Study on the prevention of postoperative intraperitoneal adhesion of rat with PLGA/PEG electrospun polymer membrane_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

CHEN Zaomei ^1,2 , ZHAO Yue ^1,2 , HE Ting ³ , CHEN Kejun ^1,2 , JIANG Li ² , ZHANG Junhui ³ , WAN Huayin ³ ,  LI Rubing ^1,2

1. Pharmaceutical college of Guangdong Pharmaceutical University, Guangzhou Guangdong, 510006, P.R.China;
2. Department of Pharmacy, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou Guangdong, 510010, P.R.China;
3. Guangzhou Electrospinning Biological Technology Co.Ltd., Guangzhou Guangdong, 510604, P.R.China;

Corresponding?author：

LI Rubing, Email: lrb90927@126.com

Keywords：

Intraperitoneal adhesion; electrospinning technology; anti-adhesion membrane; poly-L-lactic/glycolic acid; polyethylene glycol; biodegradability; rat

DOI：

10.7507/1002-1892.201703083

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ObjectiveAdopting poly-L-lactic/glycolic acid (PLGA) and polyethylene glycol (PEG) as the material to fabricate PLGA/PEG electrospun polymer membrane by electrospinning technology. And to study its preventive effect on postoperative intraperitoneal adhesion of rat.MethodsPLGA and PEG were mixed at the ratio of 19∶1(M/M), then dissolved in organic solvent. The PLGA/PEG electrospun polymer membrane was prepared by electrospinning technology, and then the gross observation and scanning electron microscope observation were taken. Fifty-four Sprague Dawley rats (weighing, 180-200 g), were randomly divided into 3 groups. The rats in control group (n=6) were left intact. The rats in model group (n=24) and PLGA/PEG group (n=24) were treated with the method of mechanical injury of the cecal serosa in order to establish the intraperitoneal adhesion models; then the PLGA/PEG electrospun polymer membrane was used to cover the wound in PLGA/PEG group, but was not in the model group. The intraperitoneal adhesion in PLGA/PEG group and model group were observed at 3 days, 1 week, 2 weeks, and 8 weeks after operation, and the adhesion degree was assessed according to the self-generated standard. The degradation of PLGA/PEG electrospun polymer membrane was also observed in PLGA/PEG group. At each time point, the rats were harvested for histological observation. All the above indexes were compared with the control group.ResultsUsing the electrospinning technology, PLGA/PEG electrospun polymer membrane was prepared successfully. PLGA/PEG electrospun polymer membrane was white and opaque, with soft texture. Scanning electron microscopy observation showed that PLGA/PEG electrospun polymer membrane was mainly composed of disorderly staggered fibers, with microporous structure. All rats survived to the end of the experiment. Gross observation showed that PLGA/PEG electrospun polymer membrane gradually degraded after implantation in vivo, and the adhesion degree in PLGA/PEG group was significantly lower than that in model group (P<0.05), but it had not yet reached to the level of the control group (P<0.05). Histological observation showed that the proliferation of cecal fibrous connective tissue was slower in PLGA/PEG group than in model group, and adhesion severity significantly decreased, only with a small amount of inflammatory cell infiltration. Nevertheless, it was not up to the level of the control group.ConclusionPLGA/PEG electrospun polymer membrane can effectively prevent postoperative intraperitoneal adhesion of rat, and has good biodegradability.

Citation： CHEN Zaomei, ZHAO Yue, HE Ting, CHEN Kejun, JIANG Li, ZHANG Junhui, WAN Huayin, LI Rubing. Study on the prevention of postoperative intraperitoneal adhesion of rat with PLGA/PEG electrospun polymer membrane. Chinese Journal of Reparative and Reconstructive Surgery, 2017, 31(8): 999-1005. doi: 10.7507/1002-1892.201703083 Copy

