To reassess the significance of AGEs in cataract formation in diabetic animals, we measured amounts of AGEs in lens crystallins from STZ-induced diabetic animals with a newly developed ELISA. Lenses were removed at 5 and 20 wk after STZ injection. In 20-wk diabetic rats, all lenses were cataractous but not in control rats. In 20-wk diabetic compared with control rats, significant increases were observed in AGEs (172.3 +/- 18.3 vs. 14.3 +/- 1.7 AU, P < 0.01) and fluorescence (2.04 +/- 0.22 vs. 1.27 +/- 0.10 AU, P < 0.05). The amounts of AGEs in lens crystallins, measured by the ELISA, were > 12-fold higher in diabetic rats. In agreement with earlier studies, we found that fluorescence in lens crystallins increased by 61% in diabetic rats. In 5-wk diabetic rats, all lenses were noncataractous. In 5-wk diabetic compared with control rats, significant increases were observed in AGEs (84.1 +/- 7.7 vs. 9.4 +/- 1.5 AU, P < 0.01) and fluorescence (1.45 +/- 0.06 vs. 1.05 +/- 0.06 AU, P < 0.01). Analysis of the AGE content by ELISA showed that accumulation of AGEs in diabetic lens crystallins does markedly occur with time, and a large amount of AGEs exists in the diabetic (cataractous) lens crystallins. The disproportionate elevation of AGEs, measured by the ELISA, compared with fluorescence suggests that the actual levels of AGEs in cataractous lens crystallins from diabetic animals are higher than previously anticipated, and nonfluorescent AGEs may exist in diabetic lens crystallins.(ABSTRACT TRUNCATED AT 250 WORDS)
Objective
Bioresorbable vascular grafts are biologically active grafts which are entirely reconstituted by host-derived cells through an inflammation-mediated degradation process. Calcification is a detrimental condition that can severely impact graft performance. Therefore, prevention of calcification is of great importance to the success of bioresorbable arterial vascular grafts. The objective of this study is to test whether fast degrading bioresorbable arterial grafts with high cellular infiltration will inhibit calcification of grafts.
Methods
We created two versions of bioresorbable arterial vascular grafts: 1) Slow Degrading (SD) grafts and 2) Fast Degrading (FD) grafts. Both grafts had the same inner layer composed of a 50:50 poly (l-lactic-co-ε-caprolactone) copolymer (PLCL) scaffold. However, the outer layer of SD grafts was composed of poly (l-lactic acid) (PLA) nano-fiber whereas the outer layer of FD grafts was composed of a combination of PLA and polyglycolic acid (PGA) nano-fiber. Both grafts were implanted in 8–10 week old female mice (n = 15 in the SD group, n = 10 in the FD group) as infra-renal aortic interposition conduits. Animals were followed for 8 weeks.
Results
Von Kossa staining showed calcification in 7 out of 12 grafts in the SD group, but zero in the FD group (P<.01, chi-square test). The cell number in the outer layer of FD grafts was significantly higher than SD grafts (SD: 0.87 ± 0.65 × 103/mm2 vs. FD: 2.65 ± 1.91 × 103/mm2, P=.02).
Conclusions
The fast degrading bioresorbable arterial vascular graft with high cellular infiltration into the scaffold inhibited calcification of grafts.
Background
Current commercialized small-diameter arterial grafts have not shown clinical effectiveness due to their poor patency rates. The purpose of the present study is to evaluate the feasibility of arterial bioresorbable vascular graft, which has a porous sponge type scaffold, as a small-diameter arterial conduit.
Methods
The grafts were constructed by a 50:50 poly (l-lactic-co-ε-caprolactone) copolymer (PLCL) scaffold reinforced by a poly (l-lactic acid) (PLA) nano-fiber. 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 8–10 week old female mice (n = 15 in each group) as infra-renal aortic interposition conduits. Animals were followed for 8 weeks and sacrificed to evaluate neotissue formation.
Results
No aneurysmal change or graft rupture was observed in both groups. 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.
Conclusions
Our novel bioresorbable vascular grafts showed well-organized neointimal formation in the high pressure arterial circulation environment. Whereas the large pore size scaffold did not improve cellular infiltration and neotissue formation when compared to the small pore scaffold.
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