Preparation and animal experiment of a novel sirolimus drug-coated mesh_West China Medical Journal

Authors：

SUN Jiajun ¹ ,  JI Zhenlin ¹ , HU Wanjun ² ,  ZHANG Zhigang ¹ , ZHANG Tianzhu ²

1. Second Department of General Surgery, Zhongda Hospital Affiliated to Southeast University, Nanjing, Jiangsu 210009, P. R. China;
2. School of Biological Science and Medical Engineering, Southeast University, Nanjing, Jiangsu 210096, P. R. China;

Corresponding author：

JI Zhenlin, Email: zhenlingji1@163.com; ZHANG Zhigang, Email: zhangzhigangseu@126.com

Keywords：

Hernia; Sirolimus; Polyethylene glycol dicarboxylic acid; Polypropylene mesh; Anti-blocking

DOI：

10.7507/1002-0179.201901197

Video：

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Objective To prepare a new sirolimus drug-coated polypropylene (SRL-PP) mesh by grafting he sirolimus onto the surface of the polypropylene (PP) mesh via chemical reaction, and to apply the new mesh to animal experiment to explore its anti-adhesion properties.Methods The sirolimus was grafted onto the surface of the mesh by chemical reaction to prepare the SRL-PP mesh, which was compared with the PP mesh and the polyethylene glycol modified polypropylene (PEG-PP) mesh. The three groups of meshes were respectively characterized (infrared spectroscopy test, contact angle measurement), and their tensile property was measured. These meshes were implanted into the abdominal cavity of the rats respectively. The anti-adhesion properties of the new sirolimus drug-coated mesh was studied by intraperitoneal adhesion and histopathological change in rats.Results The results of infrared spectrum analysis showed that there was a new absorption peak at the wavelength 1 643 cm^–1 (amide group) of SRL-PP mesh, suggesting that sirolimus drug was successfully uploaded onto the surface of the mesh; the SRL-PP mesh was excellent in hydrophilicity, which provided a favorable condition for the growth of peritoneal mesothelial cells. There was no significant difference in mechanical properties between SRL-PP mesh and PP mesh or PEG-PP mesh, which provided a good mechanical guarantee for clinical application. The degree of abdominal adhesion in SRL-PP mesh group (1.00±0.58) was significantly lower than that in PP mesh group (5.17±0.69) and PEG-PP mesh group (4.00±0.58), and the t_D value between SRL-PP mesh group and PP mesh group was 2.76 (P<0.05). The number of inflammatory cells and the expression of inflammatory cytokines in the adhesion tissue in SRL-PP mesh group were significantly lower than those in PP mesh group and PEG-PP mesh group.Conclusions The sirolimus is successfully loaded onto the surface in the PP mesh by chemical reaction. Animal experiment shows that the sirolimus drug-coated mesh can significantly reduce the abdominal adhesion of the rats, which provides a basis for clinical trial and application.

Citation： SUN Jiajun, JI Zhenlin, HU Wanjun, ZHANG Zhigang, ZHANG Tianzhu. Preparation and animal experiment of a novel sirolimus drug-coated mesh. West China Medical Journal, 2019, 34(6): 659-664. doi: 10.7507/1002-0179.201901197 Copy

