Abstract Background Tissue-engineered vascular grafts (TEVGs) offer potential to overcome limitations of current approaches for reconstruction in congenital heart disease by providing biodegradable ...scaffolds on which autologous cells proliferate and provide physiologic functionality. However, current TEVGs do not address the diverse anatomic requirements of individual patients. This study explores the feasibility of creating patient-specific TEVGs by combining 3-dimensional (3D) printing and electrospinning technology. Methods An electrospinning mandrel was 3D-printed after computer-aided design based on preoperative imaging of the ovine thoracic inferior vena cava (IVC). TEVG scaffolds were then electrospun around the 3D-printed mandrel. Six patient-specific TEVGs were implanted as cell-free IVC interposition conduits in a sheep model and explanted after 6 months for histologic, biochemical, and biomechanical evaluation. Results All sheep survived without complications, and all grafts were patent without aneurysm formation or ectopic calcification. Serial angiography revealed significant decreases in TEVG pressure gradients between 3 and 6 months as the grafts remodeled. At explant, the nanofiber scaffold was nearly completely resorbed and the TEVG showed similar mechanical properties to that of native IVC. Histological analysis demonstrated an organized smooth muscle cell layer, extracellular matrix deposition, and endothelialization. No significant difference in elastin and collagen content between the TEVG and native IVC was identified. There was a significant positive correlation between wall thickness and CD68+ macrophage infiltration into the TEVG. Conclusions Creation of patient-specific nanofiber TEVGs by combining electrospinning and 3D printing is a feasible technology as future clinical option. Further preclinical studies involving more complex anatomical shapes are warranted.
Current commercialized small-diameter arterial grafts have not shown clinical effectiveness due to their poor patency rates. The present study evaluated the feasibility of an arterial bioresorbable ...vascular graft, which has a porous sponge-type scaffold, as a small-diameter arterial conduit.
The grafts were constructed by a 50:50 poly (1-lactic-co-ε-caprolactone) copolymer (PLCL) scaffold reinforced by a poly (1-lactic acid) (PLA) nanofiber. The pore size of the PLCL scaffold was adjusted to a small size (12.8 ± 1.85 μm) or a large size (28.5 ± 5.25 μm). We compared the difference in cellular infiltration, followed by tissue remodeling, between the groups. The grafts were implanted in 8- to 10-week-old female mice (n = 15 in each group) as infrarenal aortic interposition conduits. Animals were monitored for 8 weeks and euthanized to evaluate neotissue formation.
No aneurysmal change or graft rupture was observed in either group. Histologic assessment demonstrated favorable cell infiltration into scaffolds, neointimal formation with endothelialization, smooth muscle cell proliferation, and elastin deposition in both groups. No significant difference was observed between the groups. Immunohistochemical characterization with anti-F4/80 antibody demonstrated that macrophage infiltration into the grafts occurred in both groups. Staining for M1 and M2, which are the two major macrophage phenotypes, showed no significant difference between groups.
Our novel bioresorbable vascular grafts showed well-organized neointimal formation in the high-pressure arterial circulation environment. The large-pore scaffold did not improve cellular infiltration and neotissue formation compared with the small-pore scaffold.
Abstract Objective Bioresorbable vascular grafts are biologically active grafts that are entirely reconstituted by host-derived cells through an inflammation-mediated degradation process. ...Calcification is a detrimental condition that can severely affect graft performance. Therefore, prevention of calcification is of great importance to the success of bioresorbable arterial vascular grafts. The objective of this study was to test whether fast-degrading (FD) bioresorbable arterial grafts with high cellular infiltration will inhibit calcification of grafts. Methods We created two versions of bioresorbable arterial vascular grafts, slow-degrading (SD) grafts and FD grafts. Both grafts had the same inner layer composed of a 50:50 poly( l -lactic-co-ε-caprolactone) copolymer scaffold. However, the outer layer of SD grafts was composed of poly( l -lactic acid) nanofiber, whereas the outer layer of FD grafts was composed of a combination of poly( l -lactic acid) and polyglycolic acid nanofiber. Both grafts were implanted in 8- to 10-week-old female mice (n = 15 in the SD group, n = 10 in the FD group) as infrarenal aortic interposition conduits. Animals were observed for 8 weeks. Results von Kossa staining showed calcification in 7 of 12 grafts in the SD group but zero in the FD group ( P < .01, χ2 test). The cell number in the outer layer of FD grafts was significantly higher than in the SD grafts (SD, 0.87 ± 0.65 × 103 /mm2 ; FD, 2.65 ± 1.91 × 103 /mm2 ; P = .02). Conclusions The FD bioresorbable arterial vascular graft with high cellular infiltration into the scaffold inhibited calcification of grafts.
