EFFECT OF SUSTAINED-RELEASE BASIC FIBROBLAST GROWTH FACTOR ON HEALING OF BILE DUCT DEFECT IN PIGS_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

TAO Liang ¹ , LI Qiang ¹ , REN Haozhen ¹ , DAI Jianwu ² , DING Yitao ¹

1Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing Jiangsu, 210008, P.R.China;;
2Institute of Genetics and Developmental Biology, Chinese Academy of Sciences. Corresponding author: DING Yitao, E-mail: yitaoding@hotmail.com;

Corresponding author：

Keywords：

Tissue engineering; Bile duct defect; Sustained-release basic fribroblast growth factor; Collagen; Microvessel density; Pig

DOI：

10.7507/1002-1892.20130046

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the effects of sustained-release basic fibroblast growth factor (bFGF) on healing of bile duct defect. Methods A model of bile duct wall defect (2 cm in length and 1/3-2/3 of the bile duct circumference in width) was made in 24 pigs (male or female, weighing 15-30 kg), and then defect was repaired with sustained-release bFGF collagen membrane (2.0 cm × 1.0 cm × 0.5 cm in size) in the experimental group (n=12) or with collagen membrane (2.0 cm × 1.0 cm × 0.5 cm in size) alone in the blank control group (n=12). Another 4 healthy pigs were used to obtain normal bile duct as normal control group. The survival condition of pigs was observed after operation; at 1, 2, and 3 months after operation, the blood sampling was collected to test the changes of liver function, and the bile duct specimens were harvested to count the microvessel density (MVD) and submucosal gland by HE staining and immunohistochemistry staining; and at 3 months after operation, cholangiography examination was done. Results All the animals survived to completion of the experiment. Intra-abdominal adhesion was serious in the experimental and blank control groups at 1 week after operation, but the adhesion was markedly improved in the experimental group when compared with the blank control group with time passing. The liver function test showed that alkaline phosphatase in the experimental group was significantly lower than that in the blank control group at 2 and 3 months (P lt; 0.05), but no significant difference in aspartate aminortransferase, total bilirubin, and albumin was found among 3 groups (P gt; 0.05). The histology and immunohistochemistry staining observations showed that the regeneration rates of submucosal glands and epithelium in the experimental group were faster than those in the blank control group; defect was covered with the epithelium at 2 months, and the structure was similar to that of normal control group at 3 months; and the edema and inflammation infiltration were reduced when compared with the blank control group. The counts of MVD and submucosal gland were significantly higher than those in blank control group and normal control group at 1 month after operation (P lt; 0.05), and then decreased and remained at normal levels at 2 months after operation. There was a positive correlation between submucosal gland counting and MVD counting in 3 groups after operation (P lt; 0.01). The cholangiography examination showed no biliary dilatation or cholelithiasis after 3 months in experimental group and blank control group. Conclusion Sustained-release bFGF can promote healing of bile duct defect by accelerating the vascularization, gland regeneration, and epithelialization.

Citation： TAO Liang,LI Qiang,REN Haozhen,DAI Jianwu,DING Yitao. EFFECT OF SUSTAINED-RELEASE BASIC FIBROBLAST GROWTH FACTOR ON HEALING OF BILE DUCT DEFECT IN PIGS. Chinese Journal of Reparative and Reconstructive Surgery, 2013, 27(2): 212-218. doi: 10.7507/1002-1892.20130046 Copy

