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Biodegradable and thermosensitive micelles inhibit ischemia-induced postoperative peritoneal adhesion.

Wu Q, Li L, Wang N, Gao X, Wang B, Liu X, Qian Z, Wei Y, Gong C - Int J Nanomedicine (2014)

Bottom Line: We found that the synthesized PCL-PEG-PCL copolymer could self-assemble in an aqueous solution to form micelles with a mean size of 40.1 ± 2.7 nm at 10°C, and the self-assembled micelles could instantly turn into a nonflowing gel at body temperature.On Day 7 after micelle treatment, a layer of neo-mesothelial cells emerged on the injured tissues, which confirmed the antiadhesion effect of the micelles.The thermosensitive micelles had no significant side effects in the in vivo experiments.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China.

ABSTRACT
Ischemia-induced adhesion is very common after surgery, and leads to severe abdominal adhesions. Unfortunately, many existing barrier agents used for adhesion prevention have only limited success. The objective of this study is to evaluate the efficacy of biodegradable and thermosensitive poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL) micelles for the prevention of postoperative ischemia-induced adhesion. We found that the synthesized PCL-PEG-PCL copolymer could self-assemble in an aqueous solution to form micelles with a mean size of 40.1 ± 2.7 nm at 10°C, and the self-assembled micelles could instantly turn into a nonflowing gel at body temperature. In vitro cytotoxicity tests suggested that the copolymer showed little toxicity on NIH-3T3 cells even at amounts up to 1,000 μg/mL. In the in vivo test, the postsurgical ischemic-induced peritoneal adhesion model was established and then treated with the biodegradable and thermosensitive micelles. In the control group (n=12), all animals developed adhesions (mean score, 3.58 ± 0.51), whereas three rats in the micelles-treated group (n=12) did not develop any adhesions (mean score, 0.67 ± 0.78; P<0.001, Mann-Whitney U-test). Both hematoxylin and eosin and Masson trichrome staining of the ischemic tissues indicated that the micelles demonstrated excellent therapeutic effects on ischemia-induced adhesion. On Day 7 after micelle treatment, a layer of neo-mesothelial cells emerged on the injured tissues, which confirmed the antiadhesion effect of the micelles. The thermosensitive micelles had no significant side effects in the in vivo experiments. These results suggested that biodegradable and thermosensitive PCL-PEG-PCL micelles could serve as a potential barrier agent to reduce the severity of and even prevent the formation of ischemia-induced adhesions.

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Histopathological analyses of tissues from control group and micelles-treated group.Notes: (A) Adhesion tissues from control group stained with H&E (100×). (B) Adhesion tissues from control group stained with Masson (100×). (C) Tissues from micelles-treated group stained with H&E (100×). (D) Tissues from micelles-treated group stained with Masson (100×). (E) The appearance of neo-mesothelial cells in tissues stained with H&E on Day 7 after micelles treatment (400×). (F) The appearance of neo-mesothelial cells in tissues stained with Masson on Day 7 after micelles treatment (400×). Black arrows in each slide showed the position of adhesion or mesothelial cells in each figure.Abbreviations: H&E, hematoxylin and eosin; Me, mesothelial cells; SK, abdominal wall skeletal muscle; SS, silk suture.
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f6-ijn-9-727: Histopathological analyses of tissues from control group and micelles-treated group.Notes: (A) Adhesion tissues from control group stained with H&E (100×). (B) Adhesion tissues from control group stained with Masson (100×). (C) Tissues from micelles-treated group stained with H&E (100×). (D) Tissues from micelles-treated group stained with Masson (100×). (E) The appearance of neo-mesothelial cells in tissues stained with H&E on Day 7 after micelles treatment (400×). (F) The appearance of neo-mesothelial cells in tissues stained with Masson on Day 7 after micelles treatment (400×). Black arrows in each slide showed the position of adhesion or mesothelial cells in each figure.Abbreviations: H&E, hematoxylin and eosin; Me, mesothelial cells; SK, abdominal wall skeletal muscle; SS, silk suture.

Mentions: Tissue samples from ischemic buttons in each group were collected and stained with H&E and Masson trichrome staining. As shown in Figure 6A and 6B, in the control group, ischemic buttons were formed with silk sutures buried in the fibrous tissues. Connective tissues of the omentum were adhered to the surface and peripheral area of the ischemic button. Dense adhesions were observed between the ischemic button and connective tissues, and no mesothelial cells were observed on the surface of the ischemic button.