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2.	曾煦欣, 楊西曉, 黃嗣航, 等. 術后粘連防治藥物的藥效學動物模型制作與評價. 中國新藥雜志, 2005, 14(7): 814-817.
3.	蘇媛媛. 婦科腹腔鏡手術不同氣腹壓力的變化對細胞因子的影響. 沈陽: 中國醫科大學, 2010.
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6.	Lauder CI, Garcea G, Strickland A, et al. Abdominal adhesion prevention: still a sticky subject? Dig Surg, 2010, 27(5): 347-358.
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8.	Na SY, Oh SH, Song KS, et al. Hyaluronic acid/mildly crosslinked alginate hydrogel as an injectable tissue adhesion barrier. J Mater Sci Mater Med, 2012, 3(9): 2303-2313.
9.	陽剛. 復合肌腱修復材料-載細胞用防粘連性隔離/支架型 PLGA 膜的體外研制. 長沙: 中南大學, 2010.
10.	甘少磊, 王萬霞. 含鈣離子和透明質酸的復合凝膠術后防粘連材料及其制備方法. 中國, CN101879334A. [2010-06-21].
11.	譚輝. 聚乳酸與羧甲基纖維素鈉復合膜的制備及其性能研究. 廣州: 華南理工大學, 2011.
12.	張誠. 聚乳酸-乙醇酸共聚物的降解性能研究. 北京: 北京服裝學院, 2012.
13.	龐秀炳, 潘永明, 華菲, 等. 聚乳酸/乙醇酸可吸收醫用膜對兔腹腔術后粘連的預防作用研究. 中國醫療器械雜志, 2014, 38(5): 389-392.
14.	Chen CH, Chen SH, Shalumon KT, et al. Prevention of peritendinous adhesions with electrospun polyethylene glycol/polycaprolactone nanofibrous membranes. Colloids Surf B Biointerfaces, 2015, 133: 221-230.
15.	宋具昆, 包崇云, 袁明龍, 等. 可生物降解凝膠膜預防腹腔術后粘連的實驗研究. 四川大學學報(醫學版), 2007, 38(4): 660-662.
16.	Zheng Z, Zhang W, Sun W, et al. Influence of the carboxymethyl chitosan anti-adhesion solution on the TGF-β1 in a postoperative peritoneal adhesion rat. J Mater Sci Mater Med, 2013, 24(11): 2549-2559.
17.	Belluco C, Meggiolaro F, Pressato D, et al. Prevention of postsurgical adhesions with an autocross linked hyaluronan derivative gel. J Surg Res, 2001, 100(2): 217-221.
18.	Phillips RK, Dudley HA. The effect of tetracycline lavage and trauma on visceral and parietal peritoneal ultrastructure and adhesion formation. Br J Surg, 1984, 71(7): 537-539.
19.	陳灶妹, 李茹冰. 可吸收防粘連膜的應用研究與未來展望. 中國組織工程研究, 2017, 21(18): 2920-2926.
20.	徐瑞. 多微孔硅橡膠仿生敷料的制備及其對創面愈合的影響與機制研究. 重慶: 第三軍醫大學, 2016.
21.	辛國華, 曾逃方, 羅旭, 等. 微孔結構對脫細胞真皮基質膠原網架功能重建的影響. 廣東醫學, 2012, 33(3): 310-312.
22.	徐偉力, 朱偉民, 黃江鴻, 等. 軟骨組織工程支架材料研究進展. 國際骨科學雜志, 2014, 35(4): 247-249.
23.	朱燕. 基于大鼠腹膜間皮細胞 TGF-β/Smad 信號途徑研究川芎嗪納米噴霧劑抗實驗性腹腔粘連作用機制. 南京: 南京中醫藥大學, 2015.

