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Bioengineering and regenerative medicine strategies are promising for the treatment of vascular diseases. However, current limitations inhibit the ability of these approaches to be translated to clinical practice. Here we summarize some of the big bottlenecks that inhibit vascular regeneration in the disease applications of aortic aneurysms, stroke, and peripheral artery disease. We also describe the bottlenecks preventing three-dimensional bioprinting of vascular networks for tissue engineering applications. Finally, we describe emerging technologies and opportunities to overcome these challenges to advance vascular regeneration. Authors discuss big bottlenecks that inhibit vascular regeneration in the disease context of aortic aneurysm, stroke, and peripheral artery disease, along with emerging opportunities to overcome these challenges. [ABSTRACT FROM AUTHOR]

Marfan syndrome is a connective tissue disorder that affects multiple organs, with the most serious complications occurring in the cardiovascular system. Aortic root dilatation and dissection are particularly concerning. While the prevalence of Marfan syndrome is equal between genders, male patients have a higher risk of developing thoracic aortic aneurysm and dissection compared to females. A recent study using a mouse model of severe Marfan syndrome found that male mice had poorer survival rates and exhibited lower elastin content and more fragmented elastic fibers compared to female mice. The study suggests that material properties, aortic size, and wall integrity may be connected to dissection risk. Further research is needed to understand how age and sex contribute to dissection risk in Marfan syndrome. [Extracted from the article]

Pericytes are essential components of small blood vessels and are found in human aortic vasa vasorum. Prior work uncovered lower vasa vasorum density and decreased levels of pro‐angiogenic growth factors in adventitial specimens of human ascending thoracic aortic aneurysm. We hypothesized that adventitial extracellular matrix (ECM) from normal aorta promotes pericyte function by increasing pericyte contractile function through mechanisms deficient in ECM derived from aneurysmal aortic adventitia. ECM biomaterials were prepared as lyophilized particulates from decellularized adventitial specimens of human and porcine aorta. Immortalized human aortic adventitia‐derived pericytes were cultured within Type I collagen gels in the presence or absence of human or porcine adventitial ECMs. Cell contractility index was quantified by measuring the gel area immediately following gelation and after 48 h of culture. Normal human and porcine adventitial ECM increased contractility of pericytes when compared with pericytes cultured in absence of adventitial ECM. In contrast, aneurysm‐derived human adventitial ECM failed to promote pericyte contractility. Pharmacological inhibition of TGFβR1 and antibody blockade of α2β1 integrin independently decreased porcine adventitial ECM‐induced pericyte contractility. By increasing pericyte contractility, adventitial ECM may improve microvascular function and thus represents a candidate biomaterial for less invasive and preventative treatment of human ascending aortic disease. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES We hypothesized that expression and activity of nitric oxide synthase-3 enzyme (Nos3) in bicuspid aortic valve (BAV) aortopathy are related to tissue layer and Nos3 genotype. METHODS Gene expression of Nos3 and platelet and endothelial cell adhesion molecule-1 (Pecam1) and NOS activity were measured in intima-containing media and adventitial specimens of ascending aortic tissue. The presence of 2 Nos3 single-nucleotide polymorphisms (SNPs; −786T/C and 894G/T) was determined for non-aneurysmal (NA) and aneurysmal patients with BAV (n  = 40, 89, respectively); patients with tricuspid aortic valve (TAV) and aneurysm (n  = 151); and NA patients with TAV (n  = 100). RESULTS Elevated Nos3 relative to Pecam1 and reduced Pecam1 relative to a housekeeping gene were observed within intima-containing aortic specimens from BAV patients when compared with TAV patients. Lower Nos3 in the adventitia of aneurysmal specimens was noted when compared with specimens of NA aorta, independent of valve morphology. NOS activity was similar among cohorts in media/intima and decreased in the diseased adventitia, relative to control patients. Aneurysmal BAV patients exhibited an under-representation of the wild-type genotype for −786 SNP. No differences in genotype distribution were noted for 894 SNP. Primary intimal endothelial cells from patients with at least 1 C allele at −786 SNP exhibited lower Nos3 when compared with wild-type cells. CONCLUSIONS These findings of differential Nos3 in media/intima versus adventitia depending on valve morphology or aneurysm reveal new information regarding aneurysmal pathophysiology and support our ongoing assertion that there are distinct mechanisms giving rise to ascending aortopathy in BAV and TAV patients. [ABSTRACT FROM AUTHOR]

The article presents a study which explores the history of advances in understanding the vessels of vessels. It mentions about the approaches that strive to control angiogenesis and vasculogenesis potentiate mitigation of vasa vasorum–mediated contributions to cardiovascular diseases and emerging diseases involving the microcirculation.

