Search Results (14)

Retinitis pigmentosa (RP) is a progressive inherited retinal dystrophy (IRD) that primarily affects rod photoreceptor cells, leading to the degeneration of photoreceptors and the gradual loss of vision. While RP is one of the most studied IRDs, other neurodegenerative diseases affecting the retina and optic nerve, such as glaucoma, also involve common mechanisms of cellular stress and degeneration. Current therapeutic approaches under investigation include gene therapy, retina prosthesis, and neuroprotection. Among these approaches, gene therapy has shown promise, though challenges related to viral vector tropism and transduction efficiency persist. The adeno-associated virus (AAV) vector is commonly employed for gene delivery, but novel serotypes and engineered variants are being explored to improve specificity and efficacy. This study evaluates the gene transfer efficiency of the AAV6.2 vector following intravitreal injection into the murine retina. Male C57BL/6 mice (9 weeks old) were intravitreally injected with 1 µL of AAV2-CMV-EGFP, AAV6-CMV-EGFP, or AAV6.2-CMV-EGFP at a titer of 3.2 × 10¹² vg/mL per eye. Retinal transduction was assessed using in vivo fluorescence imaging, flat-mount imaging, and immunohistochemistry. EGFP expression in retinal ganglion cells, Müller cells, amacrine cells, and bipolar cells was quantitatively analyzed. All three AAV serotypes effectively transduced retinal ganglion cells, but AAV6.2 exhibited enhanced transduction in Müller cells and other neuronal retinal cells, including bipolar and amacrine cells. AAV6.2 demonstrated more localized expression around retinal blood vessels compared to the diffuse expression observed with AAV2. Immunohistochemical analysis revealed that AAV6.2 had significantly higher transduction efficiency in Müller cells (p < 0.001) compared to AAV2 and AAV6. AAV6.2 shows superior transduction efficiency in Müller cells, positioning it as a promising vector for gene therapies targeting retinal degenerative diseases such as RP. Its ability to effectively transduce Müller cells suggests potential applications in neuroprotection and gene replacement therapies. Full article

Background: Gastrointestinal angiodysplasia is a significant vascular anomaly characterized by dilated, tortuous blood vessels in the gastrointestinal tract. The current literature extensively documents the association between angiodysplasia and aortic stenosis, known as Heyde syndrome, characterized by the triad of aortic stenosis, GIB, and acquired von Willebrand syndrome. However, other valvular diseases, including mitral and tricuspid regurgitation, have also been implicated. This comprehensive systematic review aims to investigate the spectrum of valvular abnormalities, exploring the intricate mechanisms by which they contribute to gastrointestinal bleeding. Furthermore, it will evaluate the available surgical and nonsurgical treatment modalities, assessing their efficacy in mitigating the incidence of such bleeding. Methods: A comprehensive search of the Pubmed/MEDLINE database was conducted to identify relevant studies to retrieve relevant articles from August 2014 to August 2024. A combination of Medical Subject Heading (MeSH) terms and text words related to cardiac valvular diseases and GIB were used. MeSH terms included “gastrointestinal bleeding”, “heart valve diseases”, “hematochezia”, “heart valve prosthesis”, “bioprosthesis”, “native valve diseases”, and “mechanical valve”. Results: Forty-five papers met the inclusion criteria. Twenty-seven studies covered GIB in aortic valve disease, ten on mitral valve disease, two on tricuspid valve disease, and six on multiple valves. Conclusions: This systematic review demonstrates the association between angiodysplasia and aortic stenosis and highlights mitral regurgitation and tricuspid regurgitation as potential etiologies. Definitive management with valvuloplasty or valve replacement is vital to preventing the onset or recurrence of GIB in patients with valvular disease. Full article

Over 10% of patients undergoing aortic endograft implantation experience endoleaks within a few years. In the case of type 1a endoleaks, a crack forms between the aorta and the prosthesis collar, allowing blood to pass. This blood fills the aneurysmal sac and can lead to its rupture. None of the strategies, such as prostheses with barbs and hooks or ad hoc pharmacological therapies, can prevent the phenomenon. An alternative approach is to reduce diameter oscillations due to pulsating pressure to improve the endoprosthesis adhesion to the internal vessel walls during the initial post-implantation phases. To reach this objective, we propose to use a passive intra-aortic balloon pump (PIABP) inserted and then maintained inside the vessel immediately after the surgical procedure. We tested our hypothesis in a mechanical mock of the cardiovascular system. A silicon aorta with physiological behavior was created for this purpose. The PIABP was inflated to increasing pressures between systolic and diastolic values (120/80 mmHg). For each aorta and each condition, the variations in aortic diameter between systole and diastole, and the pressure variations, were measured. For the normal aorta, with a PIABP pressure of 110 mmHg, the variations in diameter were reduced by 38%. Assuming an endoprosthesis with a diameter of 30 mm (oversized by 5% compared to the diastolic diameter), the time the oscillations are higher than 30 mm is also reduced by 36%. The results are positive and suggest the usefulness of a biomechanical approach to the problem of type 1a endoleaks. Further in silico and clinical trials are necessary to validate the method. Full article

