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Keywords = vascular biomechanics

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15 pages, 2583 KiB  
Review
Multiparametric Ultrasound in the Differential Diagnosis of Soft Tissue Tumors: A Comprehensive Review
by Fabrizio Termite, Linda Galasso, Giacomo Capece, Federica Messina, Giorgio Esposto, Maria Elena Ainora, Irene Mignini, Raffaele Borriello, Raffaele Vitiello, Giulio Maccauro, Antonio Gasbarrini and Maria Assunta Zocco
Biomedicines 2025, 13(7), 1786; https://doi.org/10.3390/biomedicines13071786 - 21 Jul 2025
Viewed by 369
Abstract
Soft tissue tumors (STTs) are a heterogeneous group of mesenchymal neoplasms requiring accurate differentiation for optimal patient management. While histopathology remains the gold standard, imaging plays a crucial role in non-invasive assessment. Multiparametric ultrasound (mpUS) has emerged as a promising, cost-effective alternative to [...] Read more.
Soft tissue tumors (STTs) are a heterogeneous group of mesenchymal neoplasms requiring accurate differentiation for optimal patient management. While histopathology remains the gold standard, imaging plays a crucial role in non-invasive assessment. Multiparametric ultrasound (mpUS) has emerged as a promising, cost-effective alternative to MRI, integrating B-mode, color and power Doppler, shear wave elastography (SWE), and contrast-enhanced ultrasound (CEUS) to provide comprehensive morphological, vascular, and biomechanical insights. Each modality offers distinct yet complementary diagnostic value, enhancing accuracy and potentially reducing unnecessary biopsies. This narrative review aims to serve as a practical guide, providing a readily accessible reference for mpUS parameters useful in the differential diagnosis of soft tissue tumors. Full article
(This article belongs to the Special Issue Applications of Imaging Technology in Human Diseases)
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13 pages, 1846 KiB  
Article
Placental Shear Wave Elastography Assessment in Early and Late Fetal Growth Restriction
by Erika Cavanagh, Kylie Crawford, Jesrine Hong, Davide Fontanarosa, Christopher Edwards, Marie-Luise Wille, Jennifer Hong, Vicki L. Clifton and Sailesh Kumar
J. Clin. Med. 2025, 14(14), 4980; https://doi.org/10.3390/jcm14144980 - 14 Jul 2025
Viewed by 291
Abstract
Background/Objectives: The application of shear wave elastography (SWE) for the assessment of placental disease is still unproven and there is limited data correlating placental biomechanical properties with aberrations in fetal growth. This study investigated changes in placental shear wave velocity (SWV) in [...] Read more.
Background/Objectives: The application of shear wave elastography (SWE) for the assessment of placental disease is still unproven and there is limited data correlating placental biomechanical properties with aberrations in fetal growth. This study investigated changes in placental shear wave velocity (SWV) in early and late fetal growth restriction (FGR). Methods: We analyzed three study cohorts: Pregnancies with appropriate growth for gestational age (AGA) and those with early (<32 weeks’) and late (>32 weeks’) FGR. Mean SWV at two time points was compared in the following cohorts: all FGR vs. AGA, early FGR vs. late FGR, early FGR vs. AGA, and late FGR vs. AGA. Results: The study comprised 222 women—79 (35.6%) FGR and 143 (64.4%) AGA. Of the FGR pregnancies, 37 (46.8%) were early and 42 (53.2%) were late. On multivariate analysis mean, SWV was not increased in FGR compared to AGA placentae (β 0.21, 95% CI −0.17–0.60, p 0.28). It was also not increased in early FGR compared to late FGR or AGA placentae (β 0.36, 95% CI −0.06–0.77, p 0.09). We observed an effect measure modification by pre-eclampsia, increasing mean SWV to a greater extent in AGA compared to FGR cases. Conclusions: Although previous studies have shown an association between placental SWV and FGR, our study showed no difference between cases and controls. The interaction of pre-eclampsia indicated that SWE may have a greater role in pre-eclampsia than in FGR alone. Further investigation of the influence of increased maternal vascular pressure on placental stiffness would be beneficial. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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16 pages, 815 KiB  
Review
Microvascularization of the Vocal Folds: Molecular Architecture, Functional Insights, and Personalized Research Perspectives
by Roxana-Andreea Popa, Cosmin-Gabriel Popa, Delia Hînganu and Marius Valeriu Hînganu
J. Pers. Med. 2025, 15(7), 293; https://doi.org/10.3390/jpm15070293 - 7 Jul 2025
Viewed by 431
Abstract
Introduction: The vascular architecture of the vocal folds plays a critical role in sustaining the dynamic demands of phonation. Disruptions in this microvascular system are linked to various pathological conditions, including Reinke’s edema, hemorrhage, and laryngeal carcinoma. This review explores the structural [...] Read more.
