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

Ichiro Yuki M.D., Daniel Lee M.D., Yuichi Murayama M.D., Alexander Chiang B.S., Harry V. Vinters M.D., Ichiro Nishimura D.M.Sc., D.M.D., Chiachien J. Wang Ph.D., Akira Ishii M.D., Benjamin M. Wu D.D.S., Ph.D. and Fernando Viñuela M.D.
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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.

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Contributor Notes

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.
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