1. 馬俊秋. Seprafilm 預防大鼠術后腹腔粘連的實驗研究. 長春: 吉林大學, 2013.
2. 曾煦欣, 楊西曉, 黃嗣航, 等. 術后粘連防治藥物的藥效學動物模型制作與評價. 中國新藥雜志, 2005, 14(7): 814-817.
3. 蘇媛媛. 婦科腹腔鏡手術不同氣腹壓力的變化對細胞因子的影響. 沈陽: 中國醫科大學, 2010.
4. 程學遠. 術后腸粘連的發生機制及研究進展. 北方藥學, 2014, 11(12): 101-102.
5. Brochhausen C, Schmitt VH, Rajab TK, et al. Intraperitoneal adhesions-an ongoing challenge between biomedical engineering and the life sciences. Biomed Mater Res A, 2011, 98(1): 143-156.
6. Lauder CI, Garcea G, Strickland A, et al. Abdominal adhesion prevention: still a sticky subject? Dig Surg, 2010, 27(5): 347-358.
7. 倪健. 溫敏可注射性水凝膠抗兔術后腹腔粘連的實驗研究. 上海: 復旦大學, 2011.
8. Na SY, Oh SH, Song KS, et al. Hyaluronic acid/mildly crosslinked alginate hydrogel as an injectable tissue adhesion barrier. J Mater Sci Mater Med, 2012, 3(9): 2303-2313.
9. 陽剛. 復合肌腱修復材料-載細胞用防粘連性隔離/支架型 PLGA 膜的體外研制. 長沙: 中南大學, 2010.
10. 甘少磊, 王萬霞. 含鈣離子和透明質酸的復合凝膠術后防粘連材料及其制備方法. 中國, CN101879334A. [2010-06-21].
11. 譚輝. 聚乳酸與羧甲基纖維素鈉復合膜的制備及其性能研究. 廣州: 華南理工大學, 2011.
12. 張誠. 聚乳酸-乙醇酸共聚物的降解性能研究. 北京: 北京服裝學院, 2012.
13. 龐秀炳, 潘永明, 華菲, 等. 聚乳酸/乙醇酸可吸收醫用膜對兔腹腔術后粘連的預防作用研究. 中國醫療器械雜志, 2014, 38(5): 389-392.
14. Chen CH, Chen SH, Shalumon KT, et al. Prevention of peritendinous adhesions with electrospun polyethylene glycol/polycaprolactone nanofibrous membranes. Colloids Surf B Biointerfaces, 2015, 133: 221-230.
15. 宋具昆, 包崇云, 袁明龍, 等. 可生物降解凝膠膜預防腹腔術后粘連的實驗研究. 四川大學學報(醫學版), 2007, 38(4): 660-662.
16. Zheng Z, Zhang W, Sun W, et al. Influence of the carboxymethyl chitosan anti-adhesion solution on the TGF-β1 in a postoperative peritoneal adhesion rat. J Mater Sci Mater Med, 2013, 24(11): 2549-2559.
17. Belluco C, Meggiolaro F, Pressato D, et al. Prevention of postsurgical adhesions with an autocross linked hyaluronan derivative gel. J Surg Res, 2001, 100(2): 217-221.
18. Phillips RK, Dudley HA. The effect of tetracycline lavage and trauma on visceral and parietal peritoneal ultrastructure and adhesion formation. Br J Surg, 1984, 71(7): 537-539.
19. 陳灶妹, 李茹冰. 可吸收防粘連膜的應用研究與未來展望. 中國組織工程研究, 2017, 21(18): 2920-2926.
20. 徐瑞. 多微孔硅橡膠仿生敷料的制備及其對創面愈合的影響與機制研究. 重慶: 第三軍醫大學, 2016.
21. 辛國華, 曾逃方, 羅旭, 等. 微孔結構對脫細胞真皮基質膠原網架功能重建的影響. 廣東醫學, 2012, 33(3): 310-312.
22. 徐偉力, 朱偉民, 黃江鴻, 等. 軟骨組織工程支架材料研究進展. 國際骨科學雜志, 2014, 35(4): 247-249.
23. 朱燕. 基于大鼠腹膜間皮細胞 TGF-β/Smad 信號途徑研究川芎嗪納米噴霧劑抗實驗性腹腔粘連作用機制. 南京: 南京中醫藥大學, 2015.

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