Controlled release of osteopontin and interleukin-10 from modified endovascular coil promote cerebral aneurysm healing

Published:November 20, 2015DOI:


      • Modify the endovascular coil to lower the recurrence rate
      • Modification with osteopontin, IL-10 or matrix metallopeptidase 9 has been tested.
      • Osteopontin and IL-10 coated coils show significant improvement in tissue ingrowth while MMP-9 coated coils failed to.


      Cerebral aneurysm is a bulging of the artery inside the brain that results from a weakened or thin area of the artery wall. Ruptured cerebral aneurysm could lead to serious brain damage or even death, thus the proper treatment is essential. Compared with the conventional microsurgical clipping approach, the endovascular coiling treatment has many advantages, however, with a major disadvantage of high recurrence rate. One way to lower the recurrence rate, which has been tried since one decade ago, is to modify the coil to be bioactive and releasing biological molecules to stimulate tissue ingrowth and aneurysm healing. We have identified three candidates including osteopontin (OPN), IL-10 and matrix metallopeptidase 9 (MMP-9) from previous studies and generated platinum coils coated with these proteins in the carrier of poly-DL-lactic glycolic acid (PLGA). We were interested to know whether coils coated with OPN, IL-10 and MMP-9 were able to promote aneurysm healing and we have tested it in the rat carotid aneurysm model. We found that OPN and IL-10 coated coils had shown significant improvement in tissue ingrowth while MMP-9 coated coils failed to enhance tissue ingrowth compared with the control group. Our studies suggested the possible application of OPN and IL-10 coated coils in aneurysm treatment to overcome the recurrence.


      MMP-9 (matrix metallopeptidase 9), PLGA (poly-DL-lactic glycolic acid), OPN (osteopontin)