Introduction: The vascular architecture of the vocal folds plays a critical role in sustaining the dynamic demands of phonation. Disruptions in this microvascular system are linked to various pathological conditions, including Reinke’s edema, hemorrhage, and laryngeal carcinoma. This review explores the structural and functional components of vocal fold microvascularization, with emphasis on pericytes, endothelial interactions, and neurovascular regulation. Materials and Methods: A systematic review of the literature was conducted using databases such as PubMed, Scopus, Web of Science, and Embase. Keywords included “pericytes”, “Reinke’s edema”, and “vocal fold microvascularization”. Selected studies were peer-reviewed and met criteria for methodological quality and relevance to laryngeal microvascular physiology and pathology. Results: The vocal fold vasculature is organized in a parallel, tree-like pattern with distinct arterioles, capillaries, and venules. Capillaries dominate the superficial lamina propria, while transitional vessels connect to deeper arterioles surrounded by smooth muscle. Pericytes, present from birth, form tight associations with endothelial cells and contribute to capillary stability, vessel remodeling, and mechanical protection during vibration. Their thick cytoplasmic processes suggest a unique adaptation to the biomechanical stress of phonation. Arteriovenous anastomoses regulate perfusion by shunting blood according to functional demand. Furthermore, neurovascular control is mediated by noradrenergic fibers and neuropeptides such as VIP and CGRP, modulating vascular tone and glandular secretion. The limited lymphatic presence in the vocal fold mucosa contributes to edema accumulation while also restricting carcinoma spread, offering both therapeutic challenges and advantages. Conclusions: A deeper understanding of vocal fold microvascularization enhances clinical approaches to voice disorders and laryngeal disease, offering new perspectives for targeted therapies and regenerative strategies. Full article
(This article belongs to the Special Issue Clinical Diagnosis and Treatment in Otorhinolaryngology)
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44 pages, 2343 KiB  
Review
Head and Neck 3D Bioprinting—A Review on Recent Advancements in Soft Tissue 3D Bioprinting and Medical Applications
by Iosif-Aliodor Timofticiuc, Ana Caruntu, Christiana Diana Maria Dragosloveanu, Andreea-Elena Scheau, Ioana Anca Badarau, Argyrios Periferakis, Serban Dragosloveanu, Andreea Cristiana Didilescu, Constantin Caruntu and Cristian Scheau
J. Funct. Biomater. 2025, 16(7), 240; https://doi.org/10.3390/jfb16070240 - 30 Jun 2025
Cited by 1 | Viewed by 1820
Abstract
Recent developments in 3D bioprinting offer innovative alternative solutions to classical treatments for head and neck defects. Soft tissues in an anatomical area as diverse in composition as the head and neck are complex in terms of structure and function. Understanding how cellular [...] Read more.
