Elastin Fibers Research Articles

Mechanical and histological characteristics of aortic dissection tissues

Aims: This study investigated the association between the macroscopic mechanical response of aortic dissection (AoD) flap, its fibre features, and patient physiological features and clinical presentations.Methods: Uniaxial test was performed with tissue strips in both circumferential and longitudinal directions from 35 patients with (AoD:CC) and without (AoD:w/oCC) cerebral/coronary complications, and 19 patients with rheumatic or valve-related heart diseases (RH). A Bayesian inference framework was used to estimate the expectation of material constants (C1, D1, and D2) of the modified Mooney-Rivlin strain energy density function. Histological examination was used to visualise the elastin and collagen in the tissue strips and image processing was performed to quantify their area percentages, fibre misalignment and waviness.Results: The elastin area percentage was negatively associated with age (p = 0.008), while collagen increased about 6% from age 40 to 70 (p = 0.03). Elastin fibre was less dispersed and wavier in old patients and no significant association was found between patient age and collagen fibre dispersion or waviness. Features of fibrous microstructures, either elastin or collagen, were comparable between AoD:CC and AoD:w/oCC group. Elastin and collagen area percentages were positively correlated with C1 and D2, respectively, while the elastin and collagen waviness were negatively correlated with C1 and D2, respectively. Elastin dispersion was negatively correlated to D2. Multivariate analysis showed that D2 was an effective parameter which could differentiate patient groups with different age and clinical presentations, as well as the direction of tissue strip.Conclusion: Fibre dispersion and waviness in the aortic dissection flap changed with patient age and clinical presentations, and these can be captured by the material constants in the strain energy density function. Statement of significanceAortic dissection (AoD) is a severe cardiovascular disease. Understanding the mechanical property of intimal flap is essential for its risk evaluation. In this study, mechanical testing and histology examination were combined to quantify the relationship between mechanical presentations and microstructure features. A Bayesian inference framework was employed to estimate the expectation of the material constants in the modified Mooney-Rivlin constitutive equation. It was found that fibre dispersion and waviness in the AoD flap changed with patient age and clinical presentations, and these could be captured by the material constants. This study firstly demonstrated that the expectation of material constants can be used to characterise tissue microstructures and differentiate patients with different clinical presentations.

Alpinetin inhibits macrophage infiltration and atherosclerosis by improving the thiol redox state: Requirement of GSk3β/Fyn-dependent Nrf2 activation.

Alpinetin is a plant flavonoid isolated from Alpinia katsumadai Hayata with antioxidant and anti-inflammatory properties. Monocyte infiltration into the intima promotes atherosclerotic development and causes plaque instability at the later stage, which is profoundly influenced by various oxidants. In this study, we investigated whether alpinetin restores the redox state to inhibit monocyteinfiltration and ameliorates atherosclerosis. ApoE-deficient (ApoE-/- ) mice were fed a high-fat diet and treated with alpinetin. We found that alpinetin significantly attenuated atherosclerotic lesions and reduced necrotic core size associated with the reduction in infiltrated macrophages within the plaques. Alpinetin inhibited macrophage adhesion and migration, and the expression of chemokines and adhesion molecules, such as MCP-1, VCAM-1, and ICAM-1. Intraplaque MMP2 and MMP9 were reduced, while collagen contents were increased and elastin fiber was prevented from degradation in the alpinetin-treated mice. Data further showed that alpinetin reduced reactive oxygen species generation and promoted thiol-dependent glutathione and thioredoxin antioxidant systems in macrophages. Alpinetin activated Nfr2, an upstream activator of the thiol-dependent redox signaling by increasing the nuclear translocation. The nuclear accumulation of Nrf2 was enhanced by reducing nuclear export, which was achieved through the regulation of the GSk3β/Fyn pathway. Finally, inhibition of Nrf2 in HFD-apoE-/- mice blockaded the effect of alpinetin, which increased aortic macrophage recruitment and aggravatedatherosclerosis concurrently with elevating the expression of MCP-1, VCAM-1, and ICAM-1. Altogether, these findings indicated that alpinetin improved Nrf2-mediated redox homeostasis, which consequently inhibited macrophage infiltration and atherosclerosis, suggesting a useful compound for treating atherosclerosis.

Photooxidation and Pentagalloyl Glucose Cross-Linking Improves the Performance of Decellularized Small-Diameter Vascular Xenograft In Vivo.

