Anticoagulant Ability and Heparinization of Decellularized Biomaterial Scaffolds_Journal of Biomedical Engineering

Authors：

BAOJi ^1,2 , SUNJiu ^3,4 , ZHOUYongjie ¹ , WUQiong ¹ , WANGYujia ¹ , LILi ¹ , JIANGXin ⁵ , MALang ⁵ , XIEMingjun ^3,4 , SHIYujun ¹ ,  BUHong ^1,2

1. Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu 610041, China;
2. Department of Pathology, West China Hospital, Sichuan University, Chengdu 610041, China;
3. Department of General Surgery, The First People's Hospital of Yibin, Yibin 644000, China;
4. Department of Clinical Medicine, Luzhou Medical College, Luzhou 646000, China;
5. College of Polymer Science and Engineering, Sichuan University, Chengdu, 610065, China;

Corresponding author：

BUHong, Email: hongbu@scu.edu.cn

Keywords：

decellarization; biomaterial; heparinization; anticoagulation

DOI：

10.7507/1001-5515.20150108

Video：

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In order to enhance the anticoagulant properties of decellularized biological materials as scaffolds for tissue engineering research via heparinized process, the decellularized porcine liver scaffolds were respectively immobilized with heparin through layer-by-layer self-assembly technique (LBL), multi-point attachment (MPA) or end-point attachment (EPA). The effects of heparinization and anticoagulant ability were tested. The results showed that the three different scaffolds had different contents of heparin. All the three kinds of heparinized scaffolds gained better performance of anticoagulant than that of the control scaffold. The thrombin time (TT), prothrombin time (PT) and activated partial thromboplastin time (APTT) of EPA scaffold group were longest in all the groups, and all the three times exceeded the measurement limit of the instrument. In addition, EPA scaffolds group showed the shortest prepared time, the slowest speed for heparin release and the longest recalcification time among all the groups. The decellularized biological materials for tissue engineering acquire the best effect of anticoagulant ability in vitro via EPA heparinized technique.

Citation： BAOJi, SUNJiu, ZHOUYongjie, WUQiong, WANGYujia, LILi, JIANGXin, MALang, XIEMingjun, SHIYujun, BUHong. Anticoagulant Ability and Heparinization of Decellularized Biomaterial Scaffolds. Journal of Biomedical Engineering, 2015, 32(3): 594-598. doi: 10.7507/1001-5515.20150108 Copy

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2.	VON SEGESSER L, JORNOD N, FAIDUTTI B. Repeat sternotomy after reconstruction of the pericardial sac with glutaraldehyde-preserved equine pericardium[J]. J Thorac Cardiovasc Surg, 1987, 93(4):616-619.
3.	ARAÚJO J D, BRAILE D M, AZENHA FILHO J O, et al. The use of bovine pericardium as an arterial graft. A 5-year follow-up[J]. J Cardiovasc Surg (Torino), 1987, 28(4):434-439.
4.	ZEHE C, ENGLING A, WEGEHINGEL S, et al. Cell-surface heparan sulfate proteoglycans are essential components of the unconventional export machinery of FGF-2[J]. Proc Natl Acad Sci U S A, 2006, 103(42):15479-15484.
5.	BAO Ji, SHI Yujun, SUN Huaiqiang, et al. Construction of a portal implantable functional tissue-engineered liver using perfusion-decellularized matrix and hepatocytes in rats[J]. Cell Transplant, 2011, 20(5):753-766.
6.	WANG Xuening, CHEN Changzhi, YANG Min, et al. Implantation of decellularized small-caliber vascular xenografts with and without surface heparin treatment[J]. Artif Organs, 2007, 31(2):99-104.
7.	TSAI C C, CHANG Y, SUNG H W, et al. Effects of heparin immobilization on the surface characteristics of a biological tissue fixed with a naturally occurring crosslinking agent (genipin):an in vitro study[J]. Biomaterials, 2001, 22(6):523-533.
8.	刘秀英, 张超灿, 徐卫林.甲苯胺蓝分光光度法测定肝素钠的研究[J].化学试剂, 2009, 31(4):271-274.
9.	LU Qiang, ZHANG Shenjia, HU Kun, et al. Cytocompatibility and blood compatibility of multifunctional fibroin/collagen/heparin scaffolds[J]. Biomaterials, 2007, 28(14):2306-2313.
10.	LV Qiang, CAO Chuanbao, ZHU Hesun. A novel solvent system for blending of polyurethane and heparin[J]. Biomaterials, 2003, 24(22):3915-3919.
11.	RAN Fen, NIE Shengqiang, LI Jie, et al. Heparin-like macromolecules for the modification of anticoagulant biomaterials[J]. Macromol Biosci, 2012, 12(1):116-125.
12.	李沁华, 邹翰.类肝素聚乙烯醇复合材料抗凝血性能的研究[J].中国生物医学工程学报, 1999, 18(1):15-21.
13.	李燕梅, 黄亚东, 王为, 等.酸性成纤维细胞生长因子/胶原蛋白复合海绵的研制及其组织相容性[J].生物医学工程学杂志, 2008, 25(3):578-583.
14.	NIMNI M E, CHEUNG D, STRATES B, et al. Chemically modified collagen:a natural biomaterial for tissue replacement[J]. J Biomed Mater Res, 1987, 21(6):741-771.
15.	高宁国, 程秀兰, 杨敬, 等.肝素结构与功能的研究进展[J].生物工程进展, 1999, 19(5):4-13.
16.	AMIJI M, PARK K. Surface modification of polymeric biomaterials with poly(ethylene oxide), albumin, and heparin for reduced thrombogenicity[J]. J Biomater Sci Polym Ed, 1993, 4(3):217-234.
17.	DESAI U R, PETITOU M, BJ?RK I, et al. Mechanism of heparin activation of antithrombin:role of individual residues of the pentasaccharide activating sequence in the recognition of native and activated states of antithrombin[J]. J Biol Chem, 1998, 273(13):7478-7487.