Recent developments in 3D bioprinting offer innovative alternative solutions to classical treatments for head and neck defects. Soft tissues in an anatomical area as diverse in composition as the head and neck are complex in terms of structure and function. Understanding how cellular interaction underlies functionality has led to the development of bioinks capable of mimicking the natural morphology and roles of different human parts. Moreover, from the multitude of recently developed materials, there are now many options for building scaffolds that potentiate the activity of these cells. The fidelity and accuracy of the utilized techniques ensure maximum precision in terms of model construction. Emerging technologies will allow for improved control of the scaffold, facilitating optimal results in the treatment of various pathologies, without concerns about the availability of donors, immunological response, or any other side effects that traditional treatments withhold. This paper explores the current landscape of bioprinted scaffolds and their applications in the head and neck region, with a focus on the properties and use of natural and synthetic bioinks in the attempt to replicate the biomechanical features of native tissues. Customization capabilities that support anatomical precision and biofunctionality are also addressed. Moreover, regulatory requirements, as well as current challenges related to biocompatibility, immune response, and vascularization, are critically discussed in order to provide a comprehensive overview of the pathway to clinical application. Full article
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25 pages, 3738 KiB  
Article
Morphometric, Biomechanical and Macromolecular Performances of β-TCP Macro/Micro-Porous Lattice Scaffolds Fabricated via Lithography-Based Ceramic Manufacturing for Jawbone Engineering
by Carlo Mangano, Nicole Riberti, Giulia Orilisi, Simona Tecco, Michele Furlani, Christian Giommi, Paolo Mengucci, Elisabetta Giorgini and Alessandra Giuliani
J. Funct. Biomater. 2025, 16(7), 237; https://doi.org/10.3390/jfb16070237 - 28 Jun 2025
Viewed by 1251
Abstract
Effective bone tissue regeneration remains pivotal in implant dentistry, particularly for edentulous patients with compromised alveolar bone due to atrophy and sinus pneumatization. Biomaterials are essential for promoting regenerative processes by supporting cellular recruitment, vascularization, and osteogenesis. This study presents the development and [...] Read more.
Effective bone tissue regeneration remains pivotal in implant dentistry, particularly for edentulous patients with compromised alveolar bone due to atrophy and sinus pneumatization. Biomaterials are essential for promoting regenerative processes by supporting cellular recruitment, vascularization, and osteogenesis. This study presents the development and characterization of a novel lithography-printed ceramic β-TCP scaffold, with a macro/micro-porous lattice, engineered to optimize osteoconduction and mechanical stability. Morphological, structural, and biomechanical assessments confirmed a reproducible microarchitecture with suitable porosity and load-bearing capacity. The scaffold was also employed for maxillary sinus augmentation, with postoperative evaluation using micro computed tomography, synchrotron imaging, histology, and Fourier Transform Infrared Imaging analysis, demonstrating active bone regeneration, scaffold resorption, and formation of mineralized tissue. Advanced imaging supported by deep learning tools revealed a well-organized osteocyte network and high-quality bone, underscoring the scaffold’s biocompatibility and osteoconductive efficacy. These findings support the application of these 3D-printed β-TCP scaffolds in regenerative dental medicine, facilitating tissue regeneration in complex jawbone deficiencies. Full article
(This article belongs to the Special Issue Functional Biomaterial for Bone Regeneration)
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12 pages, 1930 KiB  
Article
Histological Analysis of Intracranial Cerebral Arteries for Elastin Thickness, Wall Thickness, and Vessel Diameters: An Atlas for Computational Modeling and a Proposed Predictive Multivariable Model of Elastin Thickness
by Nishanth Thiyagarajah, Alex Witek, Mark Davison, Robert Butler, Ahmet Erdemir, John Tsiang, Mohammed Shazam Hussain, Richard Prayson, Mark Bain and Nina Z. Moore
J. Clin. Med. 2025, 14(12), 4320; https://doi.org/10.3390/jcm14124320 - 17 Jun 2025
Viewed by 428
Abstract
Background/Objectives: Fluid dynamic models of the cerebral vasculature are being developed to evaluate intracranial vascular pathology. Fluid–structure interaction modeling provides an opportunity for more accurate simulation of vascular pathology by modelling the vessel wall itself in conjunction with the fluid forces. Accuracy of [...] Read more.