Biodegradable and thermosensitive micelles inhibit ischemia-induced postoperative peritoneal adhesion.

Wu Q, Li L, Wang N, Gao X, Wang B, Liu X, Qian Z, Wei Y, Gong C - Int J Nanomedicine (2014)

Histopathological analyses of tissues from control group and micelles-treated group.Notes: (A) Adhesion tissues from control group stained with H&E (100×). (B) Adhesion tissues from control group stained with Masson (100×). (C) Tissues from micelles-treated group stained with H&E (100×). (D) Tissues from micelles-treated group stained with Masson (100×). (E) The appearance of neo-mesothelial cells in tissues stained with H&E on Day 7 after micelles treatment (400×). (F) The appearance of neo-mesothelial cells in tissues stained with Masson on Day 7 after micelles treatment (400×). Black arrows in each slide showed the position of adhesion or mesothelial cells in each figure.Abbreviations: H&E, hematoxylin and eosin; Me, mesothelial cells; SK, abdominal wall skeletal muscle; SS, silk suture.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3921091&req=5

f6-ijn-9-727: Histopathological analyses of tissues from control group and micelles-treated group.Notes: (A) Adhesion tissues from control group stained with H&E (100×). (B) Adhesion tissues from control group stained with Masson (100×). (C) Tissues from micelles-treated group stained with H&E (100×). (D) Tissues from micelles-treated group stained with Masson (100×). (E) The appearance of neo-mesothelial cells in tissues stained with H&E on Day 7 after micelles treatment (400×). (F) The appearance of neo-mesothelial cells in tissues stained with Masson on Day 7 after micelles treatment (400×). Black arrows in each slide showed the position of adhesion or mesothelial cells in each figure.Abbreviations: H&E, hematoxylin and eosin; Me, mesothelial cells; SK, abdominal wall skeletal muscle; SS, silk suture.
Mentions: Tissue samples from ischemic buttons in each group were collected and stained with H&E and Masson trichrome staining. As shown in Figure 6A and 6B, in the control group, ischemic buttons were formed with silk sutures buried in the fibrous tissues. Connective tissues of the omentum were adhered to the surface and peripheral area of the ischemic button. Dense adhesions were observed between the ischemic button and connective tissues, and no mesothelial cells were observed on the surface of the ischemic button.

Bottom Line: We found that the synthesized PCL-PEG-PCL copolymer could self-assemble in an aqueous solution to form micelles with a mean size of 40.1 ± 2.7 nm at 10°C, and the self-assembled micelles could instantly turn into a nonflowing gel at body temperature.On Day 7 after micelle treatment, a layer of neo-mesothelial cells emerged on the injured tissues, which confirmed the antiadhesion effect of the micelles.The thermosensitive micelles had no significant side effects in the in vivo experiments.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China.

ABSTRACT
Ischemia-induced adhesion is very common after surgery, and leads to severe abdominal adhesions. Unfortunately, many existing barrier agents used for adhesion prevention have only limited success. The objective of this study is to evaluate the efficacy of biodegradable and thermosensitive poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL) micelles for the prevention of postoperative ischemia-induced adhesion. We found that the synthesized PCL-PEG-PCL copolymer could self-assemble in an aqueous solution to form micelles with a mean size of 40.1 ± 2.7 nm at 10°C, and the self-assembled micelles could instantly turn into a nonflowing gel at body temperature. In vitro cytotoxicity tests suggested that the copolymer showed little toxicity on NIH-3T3 cells even at amounts up to 1,000 μg/mL. In the in vivo test, the postsurgical ischemic-induced peritoneal adhesion model was established and then treated with the biodegradable and thermosensitive micelles. In the control group (n=12), all animals developed adhesions (mean score, 3.58 ± 0.51), whereas three rats in the micelles-treated group (n=12) did not develop any adhesions (mean score, 0.67 ± 0.78; P<0.001, Mann-Whitney U-test). Both hematoxylin and eosin and Masson trichrome staining of the ischemic tissues indicated that the micelles demonstrated excellent therapeutic effects on ischemia-induced adhesion. On Day 7 after micelle treatment, a layer of neo-mesothelial cells emerged on the injured tissues, which confirmed the antiadhesion effect of the micelles. The thermosensitive micelles had no significant side effects in the in vivo experiments. These results suggested that biodegradable and thermosensitive PCL-PEG-PCL micelles could serve as a potential barrier agent to reduce the severity of and even prevent the formation of ischemia-induced adhesions.

Show MeSH
Related in: MedlinePlus