1.	Shimono K, Nosé Y. The need to develop artificial bile ducts. Artif Organs, 1995, 19(2): 115-116.
2.	陶亮, 李强, 丁义涛. 可降解胆管修复材料的研究进展. 中华肝胆外科杂志, 2011, 17 (9): 788-790.
3.	窦春青, 周宁新. 组织工程化人工胆管材料学研究进展. 解放军医学杂志, 2007, 32(3): 276-277.
4.	Ornitz DM, Iton N. Fibroblast growth factors. Grnome Biol, 2001, 2(2): REVIEWS3005.
5.	Nakamura S, Nambu M, Ishizuka T, et al. Effect of controlled release of fibroblast growth factor-2 from chitosan/fucoidan micro complex-hydrogel on in vitro and in vivo vascularization. J Biomed Mater Res A, 2008, 85(3): 619-627.
6.	徐勇, 耿智敏, 王居邠. 碱性成纤维细胞生长因子对胆肠吻合口愈合的影响. 中国修复重建外科杂志, 2005, 19(5): 341-343.
7.	Nagase T, Hisatomi T, Koshima I, et al. Heterotopic ossification in the sacral pressure ulcer treated with basic fibroblast growth factor: coincidence or side effect? J Plast Reconstr Aesthet Surg, 2007, 60(3): 327-329.
8.	李晓东, 孙文杰, 戴建武. 几种常用生长因子的基因工程与创面修复. 中华损伤与修复杂志(电子版), 2007, 2(1): 51-54.
9.	Zhao WX, Han Q, Lin H, et al. Improved neovascularization and wound repair by targeting human basic fibroblast growth factor (bFGF) to fibrin. J Mol Med (Berl), 2008, 86(10): 1127-1138.
10.	Weidner N. Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors. Breast Cancer Res Treat, 1995, 36(2): 169-180.
11.	Miyazawa M, Torii T, Toshimitsu Y, et al. A tissue engineered artificial bile duct grown to resemble the native bile duct. Am J Transplant, 2005, 5(6): 1541-1547.
12.	Aikawa M, Miyazawa M, Okamoto K, et al. A novel treatment for bile duct injury with a tissue-engineered bioabsorbable polymer patch. Surgery, 2010, 147(4): 575-580.
13.	Rosen M, Ponsky J, Petras R, et al. Small intestinal submucosa as a bioscaffold for biliary tract regeneration. Surgery, 2002, 132(3): 480-486.
14.	Gómez NA, Zapatier JA, Vargas PE. Re: “Small intestinal submucosa as a bioscaffold for biliary tract regeneration”. Surgery, 2004, 135(4): 460.
15.	Ismail A, Ramsis R, Sherif A, et al. Use of human amniotic stem cells for common bile duct reconstruction: vascularized support of a free amnion graft. Med Sci Monit, 2009, 15(9): BR243-247.
16.	Nakashima S, Nakamura T, Miyagawa K, et al. In situ tissue engineering of the bile duct using polypropylene mesh-collagen tubes. Int J Artif Organs, 2007, 30(1): 75-85.
17.	Nakashima S, Nakamura T, Han L, et al. Experimental biliary reconstruction with an artificial bile duct using in situ tissue engineering technique. Inflammation and Regeneration, 2007, 27(6): 579-585.
18.	Sun W, Sun C, Lin H, et al. The effect of collagen-binding NGF-beta on the promotion of sciatic nerve regeneration in a rat sciatic nerve crush injury model. Biomaterials, 2009, 30(27): 4649-4656.
19.	Chen W, Shi C, Yi S, et al. Bladder regeneration by collagen scaffolds with collagen binding human basicfi broblast growth factor. J Urol, 2010, 183(6): 2432-2439.
20.	Shi C, Chen W, Zhao Y, et al. Regeneration of full-thickness abdominal wall defects in rats using collagen scaffolds loaded with collagen-binding basic fibroblast growth factor. Biomaterials, 2011, 32(3): 753-759.
21.	Li X, Sun H, Lin N, et al. Regeneration of uterine horns in rats by collagen scaffolds loaded with collagen-binding human basic fibroblast growth factor. Biomaterials, 2011, 32(32): 8172-8181.