Background/Objectives: Fluid dynamic models of the cerebral vasculature are being developed to evaluate intracranial vascular pathology. Fluid–structure interaction modeling provides an opportunity for more accurate simulation of vascular pathology by modelling the vessel wall itself in conjunction with the fluid forces. Accuracy of these models is heavily dependent on the parameters used. Of those studied, elastin has been considered a key component used in aortic and common carotid artery modeling. We studied elastin thickness to determine if there was significant variation between cerebral artery territories to suggest its importance in cerebral blood vessel biomechanical response and provide reference data for modeling intracranial elastin. Elastin thickness was compared to vessel location, thickness, diameter, and laterality within human intracranial arteries. Methods: Tissue was taken from five human cadaveric heads preserved in formaldehyde from each intracranial vessel distribution bilaterally and stained with Van Gieson stain for elastin. A total of 160 normal cerebral vascular artery specimens were obtained from 17 different cerebrovascular regions. Two reviewers measured elastin thickness for each sample at five different locations per sample using Aperio ImageScope (Leica Biosystems, Deer Park, IL, USA). Statistical analysis of the samples was performed using mixed-models repeated measures regression methods. Results: There was a significant difference between anterior circulation (6.01 µm) and posterior circulation (4.4 µm) vessel elastin thickness (p-value < 0.05). Additionally, two predictive models of elastin thickness were presented, utilizing a combination of anterior versus posterior circulation, vessel diameter, and vessel wall thickness, which demonstrated significance for prediction with anterior versus posterior combined with vessel diameter and wall thickness. Conclusions: Elastin thicknesses are significantly different between anterior and posterior circulation vessels, which may explain the differences seen in aneurysm rupture risk for anterior versus posterior circulation aneurysms. Additionally, we propose two potential models for predicting elastin thickness based on vessel location, vessel diameter, and vessel wall thickness, all of which can be obtained using preoperative imaging techniques. These findings suggest that elastin plays an important role in cerebral vascular wall integrity, and this data will further enable fluid–structure interaction modeling parameters to be more precise in an effort to provide predictive modeling for cerebrovascular pathology. Full article
(This article belongs to the Special Issue Personalized Diagnosis and Treatment for Intracranial Aneurysm)
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25 pages, 843 KiB  
Review
Considerations on the Development of Therapeutics in Vascular Calcification
by Ana M. Valentin Cabrera, Sophie K. Ashbrook and Joshua D. Hutcheson
J. Cardiovasc. Dev. Dis. 2025, 12(6), 206; https://doi.org/10.3390/jcdd12060206 - 29 May 2025
Viewed by 1073
Abstract
Cardiovascular disease is the leading cause of death worldwide. Vascular calcification, the deposition of calcium phosphate mineral in the arterial wall, is the most significant predictor of morbidity and mortality. Vascular calcification can present as either medial or intimal calcification. Medial calcification is [...] Read more.
Cardiovascular disease is the leading cause of death worldwide. Vascular calcification, the deposition of calcium phosphate mineral in the arterial wall, is the most significant predictor of morbidity and mortality. Vascular calcification can present as either medial or intimal calcification. Medial calcification is most prevalent among patients with chronic kidney disease. Intimal calcification is associated with atherosclerosis and chronic inflammation. In both cases, vascular smooth muscle cells undergo osteogenic differentiation, leading to mineral deposition and associated wall stiffening; however, the effects on cardiovascular function and morbidity vary depending on mineral morphology and location. This review investigates vascular calcification, the mechanisms leading to calcium deposition, and what to consider when developing therapeutics for vascular calcification. Full article
(This article belongs to the Section Basic and Translational Cardiovascular Research)
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32 pages, 6571 KiB  
Article
Exploring the Mechanical Properties of Bioprinted Multi-Layered Polyvinyl Alcohol Cryogel for Vascular Applications
by Argyro Panieraki, Nasim Mahmoodi, Carl Anthony, Rosemary J. Dyson and Lauren E. J. Thomas-Seale
J. Manuf. Mater. Process. 2025, 9(6), 173; https://doi.org/10.3390/jmmp9060173 - 26 May 2025
Cited by 1 | Viewed by 585
Abstract
Polyvinyl alcohol cryogels (PVA-C) are promising materials for vascular tissue engineering due to their biocompatibility, hydrophilicity, and tuneable mechanical properties. This study investigates the mechanical performance of multi-layered PVA-C constructs fabricated via sub-zero extrusion-based three-dimensional (3D) bioprinting. Samples with two, four, and six [...] Read more.
