---
title: "Linear micro-patterned drug-coated balloon reduces early neointimal growth in porcine coronary ISR"
id: "plos-one-16-surface-micro-patterned-drug-coated-balloon-enhances-early-biological-efficacy"
canonical_url: "https://medichelpline.com/clinical-feed/plos-one-16-surface-micro-patterned-drug-coated-balloon-enhances-early-biological-efficacy"
content_type: "clinical_feed_article"
specialty: "Cardiology"
source_name: "PLOS ONE (Medicine)"
source_url: "https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359232"
published_at: "2026-09-25T14:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Linear micro-patterned drug-coated balloon reduces early neointimal growth in porcine coronary ISR
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/plos-one-16-surface-micro-patterned-drug-coated-balloon-enhances-early-biological-efficacy
- **Specialty:** [Cardiology](https://medichelpline.com/clinical-feed/cardiology.md)
- **Primary Source:** PLOS ONE (Medicine)
- **Source URL:** [Original Journal Publication](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359232)
- **Published At:** 2026-09-25T14:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- This preclinical porcine coronary in-stent restenosis (ISR) study compared an investigational **linear micro-patterned drug-coated balloon (LMDCB)** with a comparator paclitaxel-coated DCB (Pantera Lux), both delivering 3.0 µg/mm² paclitaxel, using a paired within-animal design. - ISR was induced by balloon overstretch and implantation of 3.0 × 18 mm bare-metal stents; ISR matured for 4 weeks before paired treatment with LMDCB and comparator DCB in the same animal. - Two prespecified independent cohorts were studied: a 1-month cohort (10 animals, 20 treated segments) to evaluate early biological response and healing, and a 3-month cohort (4 animals, 8 treated segments) for supportive mid-term context; analyses were performed separately for each cohort. - Procedural protocol: 3.0 × 20 mm balloons, ~1.2:1 balloon-to-vessel sizing, single 60-second inflation; LMDCB inflated at 8 atm, comparator at 7 atm; animals received aspirin and clopidogrel throughout. - Imaging endpoints included **quantitative coronary angiography (QCA)** and **optical coherence tomography (OCT)**; histology and histomorphometry assessed neointimal area, percent area stenosis, vascular injury, inflammation, endothelialisation, and fibrin. - At 1 month, LMDCB-treated segments had larger minimum lumen diameter (MLD 2.3 ± 0.2 mm vs 1.9 ± 0.4 mm; p = 0.019), lower percent diameter stenosis (13.3 ± 4.8% vs 23.7 ± 9.3%; p = 0.003), lower mean neointimal thickness on OCT (0.2 ± 0.1 mm vs 0.3 ± 0.1 mm; p = 0.008), smaller neointimal area on histology (2.4 ± 0.7 mm² vs 2.9 ± 1.1 mm²; p = 0.011), and lower percent area stenosis by histology (36.6 ± 10.4% vs 44.4 ± 17.8%; p = 0.013). - Vascular healing indices (semi-quantitative histological scores for injury, inflammation, endothelialisation, and fibrin) were reported as comparable between devices at 1 month. - In the independent 3-month cohort, QCA and OCT parameters were similar between LMDCB and comparator DCB; exploratory histology in a limited subset suggested a trend toward larger lumen and lower percent area stenosis with LMDCB, but these findings were labelled exploratory. - The proposed mechanism — that LMDCB longitudinal ridges increase focal contact pressure and enhance contact-mediated paclitaxel transfer — is based on device architecture and prior mechanistic work and was not directly measured in this study. - Animal welfare: study approved by relevant IACUC, ARRIVE guidelines followed; initial 17 pigs were used, with exclusions for peri-procedural deaths prior to DCB exposure (final n = 14 completing follow-up).