Small-diameter vascular grafts have a significant need in peripheral vascular surgery and procedures of coronary artery bypass graft (CABG); however, autografts are not always available, synthetic grafts perform poorly, and allografts and xenografts dilate, calcify, and induce inflammation after implantation. We hypothesized that cross-linking of decellularized xenogeneic vascular grafts would improve the mechanical properties and biocompatibility and reduce inflammation, degradation, and calcification in vivo. To test this hypothesis, the bovine internal mammary artery (BIMA) was decellularized by detergents and ribozymes with sonication and perfusion. Photooxidation and pentagalloyl glucose (PGG) were used to cross-link the collagen and elastin fibers of decellularized xenografts. Modified grafts’ characteristics and biocompatibility were studied in vitro and in vivo; the grafts were implanted as transposition grafts in the subcutaneous of rats and the abdominal aorta of rabbits. The decellularized grafts were cross-linked by photooxidation and PGG, which improved the grafts’ biomechanical properties and biocompatibility, prevented elastic fibers from early degradation, and reduced inflammation and calcification in vivo. Short-term aortic implants in the rabbits showed collagen regeneration and differentiation of host smooth muscle cells. No occlusion and stenosis occurred due to remodeling and stabilization of the neointima. A good patency rate (100%) was maintained. Notably, implantation of non-treated grafts exhibited marked thrombosis, an inflammatory response, calcification, and elastin degeneration. Thus, photooxidation and PGG cross-linking are potential tools for improving grafts’ biological performance within decellularized small-diameter vascular xenografts.

Late onset cardiovascular dysfunction in adult mice resulting from galactic cosmic ray exposure

SummaryThe complex and inaccessible space radiation environment poses an unresolved risk to astronaut cardiovascular health during long-term space exploration missions. To model this risk, healthy male c57BL/6 mice aged six months (corresponding to an astronaut of 34 years) were exposed to simplified galactic cosmic ray (GCR5-ion; 5-ion sim) irradiation at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratories (BNL). Multi-modal cardiovascular functional assessments performed longitudinally and terminally revealed significant impairment in cardiac function in mice exposed to GCR5-ion compared to unirradiated controls, gamma irradiation, or single mono-energetic ions (56Fe or 16O). GCR5-ion-treated mice exhibited increased arterial elastance likely mediated by disruption of elastin fibers. This study suggests that a single exposure to GCR5-ion is associated with deterioration in cardiac structure and function that becomes apparent long after exposure, likely associated with increased morbidity and mortality. These findings represent important health considerations when preparing for successful space exploration.

Combined Treatment of Monopolar and Bipolar Radiofrequency Increases Skin Elasticity by Decreasing the Accumulation of Advanced Glycated End Products in Aged Animal Skin.

It is well known that skin aging is related to the destruction of collagen and elastin fibers by metalloproteinases (MMPs). Aged fibroblasts have a decreased ability to synthesize collagen and elastin. Nuclear factor erythroid 2-related factor 2 (NRF2) involves glyoxalase (GLO) activation, which inhibits the production of advanced glycated end products (AGE) and the expression of its receptor (RAGE). RAGE increases nuclear transcription factor-kappa B (NF-κB), which upregulates MMPs and decreases skin elasticity. NRF2 also decreases M1 macrophages, which secrete tumor necrosis factor-alpha (TNF-α), thereby decreasing AGE production. It is well known that radiofrequency (RF) decreases skin elasticity by increasing collagen synthesis. We evaluated whether RF increases skin elasticity via NRF2/GLO and whether they decrease AGE and RAGE expression in aged animal skin. We also compared the effects of RF based on the modes (monopolar or bipolar) or the combination used. In aged skin, NRF2, GLO-1, and M2 macrophage expression was decreased, and their expression increased when RF was applied. M1 and TNF-α demonstrated increased expression in the aged skin and decreased expression after RF application. AGE accumulation and RAGE, NF-κB, and MMP2/3/9 expression were increased in the aged skin, and they were decreased by RF. The papillary and reticular fibroblast markers showed decreased expression in young skin and increased expression in aged skin. The densities of collagen and elastin fiber in the aged skin were low, and they were increased by RF. In conclusion, RF leads to increased collagen and elastin fibers by increasing NRF2/GLO-1 and modulating M1/M2 polarization, which leads to decreased AGE and RAGE and, consequently, decreased NF-κB, which eventually slows collagen and elastin destruction. RF also leads to increased collagen and elastin fiber synthesis by increasing papillary and reticular fibroblast expression.

