) and bone marrow (BM) microenvironment may play an important role in the pathogenesis of PMF. Lysyl oxidase (LOX), an enzyme that plays a key role in the ECM by facilitating the cross-linking of collagen and elastin fibers, has been shown to be upregulated in MKs of PMF mice and in PMF patients, suggesting its role in the progression of BM fibrosis. Recently, LOX has been identified as a potential novel therapeutic target for PMF and the development of new small molecule LOX inhibitors, PXS-LOX_1 and PXS-LOX_2, has shown some promise in slowing the progression of PMF in pre-clinical studies. Given that these inhibitors displayed an ability to target the dysregulation of the ECM via LOX inhibition, they show promise as therapeutic agents for an underappreciated aspect of PMF.

Glucocorticoid-Induced Skin Atrophy: The Old and the New.

Glucocorticoids are major therapeutic agents highly used in the medical field. Topical glucocorticoids have biologic activities which make them useful in dermatology – anti-inflammatory, vasoconstrictive, immune suppressive and antiproliferative, in treating inflammatory skin disorders (allergic contact eczema, atopic hand eczema, nummular eczema, psoriasis vulgaris or toxic-irritative eczema). Unfortunately, the beneficial effects of topical glucocorticoids are shadowed by their potential for adverse effects – muscle or skin atrophy, striae distensae, rubeosis or acne. Skin atrophy is one of the most prevalent side-effects, with changes found in all skin compartments – marked hypoplasia, elasticity loss with tearing, increased fragility, telangiectasia, bruising, cutaneous transparency, or a dysfunctional skin barrier. The structure and function of the epidermis is altered even in the short-term topical glucocorticoid treatment; it affects stratum corneum components, subsequently affecting skin barrier integrity. The dermis is altered by directly inhibiting fibroblast proliferation, reducing mast cell numbers, and loss of support; there is depletion of mucopolysaccharides, elastin fibers, matrix metalloproteases and inhibition of collagen synthesis. Atrophogenic changes can be found also in hair follicles, sebaceous glands or dermal adipose tissue. Attention should be paid to topical glucocorticoid treatment prescription, to the beneficial/adverse effects ratio of the chosen agent, and studies should be oriented on the development of newer, innovative targeted (gene or receptor) therapies.

&lt;p&gt;A Novel Splice-Site Mutation in the &lt;em&gt;ELN&lt;/em&gt; Gene Suggests an Alternative Mechanism for Vascular Elastinopathies&lt;/p&gt;

The ELN gene encodes elastin, a fundamental protein of the extracellular matrix that confers elasticity to different tissues including blood vessels. The formation of elastin fibers is a complex process involving monomer coacervation and subsequent crosslinking. Mutations in exons 1–29 of the ELN gene have been linked to supravalvular aortic stenosis (SVAS) whereas mutations in exons 30–33 are associated with autosomal dominant cutis laxa (ADCL). This striking segregation has led to the hypothesis that distinct molecular mechanisms underlie both diseases. SVAS is believed to arise through haploinsufficiency while ADCL is hypothesized to be caused by a dominant negative effect. Here, we describe a patient with SVAS harboring a novel splice-site mutation in the last exon of ELN. The location of this mutation is not consistent with current knowledge of SVAS, since all mutations reported in the C-terminus have been found in ADCL patients, and a thorough evaluation did not reveal significant skin involvement in this case. RT-PCR analysis of skin tissue showed that C-terminal mutations in the region can lead to the production of aberrant transcripts through intron retention and activation of cryptic splice sites and suggest that disruption of the very last exon can lead to functional haploinsufficiency potentially related to SVAS.

