Development of Calcification-resistant Bovine Pericardium with PEO-$SO_3(II)$ -An implantation study of bovine pericardium at artery and peritoneum-

PEO-$SO_3$를 이용한 항석회화 조직첨포의 개발(II) -동맥과 복막 이식 실험연구-

  • 김형묵 (고려대학교 의과대학 흉부외과학 교실) ;
  • 백만종 (고려대학교 의과대학 흉부외과학 교실) ;
  • 김광택 (고려대학교 의과대학 흉부외과학 교실) ;
  • 이인성 (고려대학교 의과대학 흉부외과학 교실) ;
  • 김학제 (고려대학교 의과대학 흉부외과학 교실) ;
  • 이원규 (한국과학기술원 고분자화학 연구소) ;
  • 박기동 (한국과학기술원 고분자화학 연구소)
  • Published : 1998.11.01

Abstract

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.

연구배경 : 인체내 이식된 생체조직들은 석회화 변성으로 인해 그 내구성이 단축된다. 이러한 조직들을 이식하기전에 글루타르알데하이드(GA)로 고정후 sulphonated polyethyleneoxide(PEO-SO3)를 결합시키고 또한 조직내 의 잔유 알데히드기를 제거함으로써 석회화에 대한 내구성을 향상시킬 수 있다 재료 및 방법 : PEO-SO3 처리법과 잔유 알데히드기 제거의 석회화 방지 효과를 알아보기 위하여 GA 고정 후 PEO-SO3로 처리한 소 심낭 첨포를 잔유 알데히드기 제거를 위해 무균 생리식염수에 보존한 saline 군과 0.65% GA 용액 에 보존한 GA군, 그리고 이미 상품화되어 임상에서 사용되고 있는 product군을 8마리 개의 경동맥과 대퇴동 맥 및 복막에 이식하여 6주 후 적출하여 칼슘량 및 병리조직 소견에 대해 알아보았다. 결과 : 경동맥에서 채취한 조직첨포의 칼슘량은 saline군에서 GA군과 product군에 비해 유의하게 적었다 (saline; 2.89$\pm$0.31 vs. GA; 6.14$\pm$1.08 vs. product; 22.82$\pm$5.00 mg/g; p< .05). 대퇴동맥과 복막 이식 첨포에서의 칼슘량 또한 saline군에서 다른 두 군에 비해 가장 적었으나 통계적인 유의성은 없었다. 한편 병리조직 검사에서는 GA군에서 다른 두 군에 비해 조직의 석회화로 인한 변성 파괴가 심하였다. 결론 : 본 연구에서 소 심낭 조직 첨포와 결합한 PEO-SO3는 석회화를 감소시키고 또한 조직내 잔유 알데히드기 를 생리식염수로 세척하여 제거함으로써 항석회화 효과를 증가시킬 수 있었다. 결론적으로 PEO-SO3로 처리한 소 심낭 조직은 석회화 변성에 대한 강한 저항성을 보임으로써 심혈관 첨포나 인공 조직 판막 개발 에 도움를 줄 수 있을 것이다.

Keywords

References

  1. CRC Crit Rev Biocomp v.2 Bioprosthetic heart valve calcification: Clinical features, pathology, and prospects for prevention Levy RJ;Schoen FJ;Golomb G
  2. J Biomed Mater Res v.22 Biomaterial associated calcification: Pathology, mechanisms, and strategies for prevention Schoen FJ;Harasaki H;Kim K(et al.)
  3. J Biomed Mater Res v.21 Cardiac valve prostheses: Review of clinical status and contemporary biomaterials issues Schoen FJ
  4. Am J Pathol v.122 Calcification of subcutaneously implanted type I collagen sponges: Effects of formaldehyde and glutaraldehyde pretreatments Levy RJ;Schoen FJ;Sherman FS(et al.)
  5. Am J Cardiol v.52 Mechanism of calcification of porcine bioprosthetic aortic valve susp: Role of T-lymphocytes Levy RJ;Schoen FJ;Howard SL
  6. J Thorac Cardivasc Surg v.86 Role of mechanical stress in calcification of aortic bioprothetic valve Thubrikar MJ;Deck DJ;Aoud J
  7. Atherosclerosis v.46 The identification of the vitamine K dependent bone protein, osteocalcin as one of the gamma-carboxyglutamic acid containing proteins present in calcified atherosclerotic plaque Levy RJ;Gundberg C;Scheinman R
  8. Int J Pharmaceut v.52 Controlled release of 1-hydroxyethylidene diphosphonate: in vitro assessment and effects on bioprosthetic calcification in sheep tricuspid valve replacement Johnston TP;Bove EL;Bolling SF(et al.)
  9. Am J Pathol v.141 Calcification of allograft aortic wall in a subdermal model: pathophysiology and inhibition by A13+ and aminodiphos phonate preincubations Webb CL;Nguyen NM;Schoen FJ;Levy RJ
  10. J Biomed Mater Res v.27 Inhibition of calcification of glutaraldehyde pretreated porcine aortic valve cusps with sodium dodecyl sulfate: preincubation and controlled release studies Hirsch D;Drader J;Thomas TJ;Schoen FJ;Levy JT;Levy RJ
  11. Circulation v.90 Mechanism of efficacy of 2-amino oleic acid for inhibition of calcification of glutaradehyde pretreated porcine bioprosthetic heart valves Chen W;Schoen FJ;Levy RJ
  12. J Biomed Mater Res v.21 Chemically modified collagen: a natural biomaterial for tissue replacement Nimni MN;Cheung D;Strates B(et al.)
  13. Biomaterials v.15 Anticalcification treatment of pericardial prostheses Chanda J
  14. J Biomed Mater Res v.24 Effect of alternative crosslinking methods on the low strain rate viscoelastic properties of bovine pericardial bioprosthetic material Pereira CA;Lee JM;Haberer SA
  15. Trans Am Soc Artif Intern Organs v.27 LVAD mineralization of gamma carboxyglutamic acid containing proteins in normal and pathologically manetalized tissue Harasaki H;Moritz A;Uchida N(et al.)
  16. J Biomed Mater Res v.25 Negative cilia concept for thromboresistance: synergistic effect of PEO and sulfonated groups grafted onto polyurethanes Han DK;Jeong SY;Kim YH(et al.)
  17. PU-PEO-SO₃ J Biomed Mater Res v.27 In vivo biostability and calcification-resistance of surface-modified Han DK;Park KD;Jeong SY(et al.)
  18. PU-PEO-SO₃ASAIO J v.39 In vivo canine studies of a sinkhole valve and vascular graft coated with biocompatible Han DK;Park KD;Jeong SY(et al.)
  19. 대흉외지 v.31 PU-PEO-SO₃를 이용한 항석회화 조직첨포의 개발(Ⅰ) - 잡견을 이용한 대동맥과 폐동맥 이식 실험연구 - 김형묵;백만종;선경등
  20. ASAIO J v.40 Chemical modification of implantable biological tissue for anti-calcification Park KD;Yun JY;Han DK;Kim YH;Kim HM;Kim KT
  21. Trans Soc Biomater v.14 Polyactive: a bone-bonding polymer effect of PEO/PBT proportion Blitterswijk CA;Brink J;Leenders H;Hesseling SC;Bakker D
  22. Biomaterials v.18 Novel anti-calcification treatment of biological tissues by grafting of suphonated poly(ethylene oxide) Park KD;Lee WK;Yun JY(et al.)