## Clinical Analysis & Structured Key Points
Surface micro-patterned drug-coated balloon enhances early biological efficacy in a porcine coronary in-stent restenosis model | PLOS One Browse Subject Areas ? Click through the PLOS taxonomy to find articles in your field. For more information about PLOS Subject Areas, click here . Article Authors Metrics Comments Media Coverage Reader Comments Figures Figures Abstract Background Drug-coated balloon (DCB) therapy for in-stent restenosis (ISR) relies on efficient drug transfer during balloon–artery contact. Surface micro-patterning has been proposed to enhance transfer efficiency without altering the antiproliferative drug. This study evaluated a linear micro-patterned DCB (LMDCB) compared with a comparator paclitaxel-coated DCB in a porcine coronary ISR model. Methods ISR was induced by bare-metal stent implantation followed by a 4-week maturation period. In two prespecified cohorts (1 month: 10 animals, 20 segments; 3 months: 4 animals, 8 segments), paired ISR segments within each animal were treated with LMDCB or a comparator paclitaxel-coated DCB (3.0 µg/mm 2 ). Endpoints included quantitative coronary angiography (QCA), optical coherence tomography (OCT), and histology. Results At 1 month, LMDCB demonstrated a larger minimum lumen diameter (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 showed lower mean neointimal thickness (0.2 ± 0.1 mm vs 0.3 ± 0.1 mm; p = 0.008). Histology showed lower neointimal area (2.4 ± 0.7 mm 2 vs 2.9 ± 1.1 mm 2 ; p = 0.011) and percent area stenosis (36.6 ± 10.4% vs 44.4 ± 17.8%; p = 0.013), with comparable vascular healing indices. In the independent 3-month cohort, QCA and OCT findings were similar between groups. Exploratory histology in a limited subset suggested a larger lumen and lower percent area stenosis with LMDCB. Conclusions In this porcine coronary ISR model, LMDCB was associated with reduced neointimal proliferation and improved luminal dimensions at 1 month compared with a comparator paclitaxel-coated DCB, without impaired vascular healing. In a separate 3-month cohort, imaging findings were comparable between devices, while histology remained exploratory. Citation: Kim S, Lee S-G, Park J, Park J, Kim D-K, Kim K-H, et al. (2026) Surface micro-patterned drug-coated balloon enhances early biological efficacy in a porcine coronary in-stent restenosis model. PLoS One 21(9): e0359232. https://doi.org/10.1371/journal.pone.0359232 Editor: Prakash Sojitra, IPSurface Canada Inc, CANADA Received: April 9, 2026; Accepted: September 9, 2026; Published: September 25, 2026 Copyright: © 2026 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: All relevant data are within the paper and its Supporting Information files. Funding: This work was supported by grants from the National Research Foundation of Korea (NRF), funded by the Korean government (MSIT) (RS-2022NR070832 and RS-2023-00276320). Genoss Co., Ltd. provided the bare-metal stents used for ISR induction and the investigational linear micro-patterned drug-coated balloons free of charge. Neither the NRF/MSIT nor Genoss Co., Ltd. had any role in study design, data collection and analysis, data interpretation, decision to publish, or preparation of the manuscript. Competing interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Genoss Co., Ltd. provided the bare-metal stents used for ISR induction and the investigational linear micro-patterned drug-coated balloons free of charge. The company had no role in study design, data collection, data analysis, data interpretation, decision to publish, or preparation of the manuscript. The authors declare no other competing interests. There was no additional external funding received for this study. The authors declare no other competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no restrictions on the sharing of data or materials associated with this study. Introduction In-stent restenosis (ISR) remains a clinically relevant limitation of percutaneous coronary intervention despite advances in stent design and implantation techniques, and it continues to necessitate repeat revascularisation in a substantial proportion of patients [ 1 ]. Drug-coated balloon (DCB) therapy has emerged as an established treatment strategy for ISR by delivering an antiproliferative drug during brief balloon inflation while avoiding additional metallic layers, thereby preserving a leave-nothing-behind strategy in previously stented segments [ 2 – 4 ]. The therapeutic effectiveness of DCBs depends