Abstract 14780: Developing a Model for Abdominal Aortic Aneurysm in Swine

Introduction: Abdominal aortic aneurysms (AAA) are responsible for over 150,000 deaths worldwide annually. Attempts at producing a reliable large-animal model of AAA have proven challenging. We sought to create a reproducible swine model of AAA using enzymatic degradation of the aortic wall. Methods: A total of 9 male Yorkshire swine received periadventitial injections of type 1 collagenase (23.5 mg) and porcine pancreatic elastase (500 mg) into a 4 cm segment of infrarenal aorta. Aortic diameter growth was monitored at POD 7 and 14 using ultrasound. The animals were euthanized on POD 21, and the suprarenal (control) and infrarenal (treated) aorta was harvested for analysis, after gross measurement of aortic diameter under physiologic blood pressure. Sections of control and treated aorta were used to obtain tensile strength using a tensiometer. Additional segments of the aorta were collected for histopathological analysis (H&amp;E, elastin, alpha smooth muscle actin). PCR of matrix metalloproteinases (MMP9) was conducted. Groups were compared with paired t-tests, or ANOVA for repeated measures, where appropriate. Results: Average percent growth of aortic diameter at POD 21 for treated segments was 27% +/- 16.5% versus 4.5% +/- 4% for control tissue. The average difference in aortic growth by subject, was 26.7% [14.6%-38.8%]; (p&lt;0.001). Aortic medial thickness was decreased in treated tissue; 235 um +/- 208 um versus 645 um +/- 191 um (p&lt;0.0001). Quantity of both medial elastin fibers, and vascular smooth muscles cells was decreased in treated tissue; 1.8% +/- 3.16%, compared to 9.9% +/- 6.85% (p&lt;0.0001), and 24% +/- 6.8% versus 37.4% +/- 6.9%, respectively. Tensile strength was also decreased in treated tissue; 16.7 MPa +/- 7 MPa versus 29.5 MPa +/- 10.7 MPa (p=0.0002). A 12-fold increase in expression of MMP9 mRNA was also demonstrated in aneurysmal tissue (p=0.002) Conclusion: A reproducible, large-animal model of AAA, with anatomical, histopathological, and biomechanical properties that are clinically translatable, can be achieved with extraluminal enzymatic degradation.

The Effects of Subcutaneously Injected Novel Biphasic Cross-Linked Hyaluronic Acid Filler: In Vivo Study.

Biphasic hyaluronic acid (HA) fillers have been used extensively to improve facial skin. However, in some cases, the skin surface is irregular because of the premature loss of HA solution. We propose a new biphasic filler (G-filler) to overcome this problem by using small particles of HA hydrogel instead of HA solution, which can provide a smooth skin surface and good durability. We evaluated the rheologic properties of G-filler and its physiologic effects after subcutaneous injection in a mouse model by histologic analysis. The G-filler showed a similar elastic modulus (G') and complex viscosity (η*) as the conventional biphasic filler, but had a higher viscous modulus (G″) than the conventional monophasic filler. The highest material elasticity (tan δ) value and the lowest percentage elasticity value indicate the rheologic properties of G-filler are closer to those of liquids. After subcutaneous injection of G-filler, collagen content (~ 2-fold) and elastin fibers (~ 6.5-fold) were significantly increased at 12weeks compared to those of the saline group. Fibronectin (~ 2.6-fold) and the laminin-immunolabeled cell number (~ 6-fold) were also significantly increased at 12weeks. Significant increases in the CD31-immunoreactive cell numbers of the G-filler groups were observed at 2, 6, and 12weeks (~ 3.7-fold) compared to those of the saline groups. There were no significant differences between the G-filler and saline groups in patterns of skin thickness and inflammatory cell numbers around loading sites. These findings demonstrate that the injection of a new biphasic filler with improved rheologic properties can effectively stimulate extracellular matrix production and angiogenesis without safety concerns. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors - www.springer.com/00266 .

Desarrollo, elaboración y control de un preparado cosmético antiestrías

Las estrías son cicatrices atróficas formadas por la rotura y pérdida de fibras de colágeno, elastina y fibrina. Actualmente, se han convertido en un problema estético más que médico, que cursan con un gran componente emocional, y que pueden ocasionar síntomas físicos como picazón, sensibilidad y dolor. Se pueden desarrollar a cualquier edad, pero son más frecuentes en el inicio de la pubertad; son más frecuentes en las mujeres y se desarrollan en zonas de crecimiento corporal. Las estrías están condicionadas por múltiples factores endocrinos y exocrinos.&#x0D; A día de hoy, no existe un tratamiento que elimine por completo a la estría, por lo que se emplean tratamientos orientados a la prevención y atenuacion de la misma. El objetivo de esta memoria es el desarrollo de productos cosméticos con una composición eficaz, combinables con otros tratamientos y de fácil elaboración desde la oficina de farmacia.