Polyvinyl alcohol cryogels (PVA-C) are promising materials for vascular tissue engineering due to their biocompatibility, hydrophilicity, and tuneable mechanical properties. This study investigates the mechanical performance of multi-layered PVA-C constructs fabricated via sub-zero extrusion-based three-dimensional (3D) bioprinting. Samples with two, four, and six alternating layers were evaluated to assess the effect of layered architecture on elastic and viscoelastic behaviour. Uniaxial tensile testing revealed that increasing the number of layers led to a moderate reduction in stiffness; for instance, at 20% strain, six-layered constructs showed a significantly lower (p < 0.05) Young’s modulus (36.7 ± 2.5 kPa) compared to two-layered ones (47.3 ± 3.1 kPa). Stress–strain curves exhibited nonlinear characteristics, better captured by quadratic (as opposed to linear) fitting, within the tested strain range (≤40%). Dynamic mechanical analysis demonstrated a frequency-independent storage modulus (E′) across 1–10 Hz, with subtle variations in viscoelastic response linked to the number of layers. Visual inspection confirmed improved print fidelity and hydration retention in thicker constructs. These findings demonstrate that a multi-layered design influences the mechanical profile of PVA-C and suggests potential for functionally graded design strategies to enhance compliance matching and mimic the biomechanics of native vessels in small-diameter vascular grafts. Full article
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20 pages, 7144 KiB  
Article
Biodynamic Characteristics and Blood Pressure Effects of Stanford Type B Aortic Dissection Based on an Accurate Constitutive Model
by Yiwen Wang, Libo Xin, Lijie Zhou, Xuefeng Wu, Jinong Zhang and Zhaoqi Wang
Appl. Sci. 2025, 15(11), 5853; https://doi.org/10.3390/app15115853 - 23 May 2025
Viewed by 374
Abstract
Aortic dissection (AD) is a highly lethal cardiovascular emergency, and clinical studies have found that a high percentage of AD patients are hypertensive. In previous studies, the AD model was simplified, such as by treating the vessel wall as a single-layer rigid material, [...] Read more.
Aortic dissection (AD) is a highly lethal cardiovascular emergency, and clinical studies have found that a high percentage of AD patients are hypertensive. In previous studies, the AD model was simplified, such as by treating the vessel wall as a single-layer rigid material, ignoring the complex biomechanical factors of the vascular lumen. This study elucidates key biomechanical mechanisms by which hypertension promotes primary AD progression using multiscale modeling. First, based on experimental data from longitudinal and circumferential uniaxial tensile testing of porcine aortic walls (5–7-month-old specimens), a constitutive model of the aortic wall was developed using the Holzapfel–Gasser–Ogden (HGO) framework. The material parameters were calibrated via inverse optimization in ABAQUS-ISIGHT, achieving close alignment with mechanical properties of the human aorta. Using this validated model to define the hyperelastic properties of the aortic wall, a multiphysics coupling platform was constructed in COMSOL Multiphysics 6.2, integrating computational fluid dynamics (CFD) and fluid–structure interaction (FSI) algorithms. This framework systematically quantified the effects of blood pressure (bp) fluctuations on compressive stresses, von Mises stresses, and deformation of the intimal flap within the AD lesion region. With constant blood rheology, elevated blood pressure enhances wall stresses (compressive and von Mises), and intima-media sheet deformation, this can trigger initial rupture tears, false lumen dilation, and branch arterial flow obstruction, ultimately deteriorating end-organ perfusion. Full article
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12 pages, 570 KiB  
Article
Topological Transformations in Hand Posture: A Biomechanical Strategy for Mitigating Raynaud’s Phenomenon Symptoms
by Arturo Tozzi
Int. J. Topol. 2025, 2(2), 6; https://doi.org/10.3390/ijt2020006 - 7 May 2025
Viewed by 1212
Abstract
Raynaud’s Phenomenon (RP), characterized by episodic reductions in peripheral blood flow, leads to significant discomfort and functional impairment. Existing therapeutic strategies focus on pharmacological treatments, external heat supplementation and exercise-based rehabilitation, but fail to address biomechanical contributions to vascular dysfunction. We introduce a [...] Read more.
