In-stent restenosis (ISR) continues to require repeat revascularisation despite advances in stent design. Drug-coated balloon (DCB) therapy treats ISR by delivering an antiproliferative drug during brief balloon inflation while avoiding additional metal layers. Because effective therapy depends on efficient drug transfer during short balloon–artery contact, engineering the balloon–artery interface has been proposed to improve delivery. This study compared an investigational linear micro-patterned drug-coated balloon (LMDCB) with a comparator paclitaxel-coated DCB to determine whether micro-patterning enhances early biological efficacy in a porcine coronary ISR model.
The translational preclinical study used miniature pigs (~6 months old, 35–40 kg). Animals received aspirin (10 mg/day) and clopidogrel (75 mg/day) throughout. Sedation, anaesthesia, intraprocedural heparinisation, and postoperative care followed institutional standards. After ISR induction and confirmation at 4 weeks, paired ISR segments within each animal were randomised to LMDCB or comparator DCB. Two prespecified, independently analysed cohorts were enrolled: a 1-month cohort (n = 10 animals, 20 segments) to assess early biological response and a 3-month cohort (n = 4 animals, 8 segments) for mid-term context. Analyses were performed separately for each cohort.
ISR was created in two coronary arteries per animal by balloon overstretch injury (1.2:1 balloon-to-artery ratio for 60 seconds) followed by implantation of identical 3.0 × 18 mm bare-metal stents using an approximately 1.2× reference vessel diameter strategy. Lesion length was standardised by the 18-mm stent. After 4 weeks of ISR maturation, one vessel in each animal was treated with the LMDCB and the paired vessel with the comparator DCB. A 3.0 × 20 mm balloon was used for all treated segments, with an approximate 1.2 balloon-to-vessel sizing and a single 60-second inflation applied to both devices. LMDCB inflation was performed at the manufacturer-specified nominal pressure of 8 atm and the comparator at 7 atm.
The investigational LMDCB is a paclitaxel-coated balloon (3.0 µg/mm²) incorporating 16 longitudinal ridge-shaped linear micro-patterns approximately 130 µm in height. These ridges are designed to generate focal contact points at the balloon–artery interface during inflation. The comparator device was Pantera Lux (Biotronik), a clinically used paclitaxel-coated DCB with the same nominal drug dose density (3.0 µg/mm²) and a smooth, non-micropatterned surface. Coating chemistry and key device characteristics were summarised in the study’s device comparison table. The study notes that the proposed focal contact mechanism derives from device architecture and prior mechanistic work and was not directly measured in the present experiments.
Quantitative coronary angiography (QCA) was performed at ISR confirmation, immediately before and after DCB treatment, and at terminal follow-up. Minimum lumen diameter (MLD), reference diameter (RD), and percent diameter stenosis (%DS) were measured using automated edge-detection software; acute gain and late lumen loss were also defined. Optical coherence tomography (OCT) imaging was obtained with automated pullback and analysed at 1-mm intervals across the 20-mm stented segment. OCT-derived metrics included stent area, lumen area, neointimal area (stent area − lumen area), neointimal thickness, and percent area stenosis (%AS). QCA and OCT analyses were performed blinded to treatment allocation.
After terminal euthanasia, stented arteries were perfusion-fixed, embedded in resin, sectioned, and stained with haematoxylin–eosin and Masson’s trichrome. Histomorphometry measured lumen area, internal elastic lamina (IEL) area, and neointimal area (IEL area − lumen area). Percent area stenosis (%AS) was calculated from lumen and IEL areas. Semi-quantitative scores assessed arterial injury (Schwartz score), inflammation, endothelialisation, and fibrin deposition. Sections with severe artefacts were excluded. Histological analyses were performed blinded to treatment allocation.
The study employed paired within-animal comparisons with separate analyses for the 1-month and 3-month cohorts; no pooled analysis across cohorts was performed. A single explicit primary efficacy endpoint was not reported in the source text. The study focused on imaging and histological measures of neointimal proliferation and luminal dimensions, and statistical comparisons were reported for these endpoints.
In the 1-month cohort, LMDCB-treated segments showed statistically significant improvements in luminal dimensions and neointimal measures compared with the comparator paclitaxel-coated DCB. QCA: LMDCB had a larger MLD (2.3 ± 0.2 mm vs 1.9 ± 0.4 mm; p = 0.019) and lower percent diameter stenosis (13.3 ± 4.8% vs 23.7 ± 9.3%; p = 0.003). OCT: mean neointimal thickness was lower with LMDCB (0.2 ± 0.1 mm vs 0.3 ± 0.1 mm; p = 0.008). Histology: neointimal area was smaller with LMDCB (2.4 ± 0.7 mm² vs 2.9 ± 1.1 mm²; p = 0.011) and percent area stenosis lower (36.6 ± 10.4% vs 44.4 ± 17.8%; p = 0.013). Semi-quantitative vascular healing indices, including injury, inflammation, endothelialisation, and fibrin deposition scores, were reported as comparable between the two devices at 1 month. Procedural device-related complications were prospectively recorded; peri-procedural deaths that occurred during initial ISR induction were excluded because they preceded DCB exposure.
In the independently analysed 3-month cohort, QCA and OCT parameters were similar between LMDCB and comparator DCB. Exploratory histology in a limited subset suggested a larger lumen and lower percent area stenosis with LMDCB, but these histological findings were described as exploratory given the small sample size and were not the primary basis for efficacy conclusions at 3 months.
The LMDCB platform is intended to increase focal contact engagement through longitudinal ridges, thereby raising local contact pressure during inflation and facilitating contact-mediated paclitaxel transfer. This mechanism is supported by prior preclinical work showing increased contact pressure and greater short-term paclitaxel retention with earlier prototypes, but the present study did not directly evaluate device–tissue contact mechanics or drug-transfer kinetics.
Key limitations noted in the source text include the staged cohort design with separate terminal histology time points (precluding within-animal repeated histology), a small 3-month cohort limiting mid-term conclusions, and the absence of a single explicitly stated primary endpoint in the report. The mechanism of improved efficacy with LMDCB was not directly measured in this study and relies on device architecture and prior mechanistic reports. Findings from the 3-month cohort histology were described as exploratory due to sample size constraints.
In this porcine coronary ISR model, the investigational LMDCB was associated with reduced early neointimal proliferation and improved luminal dimensions at 1 month compared with a comparator paclitaxel-coated DCB, without evidence of impaired vascular healing. In a separately analysed 3-month cohort, imaging results were comparable between devices while histological comparisons were exploratory. The results support further evaluation of micro-patterned DCB surface engineering as a device-based approach to augment contact-mediated drug transfer in ISR, recognising that mechanistic confirmation and larger or longer-term studies would be required for translation to clinical practice.