Background: Autologous vein grafts are widely used for bypass procedures in cardiovascular surgery. However, these grafts are susceptible to failure due to vein graft disease. Our study aimed to evaluate the impact of the latest-generation FRAME external support on vein graft remodeling in a preclinical model. Methods: We performed autologous internal jugular vein interposition grafting in porcine carotid arteries for one month. Four grafts were supported with a FRAME mesh, while seven unsupported grafts served as controls. The conduits were examined through flowmetry, angiography, macroscopy, and microscopy. Results: The one-month patency rate of FRAME-supported grafts was 100% (4/4), whereas that of unsupported controls was 43% (3/7, Log-rank p = 0.071). On explant angiography, FRAME grafts exhibited significantly more areas with no or mild stenosis (9/12) compared to control grafts (3/21, p = 0.0009). Blood flow at explantation was higher in the FRAME grafts (145 ± 51 mL/min) than in the controls (46 ± 85 mL/min, p = 0.066). Area and thickness of neo-intimal hyperplasia (NIH) at proximal anastomoses were similar for the FRAME and the control groups: 5.79 ± 1.38 versus 6.94 ± 1.10 mm², respectively (p = 0.558) and 480 ± 95 vs. 587 ± 52 μm²/μm, respectively (p = 0.401). However, in the midgraft portions, the NIH area and thickness were significantly lower in the FRAME group than in the control group: 3.73 ± 0.64 vs. 6.27 ± 0.64 mm², respectively (p = 0.022) and 258 ± 49 vs. 518 ± 36 μm²/μm, respectively (p = 0.0002). Conclusions: In our porcine model, the external mesh FRAME improved the patency of vein-to-carotid artery grafts and protected them from stenosis, particularly in the mid regions. The midgraft neo-intimal hyperplasia was two-fold thinner in the meshed grafts than in the controls. Full article

The objective of this study is to assess the ability of an Artificial Circulatory Phantom (ACP) to verify its accuracy in simulating the movement of artificial vessels vs. real vessels under changing cardiovascular parameters such as heartbeat, ejection fraction, and total peripheral resistance. The experiments were conducted with blood-like fluid that flows through two types of vessels: iliac arteries and different types of ePTFE vascular prostheses. Parameters such as diameter and tortuosity were measured and analyzed. The flow characteristics included a pulsating pattern with a frequency of 60–120 min⁻¹ and ejection volumes ranging from 70 to 115 mL. The results showed a predominantly positive correlation between wall displacement (W_d) and tortuosity index (T_i) for the iliac artery (R² = 0.981), as well as between Wd and mean tortuosity index (MT_i) (R² = 0.994). Similarly, positive correlations between Wd and T_i (R² = 0.942) and Wd and MT_i (R² = 0.922) were computed for the ePTFE vascular prosthesis. The ACP introduced in this study is a valuable tool for evaluating various vessel types and the spatial configurations of vascular prostheses under diverse hemodynamic conditions. These findings are promising for the advancement of novel approaches to the testing and design of vascular grafts, ultimately enhancing their patency rates in future applications. Full article

Small-dimeter blood vessels (<6 mm) are required in coronary bypass and peripheral bypass surgery to circumvent blocked arteries. However, they have poor patency rates due to thrombus formation, intimal hyperplasia at the distal anastomosis, and compliance mismatch between the native artery and the graft. This review covers the state-of-the-art technologies for improving graft patency with a focus on reducing compliance mismatch between the prosthesis and the native artery. The focus of this article is on biomimetic design strategies to match the compliance over a wide pressure range. Full article

Background: Autologous vein bypass provides excellent long-term results in critical limb-threatening ischemia (CLTI), but a substantial portion of patients have insufficient vein length. In limbs with two distal outflow vessels and limited vein length, a vascular prosthesis may be combined with autologous vein for a sequential composite bridge bypass (SCBB). Results regarding graft function, limb salvage and reinterventions are presented. Methods: Between January 2010 and December 2019, 47 consecutive SCBB operations with a heparin-bonded PTFE-prosthesis and autologous vein were performed. Grafts were followed with a duplex scan with prospective documentation in a computerized vascular database. Retrospective analysis of graft patency, limb salvage and patient survival was performed. Results: Mean follow-up was 34 months (range 1–127 months). 30-day mortality was 10.6% and 5-year patient survival 32%. Postoperative bypass occlusion occurred in 6.4% and late occlusions or graft stenoses in 30%. Two prostheses developed late infection and seven legs were amputated. Primary, primary assisted, secondary patency and limb salvage rate were 54%, 63%, 66% and 85% after 5 years, respectively. Conclusions: SCBB patency and limb salvage were good despite a high early postoperative mortality. Combination of a heparin-bonded PTFE-prosthesis and autologous vein appears to be a valuable tool in CLTI in case of insufficient vein. Full article