on efficient transfer of the antiproliferative drug from the balloon surface to the arterial wall during the short period of balloon–artery contact. However, ISR lesions often exhibit heterogeneous neointimal morphology and irregular luminal geometry within the stented segment, which may compromise uniform balloon apposition and limit local drug deposition despite an adequate nominal dose [ 1 , 5 , 6 ]. These considerations suggest that treatment outcomes may be influenced not only by the pharmacological agent but also by the efficiency of device–tissue interaction during balloon inflation. Consistent with this concept, comparative studies in coronary ISR have not identified a uniformly superior antiproliferative drug across current DCB platforms, and device-specific performance may also vary among balloons delivering the same drug but using different coating technologies or excipient formulations. Together, these observations support the view that coating–tissue interaction and delivery mechanics are important determinants of effective drug transfer and biological response beyond nominal drug dose alone [ 7 – 9 ]. Device-based engineering strategies aimed at optimising the balloon–artery interface may therefore represent a complementary approach to improving DCB performance. Linear micro-patterned drug-coated balloon (LMDCB) platforms incorporate longitudinal micro-architectural surface structures designed to increase focal contact engagement during balloon inflation and thereby facilitate drug transfer to the vessel wall. Prior preclinical work with an earlier prototype of this platform reported increased contact pressure and greater short-term paclitaxel retention in rabbit iliac arteries, together with favourable imaging findings in a limited minipig coronary ISR model [ 10 ]. The present study was designed to evaluate whether a linear micro-patterned DCB improves biological efficacy compared with a comparator paclitaxel-coated DCB in a porcine coronary ISR model . Using a paired within-animal design, we conducted a staged translational preclinical study with two prespecified, independently analysed follow-up cohorts. A 1-month cohort was used to evaluate the early biological response to treatment, while a separate 3-month cohort was included to provide supportive mid-term context regarding neointimal response and vascular healing. Methods Study design and ethical approval This staged translational preclinical study compared an investigational LMDCB with a comparator paclitaxel-coated DCB in a porcine coronary ISR model using a paired within-animal design. The 1-month and 3-month assessments were conducted sequentially in separately procured animal cohorts as part of a staged preclinical development programme. Separate cohorts were required because histological assessment at each follow-up time point involved terminal euthanasia and tissue harvesting; therefore, the same animals could not contribute histological data at both time points. The study was designed to evaluate the early biological response and vascular healing at 1 month and to provide supportive information regarding the vascular response and healing at a later follow-up time point. Accordingly, separate cohorts underwent terminal follow-up at 1 month (n = 10 animals) or 3 months (n = 4 animals) after DCB treatment. In each animal, ISR was created in two coronary arteries. After ISR confirmation at 4 weeks post-stenting, one vessel was treated with LMDCB and the paired vessel with the comparator DCB. The LMDCB and comparator DCB were assigned to the two paired coronary segments in a 1:1 ratio according to a randomisation schedule generated using a random-number table before the interventional procedures. Allocation was concealed from the interventional operator until the paired target segments had been selected and baseline angiographic and OCT assessments had been completed. The interventional operator became aware of device assignment during device preparation and was therefore not blinded during DCB deployment. Between-device comparisons were performed using paired observations within the same animal. Analyses were performed separately for the 1-month and 3-month cohorts, and no pooled analysis across follow-up cohorts was conducted. The study was approved by the Animal Ethics Committee and the Institutional Animal Care and Use Committee (IACUC) at the Cardiovascular Product Evaluation Center, Yonsei University College of Medicine (CPEC-IACUC-161007 and CPEC-IACUC-181003). Animal care complied