Two-Photon Excitation Fluorescence Microscopy of Rat Elastin Fiber In Vivo

Two-Photon Excitation Fluorescence Microscopy of Rat Elastin Fiber In Vivo

Impact of Notch3 Activation on Aortic Aneurysm Development in Marfan Syndrome.

Background The leading cause of mortality in patients with Marfan syndrome (MFS) is thoracic aortic aneurysm and dissection. Notch signaling is essential for vessel morphogenesis and function. However, the role of Notch signaling in aortic pathology and aortic smooth muscle cell (SMC) differentiation in Marfan syndrome (MFS) is not completely understood. Methods RNA-sequencing on ascending aortic tissue from a mouse model of MFS, Fbn1mgR/mgR, and wild-type controls was performed. Notch 3 expression and activation in aortic tissue were confirmed with real-time RT-PCR, immunohistochemistry, and Western blot. Fbn1mgR/mgR and wild-type mice were treated with a γ-secretase inhibitor, DAPT, to block Notch activation. Aortic aneurysms and rupture were evaluated with connective tissue staining, ultrasound, and life table analysis. Results The murine RNA-sequencing data were validated with mouse and human MFS aortic tissue, demonstrating elevated Notch3 activation in MFS. Data further revealed that upregulation and activation of Notch3 were concomitant with increased expression of SMC contractile markers. Inhibiting Notch3 activation with DAPT attenuated aortic enlargement and improved survival of Fbn1mgR/mgR mice. DAPT treatment reduced elastin fiber fragmentation in the aorta and reversed the differentiation of SMCs. Conclusions Our data demonstrated that matrix abnormalities in the aorta of MFS are associated with increased Notch3 activation. Enhanced Notch3 activation in MFS contributed to aortic aneurysm formation in MFS. This might be mediated by inducing a contractile phenotypic change of SMC. Our results suggest that inhibiting Notch3 activation may provide a strategy to prevent and treat aortic aneurysms in MFS.

A Mixture of Topical Forms of Polydeoxyribonucleotide, Vitamin C, and Niacinamide Attenuated Skin Pigmentation and Increased Skin Elasticity by Modulating Nuclear Factor Erythroid 2-like 2.

It is well-known that increased oxidative stress caused by ultraviolet B (UV-B) radiation induces melanogenesis and activates metalloproteinases (MMPs), which degrade collagen and elastin fibers, leading to decreased skin elasticity. Various antioxidant agents, such as vitamin C and niacinamide, have been evaluated for use as treatments for photoaging or skin pigmentation. In this study, we evaluated the ability of a topical liquid formula of polydeoxyribonucleotide (PDRN), vitamin C, and niacinamide (PVN) delivered via a microneedling therapy system (MTS) to attenuate photoaging and pigmentation by increasing nuclear factor erythroid 2-like 2 (NRF2)/heme oxygenase-1 (HO-1) and decreasing MMP expression in a UV-B-radiated animal model. The effects of the PVN were compared with those of individual PDRN and hydroquinone (HQ) compounds. The expression of NRF2/HO-1 significantly increased in response to HQ, PDRN, and PVN in UV-B-radiated animal skin. The activity of nicotinamide adenine dinucleotide phosphate hydrogen oxidase decreased in response to HQ, PDRN, and PVN, and the superoxide dismutase activity increased. The expression of tumor protein p53 and microphthalmia-associated transcription factor and tyrosinase activity decreased in response to HQ, PDRN, and PVN, and this decrease was accompanied by decreased melanin content in the skin. The expression of nuclear factor kappa-light-chain enhancer of activated B cells and MMP2/3/9 decreased in response to HQ, PDRN, and PVN in UV-B-radiated skin. However, the expression of collagen type I α1 chain and the amount of collagen fibers that were evaluated by Masson’s trichrome staining increased in response to HQ, PDRN, and PVN. The contents of elastin fibers, fibrillin 1/2 and fibulin 5 increased in response to HQ, PDRN, and PVN. In conclusion, PVN delivered via MTS led to decreased melanogenesis and destruction of collagen and elastin fibers by MMPs, and, thus, PVN decreased skin pigmentation and increased skin elasticity.

