ABSTRACT
Objective:To fundamentally solve the problems of valve dysfunction caused by limited size of artificial valve, high requirements for implantation technology, destruction of subvalvular structure and proliferation of fibrous endothelial tissue. We have developed a prosthetic valve with zero left ventricular occupancy. The valve frame is appropriately higher than the existing products, slightly chimney shaped, fully accommodates the movement of the valve leaves in the valve frame, and completely supraannular surgical implantation. This study uses this valve for preclinical animal test.Methods:Seven sheep underwent the replacement of the artificial valve under the direct vision of cardiopulmonary bypass. Warfarin was used for anticoagulation for 6 months 24 hours after operation. The blood biochemistry, anticoagulation and cardiac color Doppler ultrasound were detected after operation. The sheep were killed 180 days later for autopsy to observe whether the artificial valve caused thromboembolism. The efficacy and safety of valve were observed.Results:Two of the seven sheep died within 24 hours after operation, and five survived for a long time. Later, they were killed at 180 days. The mechanical properties of the artificial valve were good, and there was no thromboembolism around the artificial valve and important organs. The tissue layer of suture ring has been completely organized and endothelial cells, and the thickness of tissue layer is about 0.6-1.0 mm. The mitral valve of experimental animals can be opened and closed freely, with smooth surface and no abnormal echo. The follow-up of color Doppler ultrasound showed that the left ventricular ejection fraction was normal (0.60-0.70) before and 6 months after operation. The results of cross valve pressure difference and blood flow velocity of artificial valve were good (vmean was far lower than 5 mmHg(1 mmHg=0.133 kPa) and pmean was lower than 1 m/s) , suggesting that the hemodynamic performance of artificial valve was good. Left ventricular retrograde angiography showed that the artificial valve was completely located in the left atrium with good position and normal opening and closing. There was no obvious perivalvular leakage and other abnormalities. Within 7 days of blood test, the indexes of surgical stress were more abnormal than those before operation. At 12 and 24 weeks, there were no obvious abnormalities in blood routine test, liver and kidney function and other blood test indexes of animals in each group.Conclusion:The new chimney shaped mechanical valve implanted completely above the mitral annulus has good wear resistance, histocompatibility, antithrombotic and hemodynamic performance.
ABSTRACT
Objective Anti-calcification and surface modification of the transcatheter heart valve is the priority research area and development direction of bioprosthesis heart valve.In present study,the Arginine-Glycine-Aspartic acid(RGD) coating technology and anti-calcification with epoxy chloropropane(EC) treatment were applied to investigate surface modification property of the transcatheter heart valve compared to the traditional anti-calcification method with glutaraldehyde (GA) treatment to demonstrate the improvement of structure and surface biological properties of the transcatheter heart valve.Methods Morphological characteristics of mesenchymal stem cells(MSCs) seeded on the transcatheter heart valve with the various anticalcification treatments were observed by scanning electron microscopy and the apoptosis rates of MSCs seeded on the transcatheter heart valve with the various anti-calcification interventions were studied by TUNEL staining.The cell adhesion and expression of the cytoskeletal protein,Vinment of MSCs treated as described were analyzed by cell-counting method and fluorescence immunohistochemical method respectively.Results The apoptosis rate of MSCs was markedly decreased while the expression of vinment and the cell adhesion strength of MSCs were elevated in the groups of GA-EC and RGD-EC treatments.The biological indices of RGD-EC group has significant difference(P ＜ 0.05) compared with GA group.Conclusion Biological properties of the surface of transcatheter heart valve can be remarkably improved by GA-EC and RGD-EC anti-calcification treatments.
ABSTRACT
This research was carried out to investigate the effect of basic fibrous growth factor (bFGF) controlled release hydrogel nanoparticles on the proliferation and differentiation of mesenchymal stem cells. The dex-GMA-bFGF-NPs were prepared by an improved emulsion polymerization method; their morphology, size and encapsulated ratio were assessed by routine procedure. Dynamic dialysis method was used to determine the release characteristics of dex-GMA-bFGF-NPs in vitro. The secondary culture MSCs were divided into four groups according the different ingredients being added into the DMEM culture medium: free bFGF group (A), blank dex-GMA nanoparticles group (B), dex-GMA-bFGF nanoparticles group (C), nothing group (D). The proliferation of cultured MSCs was measured by using cell counting method, MTT method and flow cytometry. ALP kit was used to evaluate the ALP activity of the MSCs to show the differentiation of the cells by adding the dex-GMA-bFGF-NPs to the DMEM culture medium (C group) or bFGF only (A group). B group and D group were taken as the controls. The results were analyzed by statistical analysis software (SPSS11.0). All results showed that the shape of dex-GMA-bFGF-NPs was spherical. The encapsulated ratio was 88% and more than 85% of the encapsulated bFGF could be released during 14 days. The in vitro cellular study showed the control release of bFGF from nanoparticles could promote the proliferation of MSCs. After 12 days, the cell number in groups A, B and C was (21.97 +/- 0.25) x 10(4) cells/ml, (12.43 +/- 0.13) x 10(4) cells/ml, (27.45 +/- 0.78) x 10(4) cells/ml and (12.03 +/- 0.43) x 10(4) cells/ml, with the difference being statistically significant among them (P < 0.05). The flow cytometry revealed that the G2/M+S percentage in group C was the highest at 4-8 days after plate culture(P < 0.05). During the first 3 days, the proliferation and differentiation of BMSCs between group A and group B were of no significance (P > 0.05), but were much faster than those of group C and D. After 7 days, dex-GMA-bFGF-NPs could enhance BMSCs proliferation and differentiation continually, but bFGF had no enhancement any more, the difference between group A and group B became more significant (P < 0.05). So we made the conclusions the bFGF loading dex-GMA hydrogel nanoparticles can release bFGF more than 21 days and can promote the proliferation and differentiation of the BMSCs through a long period of controlled release of bFGF. Dex-GMA-bFGF-NPs may be an ideal controlled release carrier for bioactive growth factors.
Subject(s)
Animals , Female , Male , Rats , Bone Marrow Cells , Cell Biology , Cell Differentiation , Cell Proliferation , Cells, Cultured , Culture Media , Fibroblast Growth Factor 2 , Pharmacology , Mesenchymal Stem Cells , Cell Biology , Nanoparticles , Rats, Sprague-DawleyABSTRACT
0.05),while the levels of IL-8 and IL-6 declined,but were still significantly higher than that at immediately after induction of anesthesia(P