Raynaud’s Phenomenon (RP), characterized by episodic reductions in peripheral blood flow, leads to significant discomfort and functional impairment. Existing therapeutic strategies focus on pharmacological treatments, external heat supplementation and exercise-based rehabilitation, but fail to address biomechanical contributions to vascular dysfunction. We introduce a computational approach rooted in topological transformations of hand prehension, hypothesizing that specific hand postures can generate transient geometric structures that enhance thermal and hemodynamic properties. We examine whether a flexed hand posture—where fingers are brought together to form a closed-loop toroidal shape—may modify heat transfer patterns and blood microcirculation. Using a combination of heat diffusion equations, fluid dynamics models and topological transformations, we implement a heat transfer and blood flow simulation to examine the differential thermodynamic behavior of the open and closed hand postures. We show that the closed-hand posture may preserve significantly more heat than the open-hand posture, reducing temperature loss by an average of 1.1 ± 0.3 °C compared to 3.2 ± 0.5 °C in the open-hand condition (p < 0.01). Microvascular circulation is also enhanced, with a 53% increase in blood flow in the closed-hand configuration (p < 0.01). Therefore, our findings support the hypothesis that maintaining a closed-hand posture may help mitigate RP symptoms by preserving warmth, reducing cold-induced vasoconstriction and optimizing peripheral flow. Overall, our topologically framed approach provides quantitative evidence that postural modifications may influence peripheral vascular function through biomechanical and thermodynamic mechanisms, elucidating how shape-induced transformations may affect physiological and pathological dynamics. Full article
(This article belongs to the Special Issue Feature Papers in Topology and Its Applications)
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14 pages, 7525 KiB  
Article
Novel Molecular Weight Gradient Hyaluronate Dissolving Microneedles for Sustained Intralesional Delivery and Photodynamic Activation of Hematoporphyrin in Port-Wine Stain Therapy
by Xueli Peng, Chenxin Yan, Nengquan Fan, Chaoguo Sun, Suohui Zhang and Yunhua Gao
Polymers 2025, 17(9), 1238; https://doi.org/10.3390/polym17091238 - 1 May 2025
Viewed by 545
Abstract
Port-wine stain (PWS), a progressive congenital vascular malformation characterized by ectatic dermal capillaries, demonstrates age-dependent lesion expansion and chromatic intensification, resulting in significant psychosocial comorbidity. While systemic hematoporphyrin (HP) administration remains the clinical paradigm for photodynamic therapy (PDT), its therapeutic utility is severely [...] Read more.
Port-wine stain (PWS), a progressive congenital vascular malformation characterized by ectatic dermal capillaries, demonstrates age-dependent lesion expansion and chromatic intensification, resulting in significant psychosocial comorbidity. While systemic hematoporphyrin (HP) administration remains the clinical paradigm for photodynamic therapy (PDT), its therapeutic utility is severely constrained by non-targeted biodistribution. Pharmacokinetic analyses reveal prolonged dermal retention and suboptimal lesion accumulation, predisposing 42% of patients to phototoxic reactions. To address these limitations, this work creatively suggested a local targeted drug delivery method based on soluble microneedles in response to the difficulties mentioned above. The rational design of a molecular weight (MW) HA gradient system enabled the engineering of ternary nanocomposite microneedles with enhanced biomechanical integrity (0.49 N/needle) and superior HP loading capacity, which collectively facilitated spatiotemporally controlled transdermal delivery of hematoporphyrin with complete dissolution within 30 min. The release performance, skin permeability, and storage stability of hematoporphyrin dissolving microneedles (HP-DMNs) have all been demonstrated in vitro. This study applies soluble microneedle technology to the delivery of HP in PWS for the first time. It avoids the risk of systemic exposure through precise local administration. It uses the rapid dissolution properties of microneedles to achieve high concentration and rapid release of drugs in skin lesions. This study provides a new strategy for sustained intralesional release and rapid drug delivery treatment of PWS and provides novel ideas for the development of new formulations of HP and related photosensitizers. Full article
(This article belongs to the Special Issue Polymers and Their Role in Drug Delivery, 2nd Edition)
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19 pages, 347 KiB  
Review
Sex-Specific Characteristics of Perivascular Fat in Aortic Aneurysms
by Katja Heller, Panagiotis Doukas, Christian Uhl and Alexander Gombert
J. Clin. Med. 2025, 14(9), 3071; https://doi.org/10.3390/jcm14093071 - 29 Apr 2025
Viewed by 591
Abstract
Aortic aneurysms (AAs), the dilation or widening of the aorta, lead to dissection or rupture with high morbidity and mortality if untreated. AA displays gender disparities in its prevalence, progression and outcomes, with women having worse outcomes and faster aneurysm growth. However, current [...] Read more.