Annular atrophic lichen planus: a review of the literature.

Annular atrophic lichen planus (AALP) is a rare variant of lichen planus. It is differentiated from other variants of lichen planus by a reduction of elastin fibers in the superficial dermis, which is a feature specific to this subtype. It has clinical features of both annular and atrophic lichen planus and has a chronic course. AALP does not usually respond to topical or systemic steroids, and a consensus regarding a treatment ladder is yet to be reached. Topical tacrolimus may be considered as a treatment option. Annular atrophic lichen planus is a relatively unknown condition, which may remain undiagnosed and difficult to manage, owing to a paucity of literature and lack of consensus on management.

Improved Quantification of Cell Density in the Arterial Wall-A Novel Nucleus Splitting Approach Applied to 3D Two-Photon Laser-Scanning Microscopy.

Accurate information on vascular smooth muscle cell (VSMC) content, orientation, and distribution in blood vessels is indispensable to increase understanding of arterial remodeling and to improve modeling of vascular biomechanics. We have previously proposed an analysis method to automatically characterize VSMC orientation and transmural distribution in murine carotid arteries under well-controlled biomechanical conditions. However, coincident nuclei, erroneously detected as one large nucleus, were excluded from the analysis, hampering accurate VSMC content characterization and distorting transmural distributions. In the present study, therefore, we aim to (1) improve the previous method by adding a “nucleus splitting” procedure to split coinciding nuclei, (2) evaluate the accuracy of this novel method, and (3) test this method in a mouse model of VSMC apoptosis. After euthanasia, carotid arteries from SM22α-hDTR Apoe–/– and control Apoe–/– mice were bluntly dissected, excised, mounted in a biaxial biomechanical tester and brought to in vivo axial stretch and a pressure of 100 mmHg. Nuclei and elastin fibers were then stained using Syto-41 and Eosin-Y, respectively, and imaged using 3D two-photon laser scanning microscopy. Nuclei were segmented from images and coincident nuclei were split. The nucleus splitting procedure determines the likelihood that voxel pairs within coincident nuclei belong to the same nucleus and utilizes these likelihoods to identify individual nuclei using spectral clustering. Manual nucleus counts were used as a reference to assess the performance of our splitting procedure. Before and after splitting, automatic nucleus counts differed −26.6 ± 9.90% (p < 0.001) and −1.44 ± 7.05% (p = 0.467) from the manual reference, respectively. Whereas the slope of the relative difference between the manual and automated counts as a function of the manual count was significantly negative before splitting (p = 0.008), this slope became insignificant after splitting (p = 0.653). Smooth muscle apoptosis led to a 33.7% decrease in VSMC density (p = 0.008). Nucleus splitting improves the accuracy of automated cell content quantification in murine carotid arteries and overcomes the progressively worsening problem of coincident nuclei with increasing cell content in vessels. The presented image analysis framework provides a robust tool to quantify cell content, orientation, shape, and distribution in vessels to inform experimental and advanced computational studies on vascular structure and function.

Sildenafil (Viagra) Aggravates the Development of Experimental Abdominal Aortic Aneurysm.

BackgroundcGMP‐hydrolyzing phosphodiesterase type 5 (PDE5) regulates vascular smooth muscle cell (SMC) contraction by antagonizing cGMP‐dependent protein kinase I (PKGI)–dependent SMC relaxation. SMC contractile dysfunction is implicated in the pathogenesis of aortic aneurysm. PDE5 inhibitors have been used for treating erectile dysfunction, such as drug Viagra (sildenafil). However, a few clinical cases have reported the association of Viagra usage with aortic dissection, and reduced PDE5A expression was found in human aortic aneurysm tissues. Therefore, we aimed to investigate the effect of sildenafil on experimental abdominal aortic aneurysm (AAA), the most common form of aortic aneurysm in elderly men.Methods and ResultsAAA was induced in C57BL/6J male mice by periaortic elastase in combination with blocking elastin/collagen formation via 3‐aminopropionitrile fumarate salt for 35 days. PDE5A protein levels detected by immunostaining were significantly reduced in mouse AAA. Sildenafil application in drinking water significantly aggravated aortic wall dilation and elastin degradation with pre‐existing moderate AAA. The phosphorylation level of myosin light chain 2 at Ser19, a biochemical marker of SMC contraction, was significantly reduced by sildenafil in AAA. Proximity ligation assay further revealed that the interaction between cGMP and PKGI was significantly increased by sildenafil in AAA, suggesting an elevation of PKGI activation in AAA.ConclusionsSildenafil treatment aggravated the degradation of elastin fibers and progression of experimental AAA by dysregulating cGMP and contractile signaling in SMCs. Our findings may raise the caution of clinical usage of Viagra in aneurysmal patients.

