$PEO-SO_3$를 이용한 항석회화 조직첨포의 개발 (I) - 잡견을 이용한 대동맥과 폐동맥 이식 실험연구 -

Development of Calcification-Resistant Bovine Pericardium with $PEO-SO_3$ (I) - An implantation study of bovine pericardium at aorta and pulmonary artery in canine model -

  • 김형묵 (고려대학교 의과대학 흉부외과학 교실) ;
  • 백만종 (고려대학교 의과대학 흉부외과학 교실) ;
  • 선경 (인하대학교 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)
  • Kim, Hyoung-Mook (Department of Thoracic & cardiovascular Surgery, Korea University, College of Medicine) ;
  • Baek, Man-Jong (Department of Thoracic & cardiovascular Surgery, Korea University, College of Medicine) ;
  • Sun, Kyung (Department of Thoracic & cardiovascular Surgery, Inha University, College of Medicine) ;
  • Kim, Kwang-Taik (Department of Thoracic & cardiovascular Surgery, Korea University, College of Medicine) ;
  • Lee, In-Sung (Department of Thoracic & cardiovascular Surgery, Korea University, College of Medicine) ;
  • Kim, Hark-Jei (Department of Thoracic & cardiovascular Surgery, Korea University, College of Medicine) ;
  • Lee, Won-Kyu (Polymer Chemistry Laboratory, Korea Institute of Science and Technology) ;
  • Park, Ki-Dong (Polymer Chemistry Laboratory, Korea Institute of Science and Technology)
  • 발행 : 1998.10.01

초록

연구배경: 인체에 이식된 동종 혹은 이종조직은 궁극적으로 석회화 변성이 일어난다. 저자들은 독자적인 항석회화 처리법을 이용해 석회화에 내구성을 가진 심혈관용 조직첨포를 개발하였다. 재료 및 방법:도축장에서 채취한 신선한 소의 심막을 Hank 용액에 담아 실험실로 이송하였다. 불필요한 부분을 절제해 낸 심낭조직을 0.65% glutaraldehyde 용액(4$^{\circ}C$)에 1주일 동안 저장한 다음 phophate-buffered saline 용액(pH 7.4)로 세척하였다. 이후 2.5% 술폰산화 폴리에틸렌옥사이드(PEO-SO3) 용액으로 실온에서 2일 동안 처리한 다음 4$^{\circ}C$ NaBH4용액으로 16시간 동안 환원시켰다. 실험은 글루타르알데하이드 용액으로만 처리한 심막첨포와 항석회화 처리된 심막첨포를 각각 대조군(GA군, n=4)과 실험군(PEO-SO3군, n=4)으로 나누어 혈관벽에 이식하여 석회화 변성 정도를 비교하였다. 실험모델은 성견의 폐동맥과 대동맥 벽의 일부를 절제한 후 심막첨포로 재건하는 방법을 이용하였고, 수술 후 평균 1개월 째에 이식된 첨포를 적출하여 조직병리 변화와 칼슘 및 인 함량을 측정하였다. 결과: 실험군이 대조군에 비해 조직 위축 변성, 칼슘(폐동맥; 1.55$\pm$0.29 vs. 6.72$\pm$0.70 mg/g, 대동맥; 7.10$\pm$1.05 vs. 13.81$\pm$2.33 mg/g) 및 인의 침착량 (폐동맥; 2.58$\pm$0.40 vs. 12.60$\pm$3.40 mg/g, 대동맥; 8.11$\pm$1.07 mg/g vs. 19.33$\pm$4.31 mg/g)이 현저하게 적었다 (P<0.01). 결론:이상의 결과에서 PEO-SO$_3$로 처리한 조직첨포는, 비록 단기관찰 결과이지만, 충분한 석회화 내성을 보이며 이 조직첨포의 장기적인 안정성과 적합성에 대해서는 계속적인 연구가 필요할 것이다.

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 4$^{\circ}C$ 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 4$^{\circ}C$ 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$\pm$1.05 vs. 13.81$\pm$2.33 mg/g of dried tissue) and pulmonary positions(1.55$\pm$0.29 vs. 6.72$\pm$0.70 mg/g)(p<0.01). Phosphorous contents were also less in the PEO-SO3 group than the GA group significantly, 8.11$\pm$1.07 mg/g vs. 19.33$\pm$4.31 mg/g in the aortic and 2.58$\pm$0.40 vs. 12.60$\pm$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.

키워드

참고문헌

  1. J Biomed Mater Res v.22 Biomaterial- associated calcification: Pathology, mechanisms, and strategies for prevention Schoen FJ;Harasaki H;Kim K(et al.)
  2. 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
  3. 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.)
  4. J Biomed Mater Res v.27 In vivo biostability and calcification-resistance of surface-modified PU-PEO-SO₃ Han DK;Park KD;Jeong SY(et al.)
  5. ASAIO J v.39 In vivo canine studies of a sinkhole valve and vascular graft coated with biocompatible PU-PEO-SO₃ Han DK;Park KD;Jeong SY(et al.)