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of the Neurological Sciences
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Rinkel G.J.
        Natural history, epidemiology and screening of unruptured intracranial aneurysms.
        Rev. Neurol. (Paris). 2008; 164: 781-786
        • Vlak M.H.
        • Algra A.
        • Brandenburg R.
        • Rinkel G.J.
        Prevalence of unruptured intracranial aneurysms, with emphasis on sex, age, comorbidity, country, and time period: a systematic review and meta-analysis.
        Lancet Neurol. 2011; 10: 626-636
        • Liu A.
        • Huang J.
        Treatment of intracranial aneurysms: clipping versus coiling.
        Current Cardiology Reports. 2015; 17: 628
        • Pierot L.
        • Wakhloo A.K.
        Endovascular treatment of intracranial aneurysms: current status.
        Stroke. 2013; 44: 2046-2054
        • Campi A.
        • Ramzi N.
        • Molyneux A.J.
        • Summers P.E.
        • Kerr R.S.
        • Sneade M.
        • et al.
        Retreatment of ruptured cerebral aneurysms in patients randomized by coiling or clipping in the International Subarachnoid Aneurysm Trial (ISAT).
        Stroke. 2007; 38: 1538-1544
        • Crobeddu E.
        • Lanzino G.
        • Kallmes D.F.
        • Cloft H.J.
        Review of 2 decades of aneurysm-recurrence literature, part 2: managing recurrence after endovascular coiling.
        AJNR Am J Neuroradiol. 2013; 34: 481-485
        • Chalouhi N.
        • Hoh B.L.
        • Hasan D.
        Review of cerebral aneurysm formation, growth, and rupture.
        Stroke. 2013; 44: 3613-3622
        • Chalouhi N.
        • Ali M.S.
        • Jabbour P.M.
        • Tjoumakaris S.I.
        • Gonzalez L.F.
        • Rosenwasser R.H.
        • et al.
        Biology of intracranial aneurysms: role of inflammation.
        J. Cereb. Blood Flow Metab. 2012; 32: 1659-1676
        • Hoh B.L.
        • Hosaka K.
        • Downes D.P.
        • Nowicki K.W.
        • Fernandez C.E.
        • Batich C.D.
        • et al.
        Monocyte chemotactic protein-1 promotes inflammatory vascular repair of murine carotid aneurysms via a macrophage inflammatory protein-1alpha and macrophage inflammatory protein-2-dependent pathway.
        Circulation. 2011; 124: 2243-2252
        • Giachelli C.M.
        • Liaw L.
        • Murry C.E.
        • Schwartz S.M.
        • Almeida M.
        Osteopontin expression in cardiovascular diseases.
        Ann. N. Y. Acad. Sci. 1995; 760: 109-126
        • Vucevic D.
        • Maravic-Stojkovic V.
        • Vasilijic S.
        • Borovic-Labudovic M.
        • Majstorovic I.
        • Radak D.
        • et al.
        Inverse production of IL-6 and IL-10 by abdominal aortic aneurysm explant tissues in culture.
        Cardiovasc. Pathol. 2012; 21: 482-489
        • Kadirvel R.
        • Ding Y.H.
        • Dai D.
        • Lewis D.A.
        • Kallmes D.F.
        Differential gene expression in well-healed and poorly healed experimental aneurysms after coil treatment.
        Radiology. 2010; 257: 418-426
        • Stoscheck C.
        Quantitation of protein.
        Methods Enzymol. 1990; 182: 50-69
        • Abrahams J.M.
        • Forman M.S.
        • Grady M.S.
        • Diamond S.L.
        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. 2001; 22: 1410-1417
        • Knap D.
        • Gruszczynska K.
        • Partyka R.
        • Ptak D.
        • Korzekwa M.
        • Zbroszczyk M.
        • et al.
        Results of endovascular treatment of aneurysms depending on their size, volume and coil packing density.
        Neurol. Neurochir. Pol. 2013; 47: 467-475
        • Leng B.
        • Zheng Y.
        • Ren J.
        • Xu Q.
        • Tian Y.
        • Xu F.
        Endovascular treatment of intracranial aneurysms with detachable coils: correlation between aneurysm volume, packing, and angiographic recurrence.
        J. Neurointerv. Surg. 2014; 6: 595-599
        • Slob M.J.S.M.
        • van Rooij W.J.
        The relation between packing and reopening in coiled intracranial aneurysms: a prospective study.
        Neuroradiology. 2005; 47: 942-945
        • vRW S.M.
        • Slob M.J.
        • et al.
        Relation between aneurysm volume, packing, and compaction in 145 cerebral aneurysms treated with coils.
        Radiology. 2004; 2004: 653-658
        • Brinjikji W.
        • Kallmes D.F.
        • Kadirvel R.
        Mechanisms of healing in coiled intracranial aneurysms: a review of the literature.
        AJNR Am J Neuroradiol. 2015; 36: 1216-1222
        • Kallmes D.F.
        • Fujiwara N.H.
        New expandable hydrogel-platinum coil hybrid device for aneurysm embolization.
        AJNR Am J Neuroradiol. 2002; 23: 1580-1588
        • Lubicz B.
        • Leclerc X.
        • Gauvrit J.Y.
        • Lejeune J.P.
        • Pruvo J.P.
        Endovascular treatment of intracranial aneurysms with matrix coils: a preliminary study of immediate post-treatment results.
        AJNR Am J Neuroradiol. 2005; 26: 373-375
        • Bavinzski G.
        • Richling B.
        • Binder B.R.
        • Gruber A.
        • Talazoglu V.
        • Dietrich W.
        • et al.
        Histopathological findings in experimental aneurysms embolized with conventional and thrombogenic/antithrombolytic Guglielmi coils.
        Minim. Invasive Neurosurg. 1999; 42: 167-174
        • Marx W.E.
        • Cloft H.J.
        • Helm G.A.
        • Short J.G.
        • Do H.M.
        • Jensen M.E.
        • et al.
        Endovascular treatment of experimental aneurysms by use of biologically modified embolic devices: coil-mediated intraaneurysmal delivery of fibroblast tissue allografts.
        AJNR Am J Neuroradiol. 2001; 22: 323-333
        • Dai D.
        • Ding Y.H.
        • Danielson M.A.
        • Kadirvel R.
        • Helm G.A.
        • Lewis D.A.
        • et al.
        Endovascular treatment of experimental aneurysms with use of fibroblast transfected with replication-deficient adenovirus containing bone morphogenetic protein-13 gene.
        AJNR Am J Neuroradiol. 2008; 29: 739-744
        • Chen Q.
        • Shou P.
        • Zhang L.
        • Xu C.
        • Zheng C.
        • Han Y.
        • et al.
        An osteopontin-integrin interaction plays a critical role in directing adipogenesis and osteogenesis by mesenchymal stem cells.
        Stem Cells. 2014; 32: 327-337
        • Bouzeghrane F.
        • Darsaut T.
        • Salazkin I.
        • Ogoudikpe C.
        • Gevry G.
        • Raymond J.
        Matrix metalloproteinase-9 may play a role in recanalization and recurrence after therapeutic embolization of aneurysms or arteries.
        J. Vasc. Interv. Radiol. 2007; 18: 1271-1279
        • Johnson J.L.
        • Dwivedi A.
        • Somerville M.
        • George S.J.
        • Newby A.C.
        Matrix metalloproteinase (MMP)-3 activates MMP-9 mediated vascular smooth muscle cell migration and neointima formation in mice.
        Arterioscler. Thromb. Vasc. Biol. 2011; 31: e35-e44
        • Taschner C.A.L.X.
        • Rachdi H.
        • Barros A.M.
        • Pruvo J.P.
        Matrix detachable coils for the endovascular treatment of intracranial aneurysms: analysis of early angiographic outcomes.
        Stroke. 2005; 36: 2176-2180
        • Rivet D.J.M.C.
        • Mazumdar A.
        • Pilgram T.K.
        • Derdeyn C.P.
        • Cross D.T.
        Single-institution experience with matrix coils in the treatment of intracranial aneurysms: comparison with same-center outcomes with the use of platinum coils.
        AJNR Am J Neuroradiol. 2007; 28: 1736-1742