Evidence of a functional clitoris in dolphins

In species that copulate during non-conceptive periods, such as humans and bonobos, sexual intercourse is known to be pleasurable for females. Dolphins also copulate throughout the year, largely to establish and maintain social bonds1. In dolphins, the clitoris is positioned in the anterior aspect of the vaginal entrance2, where physical contact and stimulation during copulation is likely. Clitoral stimulation seems to be important during female-female sexual interactions in common bottlenose dolphins (Tursiops truncatus), which rub each other's clitorises using snouts, flippers, or flukes3. Determining a sexual pleasure response in animals not amenable to neurobehavioral examination is difficult, but investigation of the clitoris may elucidate evidence of functionality. In this study, we assessed macro- and micromorphological features of the clitoris in common bottlenose dolphins to examine functional features, including erectile bodies with lacunae, extensible collagen and/or elastin fibers, and the presence and location of sensory nerves. Our observations suggest the clitoris of dolphins has well-developed erectile spaces, is highly sensitive to tactile stimulation, and is likely functional. VIDEO ABSTRACT.

Histomorphological studies on the testicular capsule of crossbred Large White Yorkshire boars (Sus scrofa domesticus)

The present study was conducted on the testes of six healthy adult Large White Yorkshire pigs. Parenchyma of testes of adult boars was surrounded by a thick fibrous testicular capsule composed of inner tunica vasculosa, middle tunica albuginea, and outer visceral layer of tunica vaginalis. Tunica vasculosa was prominent and characterised by loose connective tissue contained numerous blood vessels. Tunica albuginea was composed of irregular connective tissues madeup of collagen, elastin and reticular fibres. Visceral layer of tunica vaginalis was found as outer thin layer of testicular capsule comprised of mesothelium and connective tissue layer. Connective tissue layer was blended with underlying connective tissues of tunica albuginea.

Epigallocatechin gallate facilitates extracellular elastin fiber formation in induced pluripotent stem cell derived vascular smooth muscle cells for tissue engineering

Tissue engineered vascular grafts possess several advantages over synthetic or autologous grafts, including increased availability and reduced rates of infection and thrombosis. Engineered grafts constructed from human induced pluripotent stem cell derivatives further offer enhanced reproducibility in graft production. One notable obstacle to clinical application of these grafts is the lack of elastin in the vessel wall, which would serve to endow compliance in addition to mechanical strength. This study establishes the ability of the polyphenol compound epigallocatechin gallate, a principal component of green tea, to facilitate the extracellular formation of elastin fibers in vascular smooth muscle cells derived from human induced pluripotent stem cells. Further, this study describes the creation of a doxycycline-inducible elastin expression system to uncouple elastin production from vascular smooth muscle cell proliferative capacity to permit fiber formation in conditions conducive to robust tissue engineering.

Differential characterization of lumbar spine associated tissue histology with nonlinear optical microscopy.

Percutaneous endoscopic lumbar discectomy (PELD) is the major effective treatment for lumbar disc herniation, and rapid histological identification of dissected tissue is critical to guide the discectomy. In this work, we revealed the histological features of different types of peridural tissues of the lumbar spine by label-free multi-modal nonlinear optical microscopy. Stimulated Raman scattering (SRS) was used to extract lipid and protein distributions, while second harmonic generation (SHG) and two-photon excited fluorescence (TPEF) signals were applied to image the collagen and elastin fibers at the same time. Our results demonstrated that the nonlinear optical features of the dura and adjacent soft tissues were significantly different, showing the potentials of our method for intraoperative differentiation of these critical tissues and improving the surgical outcome of PELD.