Bioresorbable vascular grafts (BVGs) can transform biologically into active blood vessels and represent an alternative to traditional synthetic conduits, which are prone to complications such as ...infection and thrombosis. Although platelet-derived growth factors and c-Kit positive cells play an important role in smooth muscle cell (SMC) migration and proliferation in vascular injury, atherosclerosis, or allograft, their roles in the vascular remodeling process of an arterial BVG remains unknown. Thus, we assessed the neottisue formation on arterial BVG remodeling by administrating imatinib, which is both a platelet-derived growth factor receptor kinase inhibitor and c-Kit receptor kinase inhibitor, in a murine model.
BVGs were composed of an inner poly(L-lactic-co-ε-caprolactone) copolymer sponge layer and an outer electrospun poly(L-lactic acid) nanofiber layer, which were implanted into the infrarenal abdominal aortas of C57BL/6 mice. After graft implantation, saline or 100 mg/kg of imatinib was administrated intraperitoneally daily for 2 weeks (n = 20 per group). Five mice in each group were scheduled to be humanely killed at 3 weeks and 15 at 8 weeks, and BVGs were explanted for histologic assessments.
Graft patency during the 8-week observational period was not significantly different between groups (control, 86.7% vs imatinib, 80.0%; P > .999). Neotissue formation consisting of endothelialization, smooth muscle proliferation, and deposition of collagen and elastin was not observed in either group at 3 weeks. Similar endothelialization was achieved in both groups at 8 weeks, but thickness and percent area of neotissue formation were significantly higher in the control group than in the imatinib group, (thickness, 30.1 ± 7.2 μm vs 19.6 ± 4.5 μm P = .001; percent area, 9.8 ± 2.7% vs 6.8 ± 1.8% P = .005). Furthermore, SMC layer and deposition of collagen and elastin were better organized at 8 weeks in the control group compared with the imatinib group. The thickness of SMC layer and collagen fiber area were significantly greater at 8 weeks in the control group than in the imatinib group (P < .001 and P = .026, respectively). Because there was no difference in the inner diameter of explanted BVGs (831.7 ± 63.4 μm vs 841.8 ± 41.9 μm; P = .689), neotissue formation was thought to advance toward the outer portion of the BVG with degradation of the polymer scaffold.
Imatinib attenuates neotissue formation during vascular remodeling in arterial bioresorbable vascular grafts (BVGs) by inhibiting SMC layer formation and extracellular matrix deposition.
This study demonstrated that imatinib attenuated neotissue formation during vascular remodeling in arterial Bioresorbable vascular graft (BVG) by inhibiting smooth muscle cell formation and extracellular matrix deposition. In addition, as imatinib did not modify the inner diameter of BVG, neotissue advanced circumferentially toward the outer portion of the neovessel. Currently, BVGs have not yet been clinically applied to the arterial circulation. The results of this study are helpful for the design of BVG that can achieve an optimal balance between polymer degradation and neotissue formation.
We evaluated the probability of vertebrobasilar system malperfusion due to occlusion of the left subclavian artery as assessed by preoperative magnetic resonance angiography in patients scheduled to ...undergo thoracic aortic surgery.
(Study 1) From January 2000 through March 2009, we studied variations of vertebral arteries in 301 patients scheduled to undergo thoracic aortic surgery. We classified vertebral artery variations into 3 categories according to the findings on preoperative magnetic resonance angiography: connection type, interrupted right vertebral artery, and interrupted left vertebral artery. (Study 2) From February 2007 through January 2010, we evaluated the cerebral complication in 41 patients who had occlusion of the left subclavian artery with a stent graft.
(Study 1) On preoperative magnetic resonance angiography, the vertebral artery was classified as connection type in 247 patients, interrupted right vertebral artery in 34, and interrupted left vertebral artery in 20. (Study 2) We performed subclavian obstruction test, left-right subclavian artery bypass, or left subclavian artery-left common carotid artery bypass to the 3 patients with interrupted right vertebral artery, respectively. Forty patients (98%) out of 41 patients had no complication after occlusion of the left subclavian artery.
Preoperative magnetic resonance angiography is useful for detection of the patients with high risk of vertebrobasilar system malperfusion due to occlusion of the left subclavian artery.
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