*2.2. Histomorphometric Results*

Following *ex vivo* studies, *in vivo* studies were performed using the rabbit ilio–femoral injury model to determine the impact of the KOS excipients on vascular remodeling. The animals were treated with a KOS-paclitaxel (*n* = 4), KOS-only balloon (*n* = 4), paclitaxel-only balloon (*n* = 4) or an uncoated balloon (*n* = 4). All arteries were treated successfully without any signs of dissection or thrombosis, and all animals survived the duration of the study. At 7 days, morphometric analysis demonstrated similar area measurements, including the EEL, IEL, lumen and media, for all treatment groups (Table 2). Neointimal thickness was significantly different between the varying groups (no coating: 0.10 ± 0.011 mm vs. KOS-only: 0.069 ± 0.022 mm vs. PXL-only: 0.066 ± 0.018 mm vs. KOS-PXL: 0.53 ± 0.003 mm, *p* = 0.005, Figure 3). Although percent area stenosis was the least in the KOS-PXL group, differences between the group were non-significant (no coating: 10.88% ± 4.52% vs. KOS-only: 9.99% ± 3.78% vs. PXL-only: 7.92% ± 3.84% vs. KOS-PXL: 6.80% ± 2.74%, *p* = 0.45).

**Table 2.** Summary of the morphometric and histological measurements in the rabbit iliac–femoral injury model.


Abbreviations: EEL—external elastic lamina, IEL—internal elastic lamina, EC—endothelial cell, SMC—smooth muscle cell.

**Figure 3.** Representative images of the arterial response following the varying treatment groups. H&E staining demonstrated neointimal growth for (**A**) the uncoated balloon group, (**B**) keratose-only coated balloon, (**C**) paclitaxel-only coated balloon and (**D**) keratose–paclitaxel coated balloon at 7 days. Neointimal growth is marked by double-arrow heads.

Histological analysis demonstrated minimal injury for all groups at 7 days with the greatest endothelial cell loss in the KOS–paclitaxel treated arteries (no coating: 0.25 ± 0.50 vs. KOS-only: 0.00 ± 0.00 vs. PXL-only: 0.25 ± 0.58 vs. KOS-PXL: 1.50 ± 0.58, *p* = 0.013). Inflammation was minimal for all groups and there was a trend towards greater SMC loss in the KOS–paclitaxel group (no coating: 0.00 ± 0.00 vs. KOS-only: 0.00 ± 0.00 vs. PXL-only: 0.25 ± 0.50 vs. KOS-PXL: 1.00 ± 0.82, *p* = 0.45). No aneurysmal dilatation or thrombosis was observed in any treated artery.