The micro-structure and biomechanics of eyelid tarsus

Eyelid tarsus is a fibrocartilagenous extracellular matrix around meibomian glands providing structural support to eyelids and play important roles in the integrity of the ocular surface. There are no previous studies investigating the relationship between micro-structure and function of eyelid tarsus. To investigate the structure of extracellular matrix and the biomechanical properties of tarsus, rabbit tarsus were stained with hematoxylin and eosin (H&E), MASSON and Verhoeff's Van Gieson (EVG), distribution of collagen and elastin fibers in tarsus extracellular matrix were analyzed with scanning electron microscopy. Tarsus strips were collected and went through uniaxial tensile test with an Instron Universal Testing Machine. Data from 15 tarsus samples were included in the study. The initial tensile modulus was 2.554 ± 1.453 Mpa, and the final tensile modulus was 23.554 ± 3.657 Mpa, with an extensibility of 35.47 ± 7.46%. Collagen fibers formed peripheral layers of lamellae around meibomian glands, while the elastin fibres were organized in a parallel arrangement in horizontal and sagittal section, and in a crossed arrangement around meibomian glands. After tensile test, elastin fibres were stretched and arranged perpendicular to the direction of the collagen fibril lamellae. The findings of this study suggest that the extracellular matrix structure formed by collagen-elastin network contributes to a nonlinear mechanical characteristic of eyelid tarsus.

Transforming growth factor beta-1 and vascular endothelial growth factor in the recovery and formation of skin scars

Relevance. Scars are multi-tissue structures that significantly reduce the quality of life of the young, able-bodied population. The most socially significant variants are represented by hypertrophic and keloid postoperative scars and scars after burns, atrophic scars after acne vulgaris and striae. Growth factors, which are also used for their treatment, play a significant role in their formation and progression. The aim of this work is to summarize data on the participation of growth factors (transforming growth factor beta-1 and vascular endothelial growth factor) in the formation of a hypertrophic or atrophic scar. Materials and Methods. The study of literary sources of scientometric scientific bases was carried out. Results and Discussion . The study showed that the duration of the scarring phases preceding it is of great importance in scar formation, their prolongation leads to chronic inflammation and the attachment of an autoimmune component, an increase in the number of myofibroblasts due to inhibition of apoptosis and an increase in the synthesis of intercellular substance and immature forms of collagen, as well as thinning of the epidermis over scar. Growth factors such as growth factor beta-1 and vascular endothelial growth factor are capable of shifting the balance of these two main pathways or towards proliferative processes, contributing to an increase in the number of blood vessels in the hemomicrocirculatory bed, the number of mast cells and total cellularity, as well as, in some cases, the synthesis of keloid - that is, the formation of a hypertrophic or keloid scar. On the contrary, the prevalence of inflammatory processes leads to a decrease in cellularity, a decrease in blood vessels and intercellular substance, as well as damage to elastin and collagen fibers, forming the phenotype of an atrophic scar or striae. Conclusion. Growth factors play a key role in scar formation, contributing to an increase in the number of blood vessels in the hemomicrocirculatory bed, the number of mast cells and total cellularity, as well as, in some cases, the synthesis of keloid - that is, the formation of a hypertrophic or keloid scar.

Evaluation of Bi-Layer Silk Fibroin Grafts for Penile Tunica Albuginea Repair in a Rabbit Corporoplasty Model.

The use of autologous tissue grafts for tunica albuginea repair in Peyronie’s disease and congenital chordee is often restricted by limited tissue availability and donor site morbidity, therefore new biomaterial options are needed. In this study, bi-layer silk fibroin (BLSF) scaffolds were investigated to support functional tissue regeneration of tunica albuginea in a rabbit corporoplasty model. Eighteen adult male, New Zealand white rabbits were randomized to nonsurgical controls (NSC, N = 3), or subjected to corporoplasty with BLSF grafts (N = 5); decellularized small intestinal submucosa (SIS) matrices (N = 5); or autologous tunica vaginalis (TV) flaps (N = 5). End-point evaluations were cavernosography, cavernosometry, histological, immunohistochemical, and histomorphometric assessments. Maximum intracorporal pressures (ICP) following papaverine-induced erection were similar between all groups. Eighty percent of rabbits repaired with BLSF scaffolds or TV flaps achieved full rigid erections, compared to 40% of SIS reconstructed animals. Five-minute peak erections were maintained in 60% of BLSF rabbits, compared to 20% of SIS and TV flap reconstructed rabbits. Graft perforation occurred in 60% of TV group at maximum ICP compared to 20% of BLSF cohort. Neotissues supported by SIS and BLSF scaffolds were composed of collagen type I and elastin fibers similar to NSC. SIS and TV flaps showed significantly elevated levels of corporal fibrosis relative to NSC with a corresponding decrease in corporal smooth muscle cells expressing contractile proteins. BLSF biomaterials represent emerging platforms for corporoplasty and produce superior functional and histological outcomes in comparison to TV flaps and SIS matrices for tunica albuginea repair.