1. Shimono K, Nosé Y. The need to develop artificial bile ducts. Artif Organs, 1995, 19(2): 115-116.
2. 陶亮, 李强, 丁义涛. 可降解胆管修复材料的研究进展. 中华肝胆外科杂志, 2011, 17 (9): 788-790.
3. 窦春青, 周宁新. 组织工程化人工胆管材料学研究进展. 解放军医学杂志, 2007, 32(3): 276-277.
4. Ornitz DM, Iton N. Fibroblast growth factors. Grnome Biol, 2001, 2(2): REVIEWS3005.
5. Nakamura S, Nambu M, Ishizuka T, et al. Effect of controlled release of fibroblast growth factor-2 from chitosan/fucoidan micro complex-hydrogel on in vitro and in vivo vascularization. J Biomed Mater Res A, 2008, 85(3): 619-627.
6. 徐勇, 耿智敏, 王居邠. 碱性成纤维细胞生长因子对胆肠吻合口愈合的影响. 中国修复重建外科杂志, 2005, 19(5): 341-343.
7. Nagase T, Hisatomi T, Koshima I, et al. Heterotopic ossification in the sacral pressure ulcer treated with basic fibroblast growth factor: coincidence or side effect? J Plast Reconstr Aesthet Surg, 2007, 60(3): 327-329.
8. 李晓东, 孙文杰, 戴建武. 几种常用生长因子的基因工程与创面修复. 中华损伤与修复杂志(电子版), 2007, 2(1): 51-54.
9. Zhao WX, Han Q, Lin H, et al. Improved neovascularization and wound repair by targeting human basic fibroblast growth factor (bFGF) to fibrin. J Mol Med (Berl), 2008, 86(10): 1127-1138.
10. Weidner N. Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors. Breast Cancer Res Treat, 1995, 36(2): 169-180.
11. Miyazawa M, Torii T, Toshimitsu Y, et al. A tissue engineered artificial bile duct grown to resemble the native bile duct. Am J Transplant, 2005, 5(6): 1541-1547.
12. Aikawa M, Miyazawa M, Okamoto K, et al. A novel treatment for bile duct injury with a tissue-engineered bioabsorbable polymer patch. Surgery, 2010, 147(4): 575-580.
13. Rosen M, Ponsky J, Petras R, et al. Small intestinal submucosa as a bioscaffold for biliary tract regeneration. Surgery, 2002, 132(3): 480-486.
14. Gómez NA, Zapatier JA, Vargas PE. Re: “Small intestinal submucosa as a bioscaffold for biliary tract regeneration”. Surgery, 2004, 135(4): 460.
15. Ismail A, Ramsis R, Sherif A, et al. Use of human amniotic stem cells for common bile duct reconstruction: vascularized support of a free amnion graft. Med Sci Monit, 2009, 15(9): BR243-247.
16. Nakashima S, Nakamura T, Miyagawa K, et al. In situ tissue engineering of the bile duct using polypropylene mesh-collagen tubes. Int J Artif Organs, 2007, 30(1): 75-85.
17. Nakashima S, Nakamura T, Han L, et al. Experimental biliary reconstruction with an artificial bile duct using in situ tissue engineering technique. Inflammation and Regeneration, 2007, 27(6): 579-585.
18. Sun W, Sun C, Lin H, et al. The effect of collagen-binding NGF-beta on the promotion of sciatic nerve regeneration in a rat sciatic nerve crush injury model. Biomaterials, 2009, 30(27): 4649-4656.
19. Chen W, Shi C, Yi S, et al. Bladder regeneration by collagen scaffolds with collagen binding human basicfi broblast growth factor. J Urol, 2010, 183(6): 2432-2439.
20. Shi C, Chen W, Zhao Y, et al. Regeneration of full-thickness abdominal wall defects in rats using collagen scaffolds loaded with collagen-binding basic fibroblast growth factor. Biomaterials, 2011, 32(3): 753-759.
21. Li X, Sun H, Lin N, et al. Regeneration of uterine horns in rats by collagen scaffolds loaded with collagen-binding human basic fibroblast growth factor. Biomaterials, 2011, 32(32): 8172-8181.

Previous Article
APPLICATION OF PKH26 LABELING COMBINED WITH IN VIVO IMAGING TECHNOLOGY IN INTERVERTEBRAL DISC TISSUE ENGINEERING
Next Article
PROGRESS ON CELL INFILTRATION IN ELECTROSPUN SCAFFOLD

Chinese Journal of Reparative and Reconstructive Surgery

EFFECT OF SUSTAINED-RELEASE BASIC FIBROBLAST GROWTH FACTOR ON HEALING OF BILE DUCT DEFECT IN PIGS

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content