Novel Recombinant Tropoelastin Implants Restore Skin Extracellular Matrix

Elastin is an essential component of the dermis, providing skin with elasticity and integrity. Elastin and other dermal components are gradually lost through aging, sun damage, and following injury, highlighting a need to replace these components to repair the skin. Tropoelastin (TE) in monomeric form was previously shown to be utilized as a substrate by dermal fibroblasts during the production of elastin fibers in vitro. To analyze coaccumulation of elastin and collagen and gene expression of biomarkers associated with elastin production, examine the ex vivo effects of recombinant human TE (rhTE) and hyaluronic acid (HA) on epidermal and dermal structures, and evaluate the in vivo response following intradermal injections of rhTE and HA. Human dermal fibroblasts and 3-D skin patch models were cultured for in vitro analysis. Ex vivo analysis was performed using skin explants. In vivo studies were done in 6-week-old male CD Hairless rats. Different formulations of rhTE, soluble or crosslinked using derivatized HA (dHA), were tested and analyzed. rhTE in monomeric form was utilized as a substrate by dermal fibroblasts during the production of branched elastin and fibrous collagen networks in vitro. Formulations of rhTE crosslinked with dHA demonstrated increased expression of hyaluronic acid synthase 1 and ex vivo results revealed increased moisture content and glycosaminoglycan (GAG) deposition versus dermal filler control. Intradermal rhTE‒dHA injection produced colocalized human‒rat elastin fibers in vivo. These results suggest that the novel rhTE‒dHA matrix is an attractive material to support skin tissue repair.J Drugs Dermatol. 2020;19(12): doi:10.36849/JDD.2020.5375.

Activated adaptive immune system in dissected bicuspid aortic valve aortas: trigger for dissection?

Abstract Background/Introduction Bicuspid aortic valve (BAV) is associated with ascending aorta aneurysms and dissections. Presently, genetic factors and pathological flow patterns are considered responsible for aneurysm formation in BAV. Despite, indication for preventive surgery is presently only defined by vessel diameter which is poor marker for dissection, as it does not take other processes responsible for the vulnerability of the aorta into account. Purpose Inflammation is not considered a player in BAV aortopathy. We introduce a quantitative immunohistochemistry (IHC) approach to sensitively look at the potential role of both the innate and adaptive immune system in BAV aortopathy. Methods Dilated (n=8), non-dilated (n=14) and dissected (n=4) BAV ascending aortas were collected during surgery or from post-mortem donors. Median time from symptoms to surgery for dissections was just over 4 hours. Tissue was stained with a novel 8-colour IHC technique allowing for simultaneous visualization of 6 markers per slide, completed with DAPI nuclear counter-stain and elastin fiber autofluorescence. One panel focused on the adaptive immune system (identifying B cells and classic dendritic cells type 2 (cDC2s) and phenotyping T cells), and the other on the innate immune system (assessing macrophage polarization and neutrophil extravasation). All cells were identified and comprehensively phenotyped using automated quantitative analysis. Results Aneurysm formation was associated with an organized and consistent increase of lymphocytes in the adventitia. B cell follicles and helper T cell expansion were identified, suggestive of a targeted adaptive immune response (Fig. 1a). Only dissected aortas showed a statistically significant increase of helper T (p=0.3) and cDC2s (p=0.3) in the media, when compared to non-dilated and dilated samples (Fig. 1b). The short time between dissection symptoms and surgery suggests these cells were present before the dissection occurred. Furthermore, aneurysms and dissections are associated with a shift in macrophage phenotype to the more aggressive M1-like subset. In summary, we found that a progression of aggressive immune cells in the adventitia and media was correlated to a progression in disease state; from normal to dilated to dissected. Conclusions Aorta dilatation in patients with BAV is associated with an expansion of B and helper T cells in the adventitial compartment without changes in the media. This result might indicate an antigen-driven adaptive immune response. Only dissections show an increase in helper T cells and cDC2s in the media, together with polarization of macrophages to a more M1-like phenotype. We hypothesize that antigen-specific helper T cells expand in the adventitia, migrate to the media, and then potentiate macrophages which can eventually lead to tissue degeneration. These associations could shine light on the final step in the deterioration of the aorta towards a dissection. Figure 1. Microscopy results Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): TTW-NWO open technology grant (STW-14716), ERC-2014-StG-336454-CoNQUeST

Cutaneous Elastorrhexis; A Heralding Sign of Gronblad-Strandberg Syndrome: A Case Report

Introduction: Pseudoxanthoma Elasticum (PXE), also called Gronblad-Strandberg syndrome, is an autosomal recessive disorder due to mutation in the ABCC6 allele on chromosome 16p. It is characterized by the progressive fragmentation and calcification of elastin fibers of the dermis, blood vessels, and Bruch’s membrane of the eye. In this article, the authors present a case of PXE with cutaneous elastorrhexis. Case Presentation: A 31-year-old female presented with skin changes in the form of yellowish linearly arranged papules over the lateral side of the neck and anterior abdomen since adolescence. Her retinoscopy and cardiovascular examinations were reported as normal. The molecular analysis could not be done due to financial limitations. Based on these findings, the patient was suspected of PXE according to the revised criteria for the diagnosis of PXE. Conclusions: Skin lesions are generally first to appear in adolescence. Ocular findings develop at later ages, i.e., third or fourth decades. Cardiovascular manifestations develop later in life. Hence, skin changes can aid in the early diagnosis of PXE and help clinicians to screen patients for systemic complications. Being a multisystem heritable disorder with morbidity and mortality, there is a need to formulate the clinical criteria for definitive diagnosis in resource-poor settings where molecular assays cannot be performed. The recognition of typical skin lesions can aid in the accurate diagnosis to facilitate the early detection and management of life-threatening systemic complications.

