Lillian S Wells Department of Neurosurgery, University of Florida, Gainesville, Florida, USA
Lillian S Wells Department of Neurosurgery, University of Florida, Gainesville, Florida, USA.
J Neurointerv Surg. 2023 Jul;15(7):689-694. doi: 10.1136/neurintsurg-2022-018710. Epub 2022 May 24.
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.
To create coils coated with both MCP-1 and OPN to target aneurysm healing.
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.
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.
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.
单核细胞趋化蛋白 1（MCP-1）和骨桥蛋白（OPN）已分别被确定为在啮齿动物模型中线圈栓塞后动脉瘤愈合过程的关键介质。目前尚不清楚涂覆有蛋白质的线圈是否能够加速这一过程。
用 MCP-1 和 OPN 来制作涂覆有蛋白质的线圈以促进动脉瘤愈合。
我们使用聚合物（聚（乙交酯-co-己内酯））（Rao 制药公司）（CG910）来测试线圈是否可以用活性蛋白进行双重涂覆，并进行可靠的顺序释放。线圈涂覆有聚-DL-乳酸-乙醇酸（PLGA）、CG910，然后用 OPN（内层用于延迟释放）和 MCP-1（外层用于初始释放）进行浸涂。释放试验用于测量随时间从线圈洗脱的蛋白质。为了测试体内的可行性，将涂覆的线圈植入颈动脉动脉瘤中，以确定对动脉瘤愈合的影响。
体外蛋白质释放试验表明，在 2 天内有大量的 OPN 和 MCP-1 释放。使用 200µg/µL 的 MCP-1 磷酸盐缓冲液溶液，我们表明 CG910 涂覆的线圈可以随着时间的推移有效地释放 MCP。在颈动脉动脉瘤模型中，与单独使用 PLGA 和 CG910 涂覆的线圈相比，MCP-1 和 OPN 涂覆的线圈显著增加了组织向内生长（74%和 80%）。为了确定双重涂覆的协同作用，我们测量了 MCP-1/OPN 线圈的向内生长（63%）以及体内测量的 NOX4 和 NFκB 与 CD31 的重叠系数。
本研究表明，MCP-1 和 OPN 涂覆的线圈是可行的，可能会促进早期动脉瘤愈合。鉴于体内测量到的蛋白质相互作用的位置不同，双重涂覆的线圈可能具有协同作用。还需要进一步的研究。
