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

Abstract

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.