with the Animal Welfare Act and the “Principles of Laboratory Animal Care” (NIH Publication No. 85−23, revised 1996). The study was conducted in accordance with the ARRIVE guidelines for reporting animal research. Animals and peri-procedural management Initially, 17 miniature pigs (approximately 6 months old; 35–40 kg) were used in this study. Miniature pigs were selected for their anatomical similarity to human coronary anatomy and adequate size for catheterisation. Aspirin (10 mg/day) and clopidogrel (75 mg/day) were administered throughout the study period. Animals were sedated with intramuscular atropine (0.05 mg/kg), tramadol (5 mg/kg), and Baytril (5 mg/kg). Induction anaesthesia included intravenous alfaxan (0.2 mg/kg) and rompun (0.05 mg/kg), and anaesthesia was maintained with 1.5% isoflurane in oxygen. Coronary access was obtained via the carotid artery. Unfractionated heparin (200 U/kg) was administered intraprocedurally to maintain an activated clotting time of approximately 250 seconds. Physiological monitoring was performed using the Mac-Lab system (GE, USA). All procedures were performed by researchers trained in animal care and handling. Postoperative analgesia was provided as needed during the recovery period. During the study period, the animals were housed under controlled conditions (12-hour light/dark cycle) with free access to food and water, and their health and behaviour were monitored daily. Humane endpoints were defined prior to study initiation, and criteria for early euthanasia included unexpected signs of severe distress, including laboured breathing, unresponsiveness, or prolonged anorexia or adipsia. If these criteria were met, the animal was to be euthanised immediately to prevent further suffering. Before ISR induction, 12 animals were allocated to the 1-month cohort and 5 to the 3-month cohort. Two animals in the 1-month cohort and one in the 3-month cohort died unexpectedly during or immediately after balloon overstretch injury and bare-metal stent implantation. These animals were excluded from follow-up. These deaths occurred approximately 4 weeks before DCB treatment and therefore before exposure to either the investigational LMDCB or the comparator DCB. The remaining 14 miniature pigs (10 in the 1-month cohort and 4 in the 3-month cohort) completed the planned follow-up without meeting the predefined criteria for early euthanasia. ISR induction protocol ISR was induced in two coronary arteries per animal (right coronary artery, left anterior descending artery, or left circumflex artery) by balloon overstretch injury followed by bare-metal stent (BMS) implantation. Balloon overstretch injury was performed using a 1.2:1.0 balloon-to-artery diameter ratio for 60 seconds. Subsequently, an identical 3.0 mm × 18 mm BMS (Genoss Co., Ltd., Seoul, Korea) was implanted in each target vessel using an approximately 1.2 × reference vessel diameter strategy; stent balloon inflation was repeated twice for 30 seconds each. Accordingly, lesion length was standardised by the implanted 18-mm stent and was therefore not analysed as an independent lesion characteristic. ISR was allowed to develop for 4 weeks and was confirmed by coronary angiography and OCT. DCB treatment protocol and follow-up DCB treatment was performed in both ISR vessels within each animal (LMDCB in one vessel and comparator DCB in the other). A 3.0 × 20 mm balloon was used for all treated segments in both the investigational LMDCB and comparator DCB groups, corresponding to an approximate balloon-to-reference vessel diameter ratio of 1.2 based on the angiographically measured reference vessel diameter. Balloon inflation was maintained for 60 seconds with a single inflation per vessel. A 60-second inflation duration has also been used in a randomised clinical study of coronary DCB treatment for ISR [ 3 ]. The same balloon dimensions, sizing approach, and single-inflation protocol were applied to both devices to preserve internal comparability. However, inflation duration and the use of repeat inflation may vary in clinical practice according to lesion and procedural characteristics. The investigational LMDCB is a paclitaxel-coated balloon (3.0 µg/mm²) featuring 16 conformal longitudinal ridge-shaped linear micro-patterns (height, 130 µm), as previously described [ 10 ]. These surface structures are designed to generate focal contact points at the balloon–artery interface during inflation, which may increase local contact pressure and facilitate contact-mediated paclitaxel