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2.	Kingsnorth A, LeBlanc K. Hernias: inguinal and incisional. Lancet, 2003, 362(9395): 1561-1571.
3.	Kamel RM. Prevention of postoperative peritoneal adhesions. Eur J Obstet Gynecol Reprod Biol, 2010, 150(2): 111-118.
4.	Boland GM, Weigel RJ. Formation and prevention of postoperative abdominal adhesions. J Surg Res, 2006, 132(1): 3-12.
5.	Sahbaz A, Aynioglu O, Isik H, et al. Bromelain: a natural proteolytic for intra-abdominal adhesion prevention. Int J Surg, 2015, 14: 7-11.
6.	Coleman MG, McLain AD, Moran BJ. Impact of previous surgery on time taken for incision and division of adhesions during laparotomy. Dis Colon Rectum, 2000, 43(9): 1297-1299.
7.	Hosseini A, Akhavan S, Menshaei M, et al. Effects of streptokinase and normal saline on the incidence of intra-abdominal adhesion 1 week and 1 month after laparotomy in rats. Adv Biomed Res, 2018, 7: 16.
8.	Bryers JD, Giachelli CM, Ratner BD. Engineering biomaterials to integrate and heal: the biocompatibility paradigm shifts. Biotechnol Bioeng, 2012, 109(8): 1898-1911.
9.	Sadava EE, Krpata DM, Gao Y, et al. Wound healing process and mediators: implications for modulations for hernia repair and mesh integration. J Biomed Mater Res Part A, 2014, 102(1): 295-302.
10.	Poppas DP, Sung JJ, Magro CM, et al. Hydrogel coated mesh decreases tissue reaction resulting from polypropylene mesh implant: implication in hernia repair. Hernia, 2016, 20(4): 623-632.
11.	Scheidback H, Tamme C, Tannapfel A, et al. In vivo studies comparing the biocompatibility of various polypropylene meshes and their handling properties during endoscopic total extraperitoneal (TEP) patchplasty: an experimental study in pigs. Surg Endosc, 2004, 18(2): 211-220.
12.	Zhang Z, Zhang T, Li J,, et al. Preparation of poly( L-lactic acid) - modified polypropylene mesh and its antiadhesion in experimental abdominal wall defect repair. J Biome Mater Res B Appl Biomater, 2014, 102(1): 12-21.
13.	Laschke MW, Häufel JM, Roller J, et al. Rapamycin, but not cyclosporine A, inhibits vascularization and incorporation of implanted surgical meshes. Transpl Int, 2009, 22(6): 654-662.
14.	Shah PR, Kute VB, Patel HV, et al. Therapeutic drug monitoring of sirolimus. Clinical Queries: Nephrology, 2015, 4: 44-49.
15.	Dilling DF, Nair A, Gries CJ, et al. Use of sirolimus in patients with lymphangioleiomyomatosis (LAM) on waiting lists for lung transplant (LTX). J Heart Lung Transplant, 2018, 37(4): s457.
16.	Lai ZW, Kelly R, Winans T, et al. Sirolimus in patients with clinically active systemic lupus erythematosus resistant to, or intolerant of, conventional medications: a single-arm, open-label, phase 1/2 trial. Lancet, 2018, 391(10126): 1186-1196.
17.	任常, 朱兰. 盆腹腔手术后粘连的分类及评价方法. 中华妇产科杂志, 2012, 47(4): 317-318.
18.	Ye XL, Han XY, Wei B, et al. Ventral hernia repair in rat using nanofibrous polylactic acid/polypropylene meshes. Nanomedicine (Lond), 2018, 13(17): 2187-2199.
19.	Grant S, Ramshaw B. Progress in synthetic prosthetic mesh for ventral hernia repair//LeBlanc K, Kingsnorth A, Sanders D. Management of abdominal hernias. 5 ed. Springer, Cham, 2018: 173-178.
20.	Zhang C, Salick MR, Cordie TM, et al. Incorporation of poly(ethylene glycol) grafted cellulose nanocrystals in poly(lactic acid) electrospun nanocomposite fibers as potential scaffolds for bone tissue engineering. Mater Sci Eng C Mater Biol Appl, 2015, 49: 463-471.
21.	Kong CY, Lai LL, Khoo AYY, et al. Inflammatory reaction to fish oil coated polypropylene mesh used for laparoscopic incisional hernia repair: a case report. BMC Surg, 2016, 16: 8.
22.	Vermet G, Degoutin S, Chai F, et al. Cyclodextrin modified PLLA parietal reinforcement implant with prolonged antibacterial activity. Acta Biomater, 2017, 53: 222-232.
23.	Bayhan Z, Zeren S, Kocak FE, et al. Antiadhesive and anti-inflammatory effects of pirfenidone in postoperative intra-abdominal adhesion in an experimental rat model. J Surg Res, 2016, 201(2): 348-355.
24.	宋宇, 张慧, 刘瑞丽, 等. 钩藤碱通过抑Smad信号通路磷酸化减轻腹腔粘连发生的作用机制. 药学学报, 2017, 52(2): 229-235.

