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

Ichiro Yuki null

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 M.D.
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Daniel Lee null

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 M.D.
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Yuichi Murayama null

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 M.D.
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Alexander Chiang null

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 B.S.
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Harry V. Vinters null
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 M.D.
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Ichiro Nishimura null

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 D.M.Sc., D.M.D.
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Chiachien J. Wang null

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Akira Ishii null

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Benjamin M. Wu null

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 D.D.S., Ph.D.
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Fernando Viñuela null

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 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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  • 1

    Abrahams JM, , Forman MS, , Grady MS, & Diamond SL: Delivery of human vascular endothelial growth factor with platinum coils enhances wall thickening and coil impregnation in a rat aneurysm model. AJNR Am J Neuroradiol 22:14101417, 2001

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Athanasiou KA, , Agrawal CM, , Barber FA, & Burkhart SS: Orthopaedic applications for PLA-PGA biodegradable polymers. Arthroscopy 14:726737, 1998

  • 3

    Bavinzski G, , Talazoglu V, , Killer M, , Richling B, , Gruber A, & Gross CE, et al.: Gross and microscopic histopathological findings in aneurysms of the human brain treated with Guglielmi detachable coils. J Neurosurg 91:284293, 1999

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Bergsma JE, , de Bruijn WC, , Rozema FR, , Bos RR, & Boering G: Late degradation tissue response to poly(L-lactide) bone plates and screws. Biomaterials 16:2531, 1995

  • 5

    Bornstein P, , Agah A, & Kyriakides TR: The role of thrombospondins 1 and 2 in the regulation of cell-matrix interactions, collagen fibril formation, and the response to injury. Int J Biochem Cell Biol 36:11151125, 2004

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Cahill DW, , Martin GJ Jr, , Hajjar MV, , Sonstein W, , Graham LB, & Engelman RW: Suitability of bioresorbable cages for anterior cervical fusion. J Neurosurg 98:2 Suppl 195201, 2003

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Chu CC, , von Fraunhofer JA, & Greisler HP: Wound Closure Biomaterials and Devices Boca Raton, FL, CRC Press, 1996

  • 8

    Cloft HJ, , Altes TA, , Marx WF, , Raible RJ, , Hudson SB, & Helm GA, et al.: Endovascular creation of an in vivo bifurcation aneurysm model in rabbits. Radiology 213:223228, 1999

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Dahab GM, , Kheriza MM, , El-Beltagi HM, , Fouda AM, & El-Din OA: Digital quantification of fibrosis in liver biopsy sections: description of a new method by Photoshop software. J Gastroenterol Hepatol 19:7885, 2004

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Dai D, , Ding YH, , Danielson MA, , Kadirvel R, , Lewis DA, & Cloft HJ, et al.: Modified histologic technique for processing metallic coil-bearing tissue. AJNR Am J Neuroradiol 26:19321936, 2005

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    de Gast AN, , Altes TA, , Marx WF, , Do HM, , Helm GA, & Kallmes DF: Transforming growth factor beta-coated platinum coils for endovascular treatment of aneurysms: an animal study. Neurosurgery 49:690696, 2001

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Ehrlich HP: The role of connective tissue matrix in wound healing. Prog Clin Biol Res 266:243258, 1988

  • 13

    Gillitzer R, & Goebeler M: Chemokines in cutaneous wound healing. J Leukoc Biol 69:513521, 2001

  • 14

    Hoh BL, , Topcuoglu MA, , Singhal AB, , Pryor JC, , Rabinov JD, & Rordorf GA, et al.: Effect of clipping, craniotomy, or intravascular coiling on cerebral vasospasm and patient outcome after aneurysmal subarachnoid hemorrhage. Neurosurgery 55:779789, 2004

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Hosack DA, , Dennis G Jr, , Sherman BT, , Lane HC, & Lempicki RA: Identifying biological themes within lists of genes with EASE. Genome Biol 4:R70, 2003

  • 16

    Ji W, , Zhou W, , Gregg K, , Lindpaintner K, & Davis S: A method for gene expression analysis by oligonucleotide arrays from minute biological materials. Anal Biochem 331:329339, 2004

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Ji W, , Zhou W, , Gregg K, , Yu N, & Davis S: A method for cross-species gene expression analysis with high-density oligonucleotide arrays. Nucleic Acids Res 32:E93, 2004

  • 18

    Kallmes DF, , Helm GA, , Hudson SB, , Altes TA, , Do HM, & Mandell JW, et al.: Histologic evaluation of platinum coil embolization in an aneurysm model in rabbits. Radiology 213:217222, 1999

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Lai LP, , Lin JL, , Lin CS, , Yeh HM, , Tsay YG, & Lee CF, et al.: Functional genomic study on atrial fibrillation using cDNA microarray and two-dimensional protein electrophoresis techniques and identification of the myosin regulatory light chain isoform reprogramming in atrial fibrillation. J Cardiovasc Electrophysiol 15:214223, 2004

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Lee D, , Yuki I, , Murayama Y, , Chiang A, , Nishimura I, & Vinters HV, et al.: Thrombus organization and healing in the swine experimental aneurysm model. Part I A histological and molecular analysis. J Neurosurg 107:94108, 2007