Structure-function relationships of TMJ lateral capsule-ligament complex

The human temporomandibular joint (TMJ) lateral capsule ligament (LCL) complex is debated as a fibrous capsule with distinct ligaments or ligamentous thickening, necessitating further evaluation of the complex and its role in TMJ anatomy and mechanics. This study explores the ultrastructural arrangement, biomechanical tensile properties, and biochemical composition of the human LCL complex including region-specific differences to explore the presence of a distinct temporomandibular ligament and sex-specific differences to inform evaluations of potential etiological mechanisms. LCL complex ultrastructural arrangement, biomechanical properties, and biochemical composition were determined using cadaveric samples. Statistical modeling assessed sex- and region-specific effects on LCL complex tissue properties. Collagen fiber coherency, collagen fiber bundle size, and elastin fiber count did not differ between sexes, but females trended higher in elastin fiber count. LCL complex water and sGAG content did not differ between sexes or regions, but collagen content was higher in the anterior region (311.0 ± 185.6 μg/mg) compared to the posterior region (221.0 ± 124.9 μg/mg) (p = 0.045) across sexes and in males (339.6 ± 170.6 μg/mg) compared to females (204.5 ± 130.7 μg/mg) (p = 0.006) across regions. Anterior failure stress (1.1 ± 0.7 MPa) was larger than posterior failure stress (0.6 ± 0.4 MPa) (p = 0.024). Regional differences confirm the presence of a mechanically and compositionally distinct temporomandibular ligament. Baseline sex-specific differences are critical for etiological investigations of sex disparities in TMJ disorders. These results have important biomechanical and clinical ramifications, providing critical baseline tissue material properties, informing the development of TMJ musculoskeletal models, and identifying new areas for etiologic investigations for temporomandibular disorders.

Cyclo-VEGI inhibits bronchial artery remodeling in a murine model of chronic asthma

Purpose/Aim: In the context of asthma, airway bronchial remodeling and angiogenesis in the bronchial mucosa are well established. Cyclopeptidic-vascular endothelial growth inhibitor (cyclo-VEGI) is an inhibitor of the vascular endothelial growth factor (VEGF) receptor that increases the proliferation of endothelial cells and the formation of new vessels. However, changes in the bronchial arteries of patients with asthma have not been clearly elucidated. We investigated whether structural changes occurred in bronchial arteries, as well as the effects of cyclo-VEGI in a mouse model of chronic asthma (in vivo) and human fibroblasts (in vitro). Materials and Methods: A validated mouse model of allergic airway inflammation with ovalbumin (OVA) as the causative allergen was used for the study. Mice were treated with cyclo-VEGI or fluticasone during OVA challenge. In vitro experiments were conducted to determine whether fibroblasts proliferated following elastin exposure and the effects of cyclo-VEGI on them. Results: OVA sensitization and challenge led to greater perivascular smooth muscle area, more elastic fibers, and elevated expression of vascular cell adhesion molecule (VCAM)-1 antigen. These phenomena indicated changes to bronchial arteries. Cyclo-VEGI and fluticasone treatment both inhibited airway hyper-responsiveness and inflammation. Cyclo-VEGI-treated mice exhibited decreased perivascular smooth muscle area, elastin fibers, and VCAM-1 expression. Fluticasone-treated mice exhibited reductions in perivascular smooth muscle but not in perivascular elastin or VCAM-1 expression. In vitro, fibroblast proliferation was enhanced by elastin treatment, which was inhibited by cyclo-VEGI treatment. Eotaxin expression was elevated in elastin-treated fibroblasts and decreased with cyclo-VEGI treatment. Conclusions: Vascular remodeling occurred in our mouse model of chronic asthma. Cyclo-VEGI could reduce airway inflammation and hyper-responsiveness by inhibiting VCAM-1 expression and elastin deposition around the bronchial arteries.