Calcification-resistant Effect of Surface-modified Biologic Arteries by Sulfonated Polyethyleneoxide / 대한흉부외과학회지

BACKGROUND: Calcific degeneration is the major cause of clinical failure of glutaraldehyde (GA) crosslinked bioprosthetic tissues implanted in the body and necessitates the reoperation or causes death. Surface modification of biologic tissues using sulfonated polyethyleneoixde (PEO-SO3) has been suggested to significantly enhance blood compatibility, biostability and calcification-resistance by means of the synergistic effect of highly mobile and hydrophilic PEO chains and electrical repulsion of negatively charged sulfonate groups. This study was designed to evaluate the anticalcification effect of surface-modification of biologic arteries by direct coupling of PEO-SO3 after GA fixation and changes of calcification according to the implantation period through the quantitative investigation of the deposited calcium and phosphorous contents of the biologic arterial tissues in the canine circulatory implantation model. MATERIAL AND METHOD: Total of 16 fresh canine carotid arteries were harvested from eight adult dogs and divided in to GA group(n =8) and PEO-SO3 group(n=8). Sulfonation of diamino-terminated PEO was performed using propane sultone. Canine carotid arteries were only crosslinked with 0.65% GA solution in GA group and modified by direct coupling 5% PEO-SO3 solution after GA crosslinkage for 2 days and stabilized by NaBH4 solution for 16 hours in PEO-SO3 group. In both groups the resected segment of bilateral carotid arteries were reconstructed. Reconstructed segments of the two groups were analysed the quantities of calcium and phosphorous contents after 3(n=4) and 6(n=4) weeks in vivo. RESULT: After implantation of 3 seeks, PEO-SO3 group showed significantly less depositions.

Development of Calcification-Resistant Bovine Pericardium with PEO-SO3 (I): An implantation study of bovine pericardium at aorta and pulmonary artery in canine model / 대한흉부외과학회지

BACKGROUND: Calcific degeneration is unavoidable in either homo or heterografts implanted in the human body. We have developed a calcification-resistant cardiovascular tissue patch using a novel technique of anticalcification. MATERIALS AND METHODS: Fresh bovine pericardium was harvested at the slaughter house and transfered to the laboratory in Hank's solution. After trimming and fixing the pericardium, it was embedded in 4degree C 0.65% glutaraldehyde for a week and then washed by phosphate-buffered saline (PBS) of pH 7.4. This prepared pericardium was then stored in 2.5% sulphonated polyethyleneoxide (PEO-SO3) solution for 2 days at room temperature and reversed by 4degree C NaBH4 solution for 16 hours. To evaluate the calcification-resistance of surface modified bovine pericardium with PEO-SO3, either glutaraldehyde-treated (GA group, n=4) or PEO-SO3-treated pericardial patch (PEO-SO3 group, n=4) was implanted into adult mongrel dog to reconstruct the main pulmonary artery and the descending aorta using a partial clamp technique. After 1 month follow-up, the implanted patches were retrieved to evaluate the pathologic findings and the content of calcium and phosphorous. RESULTS: The PEO-SO3 group showed substantially less retraction and significantly less calcium deposition than the GA group in both aortic (7.10+/-1.05 vs. 13.81+/-2.33 mg/g of dried tissue) and pulmonary positions (1.55+/-0.29 vs. 6.72+/-0.70 mg/g) (p<0.01). Phosphorous contents were also less in the PEO-SO3 group than the GA group significantly, 8.11+/-1.07 mg/g vs. 19.33+/-4.31 mg/g in the aortic and 2.58+/-0.40 vs. 12.60+/-3.40 mg/g in thepulmonary position (p<0.01). CONCLUSIONS: These findings suggest that PEO-SO3 modified bovine pericardium is highly calcification-resistant but further study is needed to evaluate the long-term biological safety and compatibility of the prosthesis.

Development of Calcification-resistant Bovine Pericardium with PEO-SO3 (II): An implantation study of bovine pericardium at artery and peritoneum / 대한흉부외과학회지

BACKGROUND: Calcific degeneration limits durabilities of the bioprosthetic tissues implanted in the human body. The direct coupling sulphonated polyethyleneoxide (PEO-SO3) to the bioprosthetic tissues after glutaraldehyde (GA) fixation and the removal of residual aldehyde groups from the tissues can augment the effect of calcification-resistance. MATERIALS AND METHODS: To study the anti-calcification effect by PEO-SO3 modification and the removal of the residual aldehyde groups of tissues, surface modified bovine pericardia (BP-PEO-SO3) were preserved in aseptic saline to wash out GA (saline group) and 0.65% GA solution (GA group). And then above two groups and PERIGUARD (Bio-vascular. Co.) (product group) were evaluated with respects to calcium contents and microscopic findings using in vivo implantation models at carotid and femoral artery and peritoneum of 8 adult dogs. RESULTS: In the tissues retrieved from carotid artery, calcium content was significantly decreased in saline group than in other two groups (saline; 2.89+/-0.31 vs. GA; 6.14+/-1.08 vs. product; 22.82+/-5.00 mg/g of dried tissue; p<0.05). In the tissues retrieved from femoral artery and peritoneum, calcium amount was also decreased in saline group than in other two groups, but not reached the significant difference between groups. On the other hand, the pathologic findings of pericardial tissues showed marked destructuction in GA group compared to the other two groups. CONCLUSIONS: In this study, covalently PEO-SO3 bound to bovine pericardium decreased calcifications and the anti-calcification effect of BP-PEO-SO3 could be augmented by the washing out the residual aldehyde groups using saline after GA fixation. Conclusively, the PEO-SO3 modified bovine pericardium is highly resistant to calcification and can be useful for the development of calcification-resistant cardiovascular patches and valves.