1. GABBAY S, BORTOLOTTI U, WASSERMAN F, et al. Long-term follow-up of the Ionescu-Shiley mitral pericardial xenograft[J]. J Thorac Cardiovasc Surg, 1984, 88(5 Pt 1):758-763.
2. VON SEGESSER L, JORNOD N, FAIDUTTI B. Repeat sternotomy after reconstruction of the pericardial sac with glutaraldehyde-preserved equine pericardium[J]. J Thorac Cardiovasc Surg, 1987, 93(4):616-619.
3. ARAÚJO J D, BRAILE D M, AZENHA FILHO J O, et al. The use of bovine pericardium as an arterial graft. A 5-year follow-up[J]. J Cardiovasc Surg (Torino), 1987, 28(4):434-439.
4. ZEHE C, ENGLING A, WEGEHINGEL S, et al. Cell-surface heparan sulfate proteoglycans are essential components of the unconventional export machinery of FGF-2[J]. Proc Natl Acad Sci U S A, 2006, 103(42):15479-15484.
5. BAO Ji, SHI Yujun, SUN Huaiqiang, et al. Construction of a portal implantable functional tissue-engineered liver using perfusion-decellularized matrix and hepatocytes in rats[J]. Cell Transplant, 2011, 20(5):753-766.
6. WANG Xuening, CHEN Changzhi, YANG Min, et al. Implantation of decellularized small-caliber vascular xenografts with and without surface heparin treatment[J]. Artif Organs, 2007, 31(2):99-104.
7. TSAI C C, CHANG Y, SUNG H W, et al. Effects of heparin immobilization on the surface characteristics of a biological tissue fixed with a naturally occurring crosslinking agent (genipin):an in vitro study[J]. Biomaterials, 2001, 22(6):523-533.
8. 刘秀英, 张超灿, 徐卫林.甲苯胺蓝分光光度法测定肝素钠的研究[J].化学试剂, 2009, 31(4):271-274.
9. LU Qiang, ZHANG Shenjia, HU Kun, et al. Cytocompatibility and blood compatibility of multifunctional fibroin/collagen/heparin scaffolds[J]. Biomaterials, 2007, 28(14):2306-2313.
10. LV Qiang, CAO Chuanbao, ZHU Hesun. A novel solvent system for blending of polyurethane and heparin[J]. Biomaterials, 2003, 24(22):3915-3919.
11. RAN Fen, NIE Shengqiang, LI Jie, et al. Heparin-like macromolecules for the modification of anticoagulant biomaterials[J]. Macromol Biosci, 2012, 12(1):116-125.
12. 李沁华, 邹翰.类肝素聚乙烯醇复合材料抗凝血性能的研究[J].中国生物医学工程学报, 1999, 18(1):15-21.
13. 李燕梅, 黄亚东, 王为, 等.酸性成纤维细胞生长因子/胶原蛋白复合海绵的研制及其组织相容性[J].生物医学工程学杂志, 2008, 25(3):578-583.
14. NIMNI M E, CHEUNG D, STRATES B, et al. Chemically modified collagen:a natural biomaterial for tissue replacement[J]. J Biomed Mater Res, 1987, 21(6):741-771.
15. 高宁国, 程秀兰, 杨敬, 等.肝素结构与功能的研究进展[J].生物工程进展, 1999, 19(5):4-13.
16. AMIJI M, PARK K. Surface modification of polymeric biomaterials with poly(ethylene oxide), albumin, and heparin for reduced thrombogenicity[J]. J Biomater Sci Polym Ed, 1993, 4(3):217-234.
17. DESAI U R, PETITOU M, BJ?RK I, et al. Mechanism of heparin activation of antithrombin:role of individual residues of the pentasaccharide activating sequence in the recognition of native and activated states of antithrombin[J]. J Biol Chem, 1998, 273(13):7478-7487.

Journal of Biomedical Engineering

Anticoagulant Ability and Heparinization of Decellularized Biomaterial Scaffolds

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