Focal vibration therapy seeks to restore the physiological function of tissues and the nervous system. Recommendations for vibration settings, e.g., that could improve residual limb health and prosthesis acceptance in people with amputation, are pending. To establish a physiological connection between focal vibration settings, clinical outcomes, and molecular and neuronal mechanisms, we combined the literature on focal vibration therapy, vibrotactile feedback, mechanosensitive Piezo ion channels, touch, proprioception, neuromodulation, and the recovery of blood vessels and nerves. In summary, intermittent focal vibration increases endothelial shear stress when applied superficially to blood vessels and tissues and triggers Piezo1 signaling, supporting the repair and formation of blood vessels and nerves. Conversely, stimulating Piezo1 in peripheral axon growth cones could reduce the growth of painful neuromas. Vibrotactile feedback also creates sensory inputs to the motor cortex, predominantly through Piezo2-related channels, and modulates sensory signals in the dorsal horn and ascending arousal system. Thus, sensory feedback supports physiological recovery from maladaptations and can alleviate phantom pain and promote body awareness and physical activity. We recommend focal vibration of phantom limb maps with frequencies from ~60–120 Hz and amplitudes up to 1 mm to positively affect motor control, locomotion, pain, nerves, and blood vessels while avoiding adverse effects. Full article

A significant drawback of the rigid synthetic vascular prostheses used in the clinic is the mechanical mismatch between the implant and the prosthetic vessel. When placing prostheses with radial elasticity, in which this deficiency is compensated, the integration of the graft occurs more favorably, so that signs of cell differentiation appear in the prosthesis capsule, which contributes to the restoration of vascular tone and the possibility of vasomotor reactions. Aortic prostheses fabricated by electrospinning from a blend of copolymers of vinylidene fluoride with hexafluoropropylene (VDF/HFP) had a biomechanical behavior comparable to the native aorta. In the present study, to ensure mechanical stability in the conditions of a living organism, the fabricated blood vessel prostheses (BVP) were cross-linked with γ-radiation. An optimal absorbed dose of 0.3 MGy was determined. The obtained samples were implanted into the infrarenal aorta of laboratory animals—Landrace pigs. Histological studies have shown that the connective capsule that forms around the prosthesis has signs of high tissue organization. This is evidenced by the cells of the fibroblast series located in layers oriented along and across the prosthesis, similar to the orientation of cells in a biological arterial vessel. Full article

Vascular replacement is one of the most effective tools to solve cardiovascular diseases, but due to the limitations of autologous transplantation, size mismatch, etc., the blood vessels for replacement are often in short supply. The emergence of artificial blood vessels with 3D bioprinting has been expected to solve this problem. Blood vessel prosthesis plays an important role in the field of cardiovascular medical materials. However, a small-diameter blood vessel prosthesis (diameter < 6 mm) is still unable to achieve wide clinical application. In this paper, a response surface analysis was firstly utilized to obtain the relationship between the contact angle and the gelatin/sodium alginate mixed hydrogel solution at different temperatures and mass percentages. Then, the self-developed 3D bioprinter was used to obtain the optimal printing spacing under different conditions through row spacing, printing, and verifying the relationship between the contact angle and the printing thickness. Finally, the relationship between the blood vessel wall thickness and the contact angle was obtained by biofabrication with 3D bioprinting, which can also confirm the controllability of the vascular membrane thickness molding. It lays a foundation for the following study of the small caliber blood vessel printing molding experiment. Full article