Aortic aneurysms (AAs), the dilation or widening of the aorta, lead to dissection or rupture with high morbidity and mortality if untreated. AA displays gender disparities in its prevalence, progression and outcomes, with women having worse outcomes and faster aneurysm growth. However, current guidelines do not address gender dimorphism, emphasizing the urgent need for personalized treatment strategies and further research. Perivascular adipose tissue (PVAT), a unique type of fat surrounding blood vessels, plays a critical role in maintaining vasomotor tone and vascular homeostasis, with dysfunction associated with chronic inflammation and vessel-wall remodeling. Indeed, PVAT dysfunction promotes the development of aortic aneurysms, with hormonal and biomechanical factors exacerbating the pathological vascular microenvironment. The sexually dimorphic characteristics of PVAT include morphological, immunological, and hormonally mediated differences. Thus, targeting PVAT-mediated mechanisms may be a promising option for the (gender-specific) therapeutic management of cardiovascular pathologies. This review examines the emerging importance of PVAT in vascular health, its potential therapeutic implications for AA, and identifies gaps in the current state of research. Full article
(This article belongs to the Section Vascular Medicine)
20 pages, 3614 KiB  
Article
Transnasal PLGA Nanoparticles with Terpene Permeation Enhancers: Membrane Remodeling and Tight Junction Modulation for Enhanced Brain Drug Delivery
by Yi Zhang, Zishuo Guo, Haitong Zhang, Hongmei Wei, Tieshan Wang, Shouying Du and Pengyue Li
Int. J. Mol. Sci. 2025, 26(8), 3861; https://doi.org/10.3390/ijms26083861 - 18 Apr 2025
Cited by 1 | Viewed by 580
Abstract
Nasal nanodrug delivery has gained prominence as a non-invasive method for administering therapeutic agents to the brain. However, the limited nasal cavity volume and the low drug loading capacity of nanoparticles contribute to a reduced accumulation of the drug within the brain tissue. [...] Read more.
Nasal nanodrug delivery has gained prominence as a non-invasive method for administering therapeutic agents to the brain. However, the limited nasal cavity volume and the low drug loading capacity of nanoparticles contribute to a reduced accumulation of the drug within the brain tissue. Therefore, the aim of the present study was to investigate the role of the drug delivery combination “transnasal route + nanoparticle drug delivery system + chemical osmosis technology” in promoting drug accumulation in the brain. We constructed an in vitro olfactory sheath cell model based on the direct nose–brain pathway and a vascular endothelial cell model based on the indirect pathway, and investigated the transport behaviors and mechanisms of Poly(lactic-co-glycolicacid)-Nanoparticles (PLGA-NPs) in combination with two terpene aroma constituents (menthol and curcumol). Menthol and curcumol significantly improved the intracellular accumulation of PLGA-NPs, which may be related to changes in the endocytosis pathway and intercellular tight junction proteins. Meanwhile, the results of laser scanning confocal microscopy and atomic force microscopy showed that menthol and curcumol disrupted different tight junction proteins of vascular endothelial cells, and the biomechanical properties (e.g., rigidity and roughness) of the olfactory sheath cells and vascular endothelial cell cytomembranes were also greatly changed. The delivery system of “transnasal route + nanoparticle drug delivery system + chemical osmosis technology” has great potential for intranasal delivery of drugs for the treatment of brain diseases. Full article
(This article belongs to the Section Molecular Pharmacology)
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34 pages, 1745 KiB  
Systematic Review
Milestones in Mandibular Bone Tissue Engineering: A Systematic Review of Large Animal Models and Critical-Sized Defects
by Yannick M. Sillmann, Pascal Eber, Elizabeth Orbeta, Frank Wilde, Andrew J. Gross and Fernando P. S. Guastaldi
J. Clin. Med. 2025, 14(8), 2717; https://doi.org/10.3390/jcm14082717 - 15 Apr 2025
Cited by 1 | Viewed by 1086
Abstract
Background/Objectives: Mandibular reconstruction following trauma or oncologic resection is crucial for restoring function and aesthetics. While autologous bone grafting remains the gold standard, it presents challenges such as donor site morbidity and graft availability. Bone tissue engineering (BTE) offers an innovative alternative, integrating [...] Read more.