1. 付海军. 腹外疝外科应注意的几个问题. 亚太传统医药, 2011, 7(8): 110-111.
2. Kingsnorth A, LeBlanc K. Hernias: inguinal and incisional. Lancet, 2003, 362(9395): 1561-1571.
3. Kamel RM. Prevention of postoperative peritoneal adhesions. Eur J Obstet Gynecol Reprod Biol, 2010, 150(2): 111-118.
4. Boland GM, Weigel RJ. Formation and prevention of postoperative abdominal adhesions. J Surg Res, 2006, 132(1): 3-12.
5. Sahbaz A, Aynioglu O, Isik H, et al. Bromelain: a natural proteolytic for intra-abdominal adhesion prevention. Int J Surg, 2015, 14: 7-11.
6. Coleman MG, McLain AD, Moran BJ. Impact of previous surgery on time taken for incision and division of adhesions during laparotomy. Dis Colon Rectum, 2000, 43(9): 1297-1299.
7. Hosseini A, Akhavan S, Menshaei M, et al. Effects of streptokinase and normal saline on the incidence of intra-abdominal adhesion 1 week and 1 month after laparotomy in rats. Adv Biomed Res, 2018, 7: 16.
8. Bryers JD, Giachelli CM, Ratner BD. Engineering biomaterials to integrate and heal: the biocompatibility paradigm shifts. Biotechnol Bioeng, 2012, 109(8): 1898-1911.
9. Sadava EE, Krpata DM, Gao Y, et al. Wound healing process and mediators: implications for modulations for hernia repair and mesh integration. J Biomed Mater Res Part A, 2014, 102(1): 295-302.
10. Poppas DP, Sung JJ, Magro CM, et al. Hydrogel coated mesh decreases tissue reaction resulting from polypropylene mesh implant: implication in hernia repair. Hernia, 2016, 20(4): 623-632.
11. Scheidback H, Tamme C, Tannapfel A, et al. In vivo studies comparing the biocompatibility of various polypropylene meshes and their handling properties during endoscopic total extraperitoneal (TEP) patchplasty: an experimental study in pigs. Surg Endosc, 2004, 18(2): 211-220.
12. Zhang Z, Zhang T, Li J,, et al. Preparation of poly( L-lactic acid) - modified polypropylene mesh and its antiadhesion in experimental abdominal wall defect repair. J Biome Mater Res B Appl Biomater, 2014, 102(1): 12-21.
13. Laschke MW, Häufel JM, Roller J, et al. Rapamycin, but not cyclosporine A, inhibits vascularization and incorporation of implanted surgical meshes. Transpl Int, 2009, 22(6): 654-662.
14. Shah PR, Kute VB, Patel HV, et al. Therapeutic drug monitoring of sirolimus. Clinical Queries: Nephrology, 2015, 4: 44-49.
15. Dilling DF, Nair A, Gries CJ, et al. Use of sirolimus in patients with lymphangioleiomyomatosis (LAM) on waiting lists for lung transplant (LTX). J Heart Lung Transplant, 2018, 37(4): s457.
16. Lai ZW, Kelly R, Winans T, et al. Sirolimus in patients with clinically active systemic lupus erythematosus resistant to, or intolerant of, conventional medications: a single-arm, open-label, phase 1/2 trial. Lancet, 2018, 391(10126): 1186-1196.
17. 任常, 朱兰. 盆腹腔手术后粘连的分类及评价方法. 中华妇产科杂志, 2012, 47(4): 317-318.
18. Ye XL, Han XY, Wei B, et al. Ventral hernia repair in rat using nanofibrous polylactic acid/polypropylene meshes. Nanomedicine (Lond), 2018, 13(17): 2187-2199.
19. Grant S, Ramshaw B. Progress in synthetic prosthetic mesh for ventral hernia repair//LeBlanc K, Kingsnorth A, Sanders D. Management of abdominal hernias. 5 ed. Springer, Cham, 2018: 173-178.
20. Zhang C, Salick MR, Cordie TM, et al. Incorporation of poly(ethylene glycol) grafted cellulose nanocrystals in poly(lactic acid) electrospun nanocomposite fibers as potential scaffolds for bone tissue engineering. Mater Sci Eng C Mater Biol Appl, 2015, 49: 463-471.
21. Kong CY, Lai LL, Khoo AYY, et al. Inflammatory reaction to fish oil coated polypropylene mesh used for laparoscopic incisional hernia repair: a case report. BMC Surg, 2016, 16: 8.
22. Vermet G, Degoutin S, Chai F, et al. Cyclodextrin modified PLLA parietal reinforcement implant with prolonged antibacterial activity. Acta Biomater, 2017, 53: 222-232.
23. Bayhan Z, Zeren S, Kocak FE, et al. Antiadhesive and anti-inflammatory effects of pirfenidone in postoperative intra-abdominal adhesion in an experimental rat model. J Surg Res, 2016, 201(2): 348-355.
24. 宋宇, 张慧, 刘瑞丽, 等. 钩藤碱通过抑Smad信号通路磷酸化减轻腹腔粘连发生的作用机制. 药学学报, 2017, 52(2): 229-235.

West China Medical Journal

Preparation and animal experiment of a novel sirolimus drug-coated mesh

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