Background: Cardiovascular surgery is confronted by a lack of suitable materials for patch repair. Acellular animal tissues serve as an abundant source of promising biomaterials. The aim of our study was to explore the bio-integration of decellularized or recellularized pericardial matrices in vivo. Methods: Porcine (allograft) and ovine (heterograft, xenograft) pericardia were decellularized using 1% sodium dodecyl sulfate ((1) Allo-decel and (2) Xeno-decel). We used two cell types for pressure-stimulated recellularization in a bioreactor: autologous adipose tissue-derived stromal cells (ASCs) isolated from subcutaneous fat of pigs ((3) Allo-ASC and (4) Xeno-ASC) and allogeneic Wharton’s jelly mesenchymal stem cells (WJCs) ((5) Allo-WJC and (6) Xeno-WJC). These six experimental patches were implanted in porcine carotid arteries for one month. For comparison, we also implanted six types of control patches, namely, arterial or venous autografts, expanded polytetrafluoroethylene (ePTFE Propaten^® Gore^®), polyethylene terephthalate (PET Vascutek^®), chemically stabilized bovine pericardium (XenoSure^®), and detoxified porcine pericardium (BioIntegral^® NoReact^®). The grafts were evaluated through the use of flowmetry, angiography, and histological examination. Results: All grafts were well-integrated and patent with no signs of thrombosis, stenosis, or aneurysm. A histological analysis revealed that the arterial autograft resembled a native artery. All other control and experimental patches developed neo-adventitial inflammation (NAI) and neo-intimal hyperplasia (NIH), and the endothelial lining was present. NAI and NIH were most prominent on XenoSure^® and Xeno-decel and least prominent on NoReact^®. In xenografts, the degree of NIH developed in the following order: Xeno-decel > Xeno-ASC > Xeno-WJC. NAI and patch resorption increased in Allo-ASC and Xeno-ASC and decreased in Allo-WJC and Xeno-WJC. Conclusions: In our setting, pre-implant seeding with ASC or WJC had a modest impact on vascular patch remodeling. However, ASC increased the neo-adventitial inflammatory reaction and patch resorption, suggesting accelerated remodeling. WJC mitigated this response, as well as neo-intimal hyperplasia on xenografts, suggesting immunomodulatory properties. Full article

Peripheral artery occlusive disease is an emerging cardiovascular disease characterized by the blockage of blood vessels in the limbs and is associated with dysfunction, gangrene, amputation, and a high mortality risk. Possible treatments involve by-pass surgery using autologous vessel grafts, because of the lack of suitable synthetic small-diameter vascular prosthesis. One to five percent of patients experience vascular graft infection, with a high risk of haemorrhage, spreading of the infection, amputation and even death. In this work, an infection-proof vascular graft prototype was designed and manufactured by electrospinning 12.5% w/v poly-L-lactic-co-glycolic acid solution in 75% v/v dichloromethane, 23.8% v/v dimethylformamide and 1.2% v/v water, loaded with 0.2% w/w_PLGA. Polymer and tobramycin concentrations were selected after viscosity and surface tension and after HPLC-UV encapsulation efficiency (EE%) evaluation, respectively. The final drug-loaded prototype had an EE% of 95.58% ± 3.14%, with smooth fibres in the nanometer range and good porosity; graft wall thickness was 291 ± 20.82 μm and its internal diameter was 2.61 ± 0.05 mm. The graft’s antimicrobic activity evaluation through time-kill assays demonstrated a significant and strong antibacterial activity over 5 days against Staphylococcus aureus and Escherichia coli. An indirect cell viability assay on Normal Human Dermal Fibroblasts (NHDF) confirmed the cytocompatibility of the grafts. Full article

The replacement of affected blood vessels of the polymer material can cause imbalances in the blood haemostatic system. Changes in blood after the implantation of vascular grafts depend not only on the chemical composition but also on the degree of surface wettability. The Dallon^® H unsealed hydrophilic knitted vascular prosthesis double velour was assessed at work and compare with hydrophobic vascular prosthesis Dallon^®. Spectrophotometric studies were performed in the infrared and differential scanning calorimetry, which confirmed the effectiveness of the process of modifying vascular prostheses. Determination of the parameters of coagulation time of blood after contact in vitro with Dallon^® H vascular prosthesis was also carried out. Prolongation of activated thromboplastin time, decreased activity of factor XII, IX and VIII, were observed. The prolonged thrombin and fibrinogen were reduced in the initial period of the experiment. The activity of plasminogen and antithrombin III and protein C were at the level of control value. The observed changes in the values of determined parameters blood coagulation do not exceed the range of referential values for those indexes. The observed changes are the result of considerable blood absorptiveness by the prosthesis of blood vessels and their sealing. Full article

Bacterial cellulose (BC) is ultrafine, nanofibrillar material with an exclusive combination of properties such as high crystallinity (84%–89%) and polymerization degree, high surface area (high aspect ratio of fibers with diameter 20–100 nm), high flexibility and tensile strength (Young modulus of 15–18 GPa), high water-holding capacity (over 100 times of its own weight), etc. Due to high purity, i.e., absence of lignin and hemicellulose, BC is considered as a non-cytotoxic, non-genotoxic and highly biocompatible material, attracting interest in diverse areas with hallmarks in medicine. The presented review summarizes the microbial aspects of BC production (bacterial strains, carbon sources and media) and versatile in situ and ex situ methods applied in BC modification, especially towards bionic design for applications in regenerative medicine, from wound healing and artificial skin, blood vessels, coverings in nerve surgery, dura mater prosthesis, arterial stent coating, cartilage and bone repair implants, etc. The paper concludes with challenges and perspectives in light of further translation in highly valuable medical products. Full article