Background Monocyte chemoattractant protein 1 (MCP-1) and osteopontin (OPN) have been identified separately as key mediators of the aneurysm healing process following coil embolization in the rodent model. The ability of protein coated coils to accelerate this process is currently unknown.
Objective To create coils coated with both MCP-1 and OPN to target aneurysm healing.
Methods We used a polymer (poly(glycolide-co-caprolactone)) (Rao pharmaceuticals) (CG910) to test whether coils could be dual coated with active proteins with sequential reliable release. Coils were coated with poly-DL-lactic glycolic acid (PLGA), CG910, and subsequently dipped with protein OPN (inner layer for delayed release) and MCP-1 (outer layer for initial release). Release assays were used to measure protein elution from coils over time. To test in vivo feasibility, coated coils were implanted into carotid aneurysms to determine the effect on aneurysm healing.
Results The in vitro protein release assay demonstrated a significant amount of OPN and MCP-1 release within 2 days. Using a 200 µg/µL solution of MCP-1 in phosphate-buffered saline, we showed that CG910 coated coils provide effective release of MCP over time. In the carotid aneurysm model, MCP-1 and OPN coated coils significantly increased tissue ingrowth (74% and 80%) compared with PLGA and CG910 coated coils alone (58% and 53%). To determine synergistic impact of dual coating, we measured ingrowth for MCP-1/OPN coils (63%) as well as overlap coefficients for NOX4 and NFκB with CD31.
Conclusions This study demonstrates that MCP-1 and OPN coated coils are viable and may promote early aneurysm healing. Dual coated coils may have synergistic benefit given different location of protein interaction measured in vivo. Further work is warranted.
- Inflammatory Response
Data availability statement
All data relevant to the study are included in the article or uploaded as supplementary information.
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Contributors All the authors have made substantial contributions to the acquisition, analysis, and data interpretation; drafting the work and making revisions; approving the final draft for submission; and are accountable for the integrity of the work presented. DL, BH, and KH made substantial contributions to the conception of the project. DL accepts full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish.
Funding This study was funded by SNIS (Fellow/Young Investigator Research Grant).
Competing interests DL received funding for this work provided by the SNIS fellow/young investigator research grant. BL-W received funding by the NIH R25 (ns108939-04). WSD has received funding from the brain aneurysm foundation and the NIH. KH has received funds from the brain aneurysm foundation and the NIH. BH and KH have an active patent undergoing review: “Methods, devices, and compositions for lesion repair and prevention.” BH has received funding from the NIH, SNIS, and brain aneurysm foundation. The work is further supported by funding from the Eblin Research Endowment, the Christine Desmond Fund, the James and Brigette Marino Family Professorship Endowment, and the St George Family Fund.
Provenance and peer review Not commissioned; externally peer reviewed.
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