Biodegradable synthetic elastomers with tunable mechanical and physicochemical properties remain attractive materials for soft tissue engineering. We have recently synthesized novel poly(1,3-diamino-2-hydroxypropane- co-glycerol sebacate)- co-poly(ethylene glycol) (APS- co-PEG) biodegradable elastomers. This class of PEGylated elastomers has widely tunable mechanical and degradation properties compared wtih currently available biodegradable elastomers. To further investigate the biological application of this class of elastomers, we fabricated hybrid APS- co-PEG/polycaprolactone (PCL) porous scaffolds by electrospinning. The fiber morphology, chemical composition, mechanical properties, degradability, and cytocompatibility of hybrid APS -co-PEG/PCL electrospun scaffolds were characterized. These scaffolds exhibited a wide range of mechanical properties and similar cytocompatibility to PCL scaffolds. Importantly, PEGylation inhibited platelet adhesion on all APS -co-PEG/PCL electrospun scaffolds when compared with PCL and APS/PCL scaffolds, suggesting a potential role in mitigating thrombogenicity in vivo. Additionally, APS- 25PEG/PCL scaffolds were found to be mechanically analogous to human heart valve leaflet and supported attachment of human aortic valve cells. These results reveal that hybrid APS- co-PEG/PCL scaffolds may serve as promising constructs for soft tissue engineering, especially heart valve tissue engineering. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Altered microRNA expression is implicated in cardiovascular diseases. Our objective was to determine microRNA signatures in thoracic aortic aneurysms (TAAs) and abdominal aortic aneurysms (AAAs) compared with control non-aneurysmal aortic specimens. We evaluated the expression of fifteen selected microRNA in human TAA and AAA operative specimens compared to controls. We observed significant upregulation of miR-221 and downregulation of miR-1 and -133 in TAA specimens. In contrast, upregulation of miR-146a and downregulation of miR-145 and -331-3p were found only for AAA specimens. Upregulation of miR-126 and -486-5p and downregulation of miR-30c-2*, -155, and -204 were observed in specimens of TAAs and AAAs. The data reveal microRNA expression signatures unique to aneurysm location and common to both thoracic and abdominal pathologies. Thus, changes in miR-1, -29a, -133a, and -221 are involved in TAAs and miR-145, -146, and -331-3p impact AAAs. This work validates prior studies on microRNA expression in aneurysmal diseases. [ABSTRACT FROM AUTHOR]

In vivo, growth factors exist both as soluble and as solid-phase molecules, immobilized to cell surfaces and within the extracellular matrix. We used this rationale to develop more biologically relevant approaches to study stem cell behaviors. We engineered stem cell microenvironments using ink-jet bioprinting technology to create spatially defined patterns of immobilized growth factors. Using this approach, we engineered cell fate toward the osteogenic lineage in register to printed patterns of bone morphogenetic protein (BMP) 2 contained within a population of primary muscle-derived stem cells (MDSCs) isolated from adult mice. This patterning approach was conducive to patterning the MDSCs into subpopulations of osteogenic or myogenic cells simultaneously on the same chip. When cells were cultured under myogenic conditions on BMP-2 patterns, cells on pattern differentiated toward the osteogenic lineage, whereas cells off pattern differentiated toward the myogenic lineage. Time-lapse microscopy was used to visualize the formation of multinucleated myotubes, and immunocytochemistry was used to demonstrate expression of myosin heavy chain (fast) in cells off BMP-2 pattern. This work provides proof-of-concept for engineering spatially controlled multilineage differentiation of stem cells using patterns of immobilized growth factors. This approach may be useful for understanding cell behaviors to immobilized biological patterns and could have potential applications for regenerative medicine. [ABSTRACT FROM AUTHOR]

The article presents information on a study which compared the osteogenic differentiation of F-Muscle-Derived Stem Cells (MDSCs) and M-MDSCs. It is stated that F-MDSCs and M-MDSCs had been stimulated with bone morphogenetic protein 4 (BMP4). It is also reported that M-MDSCs may contain more osteoprogenitor cells than F-MDSCs.