transfer to the vessel wall. The comparator device was Pantera Lux (Biotronik, Bülach, Switzerland), a paclitaxel-coated DCB with the same nominal drug dose density of 3.0 µg/mm² and a smooth, non-micropatterned balloon surface. Pantera Lux was selected as the active comparator because it is a clinically used DCB that delivers the same antiproliferative drug at the same nominal dose density as the investigational LMDCB, thereby allowing comparison while matching drug identity and nominal dose density. A schematic and cross-sectional comparison of a flat-surfaced DCB and the LMDCB, together with the proposed focal contact-mediated drug-transfer mechanism, is shown in Fig 1 . Download: PNG larger image TIFF original image Fig 1. Schematic and cross-sectional comparison of a flat-surfaced drug-coated balloon and the linear micro-patterned drug-coated balloon. https://doi.org/10.1371/journal.pone.0359232.g001 A flat-surfaced DCB is depicted as having a broad balloon–artery contact interface, whereas the LMDCB incorporates 16 longitudinal ridge-shaped micro-patterns, approximately 130 µm in height, designed to generate focal contact points during inflation. These focal contact points may increase local contact pressure and facilitate contact-mediated drug transfer to the vessel wall. The proposed mechanism is based on the device architecture and prior mechanistic findings reported by Lee et al. [ 10 ] and was not directly evaluated in the present study. The schematic was newly created for the present study and is not to scale. DCB, drug-coated balloon; LMDCB, linear micro-patterned drug-coated balloon. The coating chemistry and key device characteristics of the LMDCB and comparator DCB are summarised in Table 1 . Each device was inflated at its respective manufacturer-specified nominal pressure: 8 atm for the LMDCB and 7 atm for the comparator DCB. Download: PNG larger image TIFF original image Table 1. Coating chemistry and key device characteristics of the LMDCB and comparator DCB. https://doi.org/10.1371/journal.pone.0359232.t001 Procedural device-related complications, including balloon rupture, coating detachment, shaft fracture, or incomplete balloon expansion, were prospectively recorded during each intervention. Animals continued dual antiplatelet therapy and were followed to terminal assessment at 1 month or 3 months after DCB treatment. At the terminal time point, animals were euthanised under deep anaesthesia via intravenous potassium chloride overdose. Quantitative coronary angiography (QCA) Coronary angiography was performed during ISR induction, including after stent implantation, and at the time of DCB treatment and follow-up. For QCA analysis, angiograms obtained immediately before DCB treatment (4 weeks after stent implantation), immediately after DCB treatment, and at terminal follow-up were analysed using the CAAS system (Pie Medical Instruments, the Netherlands). Minimum lumen diameter (MLD) and reference diameter (RD) were determined at end-diastole in matched projections using the software’s automated edge-detection algorithm. The RD was defined as the reconstructed diameter at the location of the MLD, as determined by the software’s interpolation algorithm. Percent diameter stenosis (%DS) was calculated as [(RD − MLD)/RD] × 100. Acute gain was defined as the MLD immediately after DCB treatment minus the MLD immediately before DCB treatment, and late lumen loss was defined as the MLD immediately after DCB treatment minus the MLD at follow-up. QCA analyses were performed by investigators blinded to treatment allocation. Optical coherence tomography (OCT) OCT imaging was acquired using the C7-XR system (LightLab Imaging Inc., St. Jude Medical, USA). Automated pullback was performed at 20 mm/s with an image acquisition rate of 100 frames/s. During imaging, the coronary lumen was cleared by continuous flushing of contrast media through the guiding catheter at 4 mL/s. Cross-sections were analysed at 1-mm intervals along the 20-mm stented segment. OCT-derived parameters included stent area, lumen area, neointimal area (stent area − lumen area), neointimal thickness, and percent area stenosis (%AS), calculated as [(stent area − lumen area)/stent area] × 100. All OCT analyses were performed offline by an experienced analyst blinded to treatment allocation. Histology, histomorphometry, and semi-quantitative healing assessment Following euthanasia, the harvested heart was perfusion-fixed by connecting a fixative tube to the aorta and applying 10% formalin at