Imaging of muscle activity-induced morphometric changes in fibril network of myofascia by two-photon microscopy.

Myofascia, deep fascia enveloping skeletal muscles, consists of abundant collagen and elastin fibres that play a key role in the transmission of muscular forces. However, understanding of biomechanical dynamics in myofascia remains very limited due to less quantitative and relevant approaches for in vivo examination. The purpose of this study was to evaluate the myofascial fibril structure by means of a quantitative approach using two-photon microscopy (TPM) imaging in combination with intravital staining of Evans blue dye (EBD), a far-red fluorescence dye, which potentially labels elastin. With focus on myofascia of the tibial anterior (TA) muscle, the fibril structure intravitally stained with EBD was observed at the depth level of collagen fibrous membrane above the muscle belly. The EBD-labelled fibril structure and orientation in myofascia indicated biomechanical responses to muscle activity and ageing. The orientation histograms of EBD-labelled fibrils were significantly modified depending upon the intensity of muscle activity and ageing. Moreover, the density of EBD-labelled fibrils in myofascia decreased with habitual exercise but increased with muscle immobilization or ageing. In particular, the diameter of EBD-labelled fibrils in aged mice was significantly higher. The orientation histograms of EBD-labelled fibrils after habitual exercise, muscle immobilization and ageing showed significant differences compared to control. Indeed, the histograms in bilateral TA myofascia of exercise mice made simple waveforms without multiple sharp peaks, whilst muscular immobilization or ageing significantly shifted a histogram with sustaining multiple sharp peaks. Therefore, the dynamics of fibre network with EBD fluorescence in response to the biomechanical environment possibly indicate functional tissue adaptation in myofascia. Furthermore, on the basis of the knowledge that neutrophil recruitment occurs locally in working muscles, we suggested the unique reconstruction mechanism involving neutrophilic elastase in the myofascial fibril structure. In addition to the elastolytic susceptibility of EBD-labelled fibrils, distinct immunoreactivities and activities of neutrophil elastase in the myofascia were observed after electric pulse stimulation-induced muscle contraction for 15min. Our findings of EBD-labelled fibril dynamics in myofascia through quantitative approach using TPM imaging and intravital fluorescence labelling potentially brings new insights to examine muscle physiology and pathology.

Real-Time Multidepth Multiphoton Microscopy Using Pixel-to-Pixel Focus-Switching

Multiphoton microscopy is a well-established technique for biomedical applications, but real-time multidepth multimodal multiphoton microscopy using non-imaging detection has barely been discussed. We demonstrate a novel label-free imaging system capable of generating multimodal multiphoton signals at different focal planes simultaneously. Two spatially overlapped and temporally interlaced beams are obtained by applying cost-effective electro-optic modulator (EOM)-based fast-switching light paths. The switching beams have different divergence properties, enabling imaging at different depths into samples. The EOM is synchronized to the pixel clock from the microscope, achieving pixel-to-pixel focus-switching. The capability of the imaging system is demonstrated by performing real-time multidepth two-photon fluorescence (TPF) and second-harmonic generation (SHG) imaging of freshly excised mouse lung lobes. TPF and SHG images are acquired at two wavelength ranges. One is between 415 and 455 nm, and the other is between 495 and 635 nm. The microenvironment of pulmonary alveoli is depicted by the distributions of both elastin fibers visualized by TPF and collagen fibers illustrated by SHG. Macrophages residing inside apparent alveolar lumens are also identified by TPF, which shows that the imaging system is capable of localizing biological objects in three dimensions and has the potential of monitoring in vivo cellular dynamics in the axial direction.