Introduction: Bicuspid aortic valve (BAV) associated aortopathy portends an increased risk of ascending aortic aneurysm formation and dissection/rupture. We previously showed increased oxidative stress-induced cell death for aortic smooth muscle cells (SMCs) isolated from BAV patients when compared to SMCs isolated from patients with the morphologically normal tricuspid aortic valve (TAV). Furthermore, there is evidence of increased activity of calpain, a calcium dependent protease that can regulate oxidative stress in vasculature, in BAV aortic tissue. Hypothesis: We hypothesize that oxidative stress-induced cell death in BAV-associated aortopathy is mediated by calpain-induced caspase-3. Methods: Calpain and caspase-3 activity were quantified in serum-deprived primary human SMC populations isolated from BAV (n=9) and TAV (n=12) aortic specimens treated with 1mM of tert-butyl hydroperoxide (tBHP) for 3 hours. We measured tBHP-induced cell death in the presence and absence of the calpain inhibitor calpeptin (30μM) in BAV (n=9) and TAV (n=8) using a MTS-based assay. Results: tBHP-induced calpain activity was higher for BAV SMCs when compared with TAV SMCs (65 ± 16.9% vs. 45.9 ± 5.9%, p=0.02). tBHP-induced caspase 3 activity was higher for BAV SMCs compared with TAV SMCs (222 ± 69% vs. 140 ± 8%, p<0.01, respectively). Calpain inhibition alleviated tBHP-induced cell death in TAV SMCs (66.4 ± 6.7% vs. 93.2 ± 9.3%, p=0.05), and did not affect BAV SMCs (53.6 ± 6.8% vs. 66.3 ± 5.9%, p=0.34). Conclusions: These data highlights the clear differences in cellular biology between TAV and BAV SMCs. It demonstrates that the increased vulnerability of BAV SMCs to oxidative stress compared to TAV SMCs may be due to caspase-3, which has been previously shown to be induced by calpain. Despite increased induction of calpain by tBHP in BAV SMCs, calpain inhibition did not affect oxidative stress induced cell death for BAV SMCs as it did for TAV SMCs. Therefore, calpain is unlikely to be an important effector in BAV SMCs as it is for TAV SMCs in regulating oxidative stress-induced cellular death. [ABSTRACT FROM AUTHOR]

To report outcomes of total arch replacement (TAR) with hypothermic circulatory arrest and bilateral antegrade cerebral perfusion (bACP) using an “arch first” approach for acute Type A aortic dissection (ATAAD). The “arch first” approach involved revascularization of the aortic arch branch vessels with uninterrupted ACP, before lower body circulatory arrest, while the patient was cooling.This was an observational study of aortic surgeries from 2010 to 2021. All patients who underwent TAR with bACP for ATAAD were included. Short-term and long-term outcomes were reported utilizing descriptive statistics and Kaplan-Meier survival estimation.A total of 215 patients were identified who underwent TAR + bACP for ATAAD. Age was 59.0 [49.0–67.0] years and 35.3% were female. 73 patients (34.0%) underwent a concomitant aortic root replacement, 188 (87.4%) had aortic cannulation, circulatory arrest time was 37.0 [26.0–52.0] minutes, and nadir temperature was 20.8 [19.4–22.5] degrees Celsius. 35 patients (16.3%) had operative mortality (STS definition), 17 (7.9%) had a new stroke, 79 (36.7%) had prolonged mechanical ventilation (>24 h), 35 (16.3%) had acute renal failure (by RIFLE criteria), and 128 (59.5%) had blood product transfusions. One-year survival was 77.1%, while 5-years survival was 67.1%. During follow-up, there were 23 (10.7%) reinterventions involving the descending thoracic aorta – either thoracic endovascular aortic repair or open thoracoabdominal aortic replacement.Among patients with ATAAD, short-term postoperative outcomes after TAR + bACP using the “arch first” approach are acceptable. Moreover, this operative strategy may furnish long-term durability, with a reasonably low reintervention rate and satisfactory overall survival. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to evaluate the therapeutic potential of human skeletal muscle-derived myoendothelial cells for myocardial infarct repair. Background: We have recently identified and purified a novel population of myoendothelial cells from human skeletal muscle. These cells coexpress myogenic and endothelial cell markers and produce robust muscle regeneration when injected into cardiotoxin-injured skeletal muscle. Methods: Myoendothelial cells were isolated from biopsies of human skeletal muscle using a fluorescence-activated cell sorter along with populations of regular myoblasts and endothelial cells. Acute myocardial infarction was induced in male immune-deficient mice, and cells were directly injected into the ischemic area. Cardiac function was assessed by echocardiography, and donor cell engraftment, angiogenesis, scar tissue, endogenous cardiomyocyte proliferation, and apoptosis were all evaluated by immunohistochemistry. Results: A greater improvement in left ventricular function was observed after intramyocardial injection of myoendothelial cells when compared with that seen in hearts injected with myoblast or endothelial cells. Transplanted myoendothelial cells generated robust engraftments within the infarcted myocardium, and also stimulated angiogenesis, attenuation of scar tissue, and proliferation and survival of endogenous cardiomyocytes more effectively than transplanted myoblasts or endothelial cells. Conclusions: Our findings suggest that myoendothelial cells represent a novel cell population from human skeletal muscle that may hold promise for cardiac repair. [Copyright &y& Elsevier]