Thrombus organization and healing in an experimental aneurysm model. Part II. The effect of various types of bioactive bioabsorbable polymeric coils

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Object

Bioabsorbable polymeric material coils are being used in the endovascular treatment of aneurysms to achieve better thrombus organization than is possible using bare platinum coils. We used immunohistochemical and molecular biological analysis techniques in experimental aneurysms implanted with three different bioabsorbable polymer coils and platinum coils.

Methods

The degradation kinetics of nine polymer candidates for further analysis were first analyzed in vitro, and three materials with different degradation rates were selected. Seventy-four aneurysms were created in 37 swine using the venous pouch technique. The aneurysms were surgically implanted with one of the materials as follows (time points = 3, 7, and 14 days): Group 1, Guglielmi detachable coils (platinum); Group 2, Polysorb (90:10 polyglycolic acid [PGA]/polylactic acid); Group 3, Maxon (PGA/trimethylene carbonate); and Group 4, poly-l-lactic acid. Histological, immunohistochemical, and cDNA microarray analyses were performed on tissue specimens.

Results

Groups 1 and 4 showed minimal inflammatory response adjacent to the coil mass. In Group 2, Polysorb elicited a unique, firm granulation tissue that accelerated intraaneurysmal thrombus organization. In Group 3 intermediate inflammatory reactions were seen. Microarray analysis with Expression Analysis Sytematic Explorer software showed functional-cluster-gene activation to be increased at Day 7, preceding the histologic manifestation of polymer-induced granulation tissue at Day 14. A profile of expression changes in cytokine-related and extracellular membrane–related genes was compiled.

Conclusions

Degradation speed was not the only factor determining the strength of the biological response. Polysorb induced an early, unique granulation tissue that conferred greater mechanical strength to the intraaneurysmal coil–thrombus complex. Enhancing the formation of this polymer-induced granulation tissue may provide a new direction for improving long-term anatomical outcomes in cases involving aneurysms embolized with detachable coils.

Abbreviations used in this paper:BPM = bioabsorbable polymeric material; EASE = Expression Analysis Systematic Explorer; ECM = extracellular matrix; GDC = Guglielmi detachable coil; GPC = gel permeation chromatography; IGF = insulin-like growth factor; IGFBP = IGF-binding protein; MMP = matrix metalloproteinase; PGA = polyglycolic acid; PLA = polylactic acid; PLLA = poly-l-lactic acid; TMC = trimethylene carbonate; UCLA = University of California Los Angeles.

Article Information

Address reprint requests to: Ichiro Yuki, M.D., Division of Interventional Neuroradiology, UCLA Medical Center and David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, California 90095–1721. email: iyuki@mednet.ucla.edu.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    Bar graph showing the results of in vitro study of rate of loss of molecular weight over 2 weeks in the original nine candidate polymers. Maxon demonstrated the fastest rate of degradation, Polysorb an intermediate rate, and PLLA the slowest rate. PCL = ε-caprolactone; PDO = poly-p-dioxanone.

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    Representative photographs of gross specimens of aneurysms treated with Polysorb (A and B), PLLA (C), and Maxon (D). Homogeneous immature thrombus was seen at postoperative Day 7 in all specimens (A). White rubbery tissue (organized thrombus) developed from the wall and filled the intraluminal space in a centripetal fashion (in every Day 14 sample). Note that the Polysorb-implanted sample showed the most intense thrombus organization (B).

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    Representative photomicrographs of stained sections demonstrating the degree of inflammation and cellular density after Polysorb (A), Maxon (B), PLLA (C), and GDC (D) coil implantation. Masson trichrome, original magnification × 100.

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    A: Photograph of an aneurysm harvested at Day 14 from the Polysorb group. B: Photomicrograph of a section from the same aneurysm showing polymer-induced granulation tissue. Note the presence of collagen deposition around the coil mass but not within the interstices. Sirius red, original magnification × 40.

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    Photomicrographs showing the polymer-induced granulation tissue that was seen in Polysorb-treated aneurysms at Day 14. A: Masson trichrome staining shows the noncollagen tissue adjacent to coil materials (arrow). B: Staining with H & E indicates foreign-body giant cells around the coil material (arrowhead). C: Positive expressions of immunoreactive cells around the coil material (red arrow).

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    Photomicrographs showing fluorescence-enhanced Sirius red staining demonstrating collagen fiber alignment in GDC-treated (A) and Polysorb-treated (B) aneurysms. Original magnification × 200.

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    Graph illustrating the results of quantitative immunohistochemical analysis of macrophage density. Note persistent macrophage enrichment in Polysorb-treated aneurysms at Day 14. MAX = Maxon; POLY = Polysorb.

  • View in gallery

    Graph illustrating the results of EASE functional clustering. Note that specific genes may be related to multiple functional classes.

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