Background/Objectives: Mandibular reconstruction following trauma or oncologic resection is crucial for restoring function and aesthetics. While autologous bone grafting remains the gold standard, it presents challenges such as donor site morbidity and graft availability. Bone tissue engineering (BTE) offers an innovative alternative, integrating scaffolds, osteogenic cells, and bioactive factors to regenerate functional bone. This systematic review evaluates BTE strategies for mandibular reconstruction, focusing on critical-sized defects in large animal models and their translational potential for clinical applications. Methods: A systematic review was performed following PRISMA guidelines. Eligible studies involved large animal models and critical-sized mandibular defects treated with at least two BTE components (scaffold, osteogenic cells, or growth factors). Quality and bias assessments were conducted using ARRIVE guidelines and SYRCLE tools. Results: Of the 6088 studies screened, 27 met the inclusion criteria, focusing on critical-sized mandibular defects in large animal models such as pigs, sheep, and dogs. Common scaffolds included β-tricalcium phosphate (β-TCP), poly-lactic-co-glycolic acid (PLGA), and polycaprolactone (PCL), frequently combined with bone marrow-derived mesenchymal stem cells (BMSCs) and growth factors like recombinant human bone morphogenetic protein-2 (rhBMP-2). Preclinical outcomes demonstrated effective bone regeneration, vascularization, and biomechanical restoration. Advanced strategies, including in vivo bioreactors and 3D-printed scaffolds, further enhanced regeneration. However, challenges such as incomplete scaffold degradation, hypoxic conditions within constructs, and variability in growth factor efficacy and dose optimization were observed, emphasizing the need for further refinement to ensure consistent outcomes. Conclusions: BTE shows promise in mandibular reconstruction, achieving bone regeneration and functional restoration in preclinical models of critical-sized defects. However, challenges such as scaffold optimization, vascularization enhancement, and protocol standardization require further investigation to facilitate clinical translation. These findings emphasize the need for refinement to achieve consistent, scalable outcomes for clinical use. Full article
(This article belongs to the Section Dentistry, Oral Surgery and Oral Medicine)
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22 pages, 10058 KiB  
Review
Treatment Strategy for Subaxial Minimal Facet/Lateral Mass Fractures: A Comprehensive Clinical Review
by Chae-Gwan Kong and Jong-Beom Park
J. Clin. Med. 2025, 14(8), 2554; https://doi.org/10.3390/jcm14082554 - 8 Apr 2025
Viewed by 633
Abstract
Minimal facet and lateral mass fractures of the subaxial cervical spine (C3–C7) are a distinct subset of spinal injuries that present diagnostic and therapeutic challenges. These fractures often result from low-energy trauma or hyperextension mechanisms. They are frequently stable. However, subtle fracture instability [...] Read more.
Minimal facet and lateral mass fractures of the subaxial cervical spine (C3–C7) are a distinct subset of spinal injuries that present diagnostic and therapeutic challenges. These fractures often result from low-energy trauma or hyperextension mechanisms. They are frequently stable. However, subtle fracture instability and associated soft tissue injuries may lead to delayed instability, neurological compromise, and/or chronic severe pain if not properly identified. Accurate diagnosis relies on a combination of plain radiography, high-resolution computed tomography (CT), and magnetic resonance imaging (MRI) to assess bony and ligamentous integrity. Treatment strategy is determined based on fracture stability, neurological status, and radiographic findings. Most stable fractures can be effectively treated with conservative treatment, allowing for natural healing while minimizing complications. However, when instability is suspected—such as those with significant disc and ligamentous injuries, progressive deformity, or neurological deficits—surgical stabilization may be considered. The presence of vertebral artery injury (VAI) can further complicate management. To mitigate the risk of stroke, a multidisciplinary approach that includes neurosurgery, vascular surgery, and interventional radiology is needed. Surgical treatment aims to restore spinal alignment, maintain stability, and prevent further neurological deterioration with approaches tailored to individual fracture patterns and patient-specific factors. Advances in surgical techniques, perioperative management, and endovascular interventions for VAI continue refining treatment options to improve clinical outcomes while minimizing complications. Despite increasing knowledge of these fractures and associated vascular injuries, optimal treatment strategies remain unclear due to limited high-quality evidence. This review provides a comprehensive analysis of the anatomy, biomechanics, classification, imaging modalities, and treatment strategies for minimal facet and lateral mass fractures in the subaxial cervical spine, highlighting recent advancements in diagnostic tools, therapeutic approaches, and managing vertebral artery injuries. A more precise understanding of the natural history and optimal management of these injuries will help spine specialists refine clinical decision-making and improve patient outcomes. Full article
(This article belongs to the Section Orthopedics)
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