Thrombus organization and healing in an experimental aneurysm model. Part II. The effect of various types of bioactive bioabsorbable polymeric coils.
OBJECTIVE
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 coilthrombus 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.
Yuki
Ichiro
I
Division of Interventional Neuroradiology, Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, California 90095-1721, USA. iyuki@mednet.ucla.edu
Lee
Daniel
D
Murayama
Yuichi
Y
Chiang
Alexander
A
Vinters
Harry V
HV
Nismmura
Ichiro
I
Wang
Chiachien J
CJ
Ishii
Akira
A
Wu
Benjamin M
BM
Viñuela
Fernando
F
D020341:Absorbable Implants; D000818:Animals; D002874:Chromosome Mapping; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D004621:Embolization, Therapeutic / Q000295:instrumentation; D004867:Equipment Design; D005260:Female; D015870:Gene Expression / Q000235:genetics; D006097:Granulation Tissue / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D055436:Growth Differentiation Factor 15; D007150:Immunohistochemistry; D002532:Intracranial Aneurysm / Q000235:genetics / Q000473:pathology* / Q000628:therapy*; D008297:Male; D046228:Microarray Analysis; D020411:Oligonucleotide Array Sequence Analysis; D011108:Polymers / Q000494:pharmacology / Q000627:therapeutic use*; D012313:RNA / Q000032:analysis; D012984:Software; D013552:Swine; D014945:Wound Healing
D016207:Cytokines; D055436:Growth Differentiation Factor 15; D011108:Polymers; D012313:RNA