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Medhora M, , Bousamra M II, , Zhu D, , Somberg L, & Jacobs ER: Upregulation of collagens detected by gene array in a model of flow-induced pulmonary vascular remodeling. Am J Physiol Heart Circ Physiol 282:H414H422, 2002

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Miller RA, , Brady JM, & Cutright DE: Degradation rates of oral resorbable implants (polylactates and polyglycolates): rate modification with changes in PLA/PGA copolymer ratios. J Biomed Mater Res 11:711719, 1977

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Mizoi K, , Yoshimoto T, , Takahashi A, & Nagamine Y: A pitfall in the surgery of a recurrent aneurysm after coil embolization and its histological observation: technical case report. Neurosurgery 39:165169, 1996

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Moldovan NI, & Asahara T: Role of blood mononuclear cells in recanalization and vascularization of thrombi: past, present, and future. Trends Cardiovasc Med 13:265269, 2003

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Molyneux A, , Kerr R, , Stratton I, , Sandercock P, , Clarke M, & Shrimpton J, et al.: International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised trial. Lancet 360:12671274, 2002

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Molyneux AJ, , Kerr RS, , Yu LM, , Clarke M, , Sneade M, & Yarnold JA, et al.: International subarachnoid aneurysm trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups, and aneurysm occlusion. Lancet 366:809817, 2005

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Moody DE, , Zou Z, & McIntyre L: Cross-species hybridization of pig RNA to human nylon microarrays. BMC Genomics 3:27, 2002

  • 28

    Murayama Y, , Nien YL, , Duckwiler G, , Gobin YP, , Jahan R, & Frazee J, et al.: Guglielmi detachable coil embolization of cerebral aneurysms: 11 years' experience. J Neurosurg 98:959966, 2003

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29

    Murayama Y, , Tateshima S, , Gonzalez NR, & Viñuela F: Matrix and bioabsorbable polymeric coils accelerate healing of intracranial aneurysms: long-term experimental study. Stroke 34:20312037, 2003

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    Murayama Y, , Viñuela F, , Ishii A, , Nien Y, , Yuki I, & Duckwiler G, et al.: Initial clinical experience of matrix detachable coils for the treatment of intracranial aneurysms. J Neurosurg 105:192199, 2006

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31

    Murayama Y, , Viñuela F, , Suzuki Y, , Do HM, , Massoud TF, & Guglielmi G, et al.: Ion implantation and protein coating of detachable coils for endovascular treatment of cerebral aneurysms: concepts and preliminary results in swine models. Neurosurgery 40:12331244, 1997

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32

    Murayama Y, , Viñuela F, , Tateshima S, , Gonzalez NR, , Song JK, & Mahdavieh H, et al.: Cellular responses of bioabsorbable polymeric material and Guglielmi detachable coil in experimental aneurysms. Stroke 33:11201128, 2002

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33

    Ohyama T, , Nishide T, , Iwata H, , Sato H, , Toda M, & Taki W: Vascular endothelial growth factor immobilized on platinum microcoils for the treatment of intracranial aneurysms: experimental rat model study. Neurol Med Chir (Tokyo) 44:279287, 2004

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34

    Ohyama T, , Nishide T, , Iwata H, , Sato H, , Toda M, & Toma N, et al.: Immobilization of basic fibroblast growth factor on a platinum microcoil to enhance tissue organization in intracranial aneurysms. J Neurosurg 102:109115, 2005

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35

    Raymond J, , Metcalfe A, , Desfaits AC, , Ribourtout E, , Salazkin I, & Gilmartin K, et al.: Alginate for endovascular treatment of aneurysms and local growth factor delivery. AJNR Am J Neuroradiol 24:12141221, 2003

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36

    Raymond J, , Venne D, , Allas S, , Roy D, , Oliva VL, & Denbow N, et al.: Healing mechanisms in experimental aneurysms. I Vascular smooth muscle cells and neointima formation. J Neuroradiol 26:720, 1999

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37

    Robert P, , Mauduit J, , Frank RM, & Vert M: Biocompatibility and resorbability of a polylactic acid membrane for periodontal guided tissue regeneration. Biomaterials 14:353358, 1993

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38

    Ross R, & Benditt EP: Wound healing and collagen formation. I Sequential changes in components of guinea pig skin wounds observed in the electron microscope. J Biophys Biochem Cytol 11:677700, 1961

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39

    Sadamasa N, , Nozaki K, & Hashimoto N: Disruption of gene for inducible nitric oxide synthase reduces progression of cerebral aneurysms. Stroke 34:29802984, 2003

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 40

    Wenstrup RJ, , Florer JB, , Brunskill EW, , Bell SM, , Chervoneva I, & Birk DE: Type V collagen controls the initiation of collagen fibril assembly. J Biol Chem 279:5333153337, 2004

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 41

    Wiebers DO, , Whisnant JP, , Huston J III, , Meissner I, , Brown RD Jr, & Piepgras DG, et al.: Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet 362:103110, 2003

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

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