Micro‐CT and histopathology methods to assess host response of aneurysms treated with shape memory polymer foam‐coated coils versus bare metal coil occlusion devices

Abstract

Recent studies utilizing shape memory polymer foams to coat embolizing coils have shown potential benefits over current aneurysm treatments. In the current study utilizing a rabbit-elastase aneurysm model, the performance of test article (foam-coated coil [FCC]) and control (bare platinum coils [BPCs]) devices were compared at 30, 90, and 180 days using micro-CT and histological assessments. The host response was measured by identifying the cells regionally present within the aneurysm, and assessing the degree of residual debris and connective tissue. The 3D reconstructions of aneurysms provided context for histologic findings, and aided in the overall aneurysm assessment. At all time points, >75% of the cells categorized in each aneurysm were associated with a bioactive yet biocompatible host response (vs. the remainder of cells that were associated with acute inflammation). The extracellular matrix exhibited a transition from residual fibrin at 30 days to a greater degree of connective tissue at 90 and 180 days. Although the control BPC-treated aneurysms exhibited a greater degree of connective tissue at the earliest time point examined (30 days), by 180 days, the FCC-treated aneurysms had more connective tissue and less debris overall than the control aneurysms. When considering cell types and extracellular matrix composition, the overall host response scores were significantly better in FCC-treated aneurysms at the later time point. Based on the results of these metrics, the FCC device may lead to an advanced tissue remodeling response over BPC occlusion devices. K E Y W O R D Shealing metric, histopathology, micro-CT, occlusion devices, shape memory polymer

In vitro cytocompatibility testing of oxidative degradation products

“…One proposed application for this material is as a coating for an embolic coil that can be used in the occlusion of aneurysms. 16,17,34 In order to make a rough comparison of degradation product mass to tissue volume, we assumed an aneurysm diameter of 11 mm to represent an aneurysm larger than 92% of aneurysms in a clinical study. 35 To determine the amount of foam that would be present in this aneurysm, we assumed a packing density of 23% with foamcoated coil devices before the devices had expanded, which correlates with a packing density of ~58% after foam expansion, based on our previous work.…”

“…13 Polyurethane foams are one example of SMPs that is being investigated for use in medical devices, including potential applications such as embolic devices and tissue scaffolds. [14][15][16][17][18][19] SMP foams can be designed to be compressed in a low-profile secondary shape that enables minimally invasive delivery and actuation at body temperature. After serving their purpose in the specific application and allowing for the desired new tissue growth, these foams can be designed to degrade in the body.…”

Effect of pore size and spacing on neovascularization of a biodegradble shape memory polymer perivascular wrap

“…Inflammatory responses will continue for many months and through the full resorption of the scaffold. Consistent with classic remodeling and wound healing processes, however, 30 days has been shown with other, biodegradable (polyurethane‐based) SMPs to be an important transition phase where acute inflammatory reactions are still active, but begin to give way to macrophage‐directed remodeling to granulation tissue (Jessen et al, 2020). Indeed, it is generally known that key inflammatory and remodeling phases have peaked and/or are resolved by 3 weeks (Anderson, Rodriguez, & Chang, 2008; Li, Chen, & Kirsner, 2007).…”

Characterization of shape memory polymer foam hemostats in in vitro hemorrhagic wound models

“…Over 180 days of implantation in a rabbit elastase aneurysm model, SMP foams had comparable inflammation rates to platinum coil clinical controls 29 . Additionally, the overall host response scores to SMP foams were significantly better than those of platinum coil controls at 90 and 180 days 30 . In a porcine aneurysm model, SMP foams promoted stable clotting within the first hour of implantation 10 .…”

“…29 Additionally, the overall host response scores to SMP foams were significantly better than those of platinum coil controls at 90 and 180 days. 30 In a porcine aneurysm model, SMP foams promoted stable clotting within the first hour of implantation. 10 Almost complete healing was observed after 90 days with minimal inflammatory response.…”