Morphological signs of connective tissue dysplasia as predictors of frequent post-exercise musculoskeletal disorders

BackgroundConnective tissue dysplasia (CTD) is a risk factor for musculoskeletal disorders. Changes caused by disorganization of collagen and elastin fibers lead to the inability of withstanding heavy mechanical stress. In clinical practice, diagnosis of these disorders depends on physical and anthropomorphic evaluation.MethodsForty-eight patients with frequent post-exercise musculoskeletal disorders were evaluated for CTD. The control group included 36 healthy participants. Both groups were evaluated via therapeutic examination with assessment of anthropometric indicators and physical-physiological evaluation, surveying and gathering of anamnesis. Based on testing results, study participants were evaluated on CTD presence and risk factors.ResultsAll experimental group patients had connective tissue dysplasia of moderate and severe degree, with a total score of 49.44 ± 13.1. Certain morphological characteristics showed prevalence, allowing to determine pathognomonic predictors of high predisposition to frequent post-exercise musculoskeletal disorders. Back pain (100%), asthenic syndrome and kyphotic spinal deformation (75%), high gothic palate, hypermobility of joints and the auricles, excessive elasticity (63%), varicose veins of the lower extremities (56%) and hemorrhoids (56%), changes in the shape of the legs and temporomandibular joint (50%) showed to be significant clinical factors indicating possible connective tissue dysplasia.ConclusionsThe presence of these diagnostically significant morphological signs of CTD in humans is a pathognomonic predictor of a high predisposition to frequent injuries. Their early detection helps promote proper appointment of adequate physical activity regimen and develop treatment for the underlying cause.

Electronic Blood Vessel

Summary Advances in bioelectronics have great potential to address unsolved biomedical problems in the cardiovascular system. By using poly(L-lactide-co-ϵ-caprolactone), which encapsulates liquid metal to make flexible and biodegradable electrical circuitry, we develop an electronic blood vessel that can integrate flexible electronics with three layers of blood-vessel cells, to mimic and go beyond the natural blood vessel. It can improve the endothelialization process through electrical stimulation and can enable controlled gene delivery into specific parts of the blood vessel via electroporation. The electronic blood vessel has excellent biocompatibility in the vascular system and shows great patency 3 months post-implantation in a rabbit model. The electronic blood vessel would be an ideal platform to enable diagnostics and treatments in the cardiovascular system and can greatly empower personalized medicine by creating a direct link of the vascular tissue-machine interface.

Vascular beneficial effects of silicon supplementation with enriched spirulina in hypertensive rat

Silicon (Si) is an essential trace element highly present in arteries. It is involved in the constitution and stabilization of elastin fibers. Its nutritional supply and bioavailability are often inadequate and, in human, Si content significantly declines with age. Vascular aging means increased arterial stiffness and remodelling of arterial wall with loss of elastic properties which might involve Si. Spirulina (Sp) micro algae have recognized nutritional properties and are able to incorporate minerals in a bioavailable form. Incorporating Si into spirulina is a way to obtain a bioavailable food supplement. We evaluated the effects of the nutritional supplement silicon-enriched spirulina (SpSi) on arterial system in an accelerated cardiovascular aging model, the hypertensive rat. Experiments were performed on hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats supplemented with SpSi or Sp during 3 months. Analysis consisted of measurements of arterial pressure and evaluation of ex vivo vascular function and structure on thoracic aorta. SpSi supplementation lowered arterial pressure in SHR and minimized morphometric alterations induced by hypertension. In SHR supplemented with SpSi, aortic wall thickness and elastic fibers fragmentation were substantially reduced. Collagen and elastin levels were increased in association with extracellular matrix degradation decrease. Vascular reactivity was improved with better contractile and vasorelaxant responses to various agonists. No effect was observed with Sp supplementation. The reduction of arterial pressure and the structural and functional changes observed in aortic wall of SHR rats after SpSi supplementation demonstrated the beneficial effects of this nutritional supplement and Si enrichment. This opens perspectives for the use of SpSi in prevention of vascular degenerative processes and potentially ageing, and in different conditions of Si deficiency.

Cell-free vascular grafts that grow with the host.

Cell-free small diameter vascular grafts, based on small intestinal submucosa (SIS) functionalized with heparin and vascular endothelial growth factor (VEGF) manufactured and implanted successfully into the arterial system of neonatal lambs, where they remained patent and grew in size with the host to a similar extent and with similar rate as native arteries. Acellular tissue engineered vessels (A-TEV) integrated seamlessly into the native vasculature and developed confluent, functional endothelium that afforded patency. The medial layer was infiltrated by smooth muscle cells, showed no signs of calcification and developed contractile function. The vascular wall underwent remarkable extracellular matrix remodeling exhibiting elastin fibers and even inner elastic lamina within six months. Taken together, our results suggest that VEGF-based A-TEVs may be suitable for treatment of congenital heart disorders to alleviate the need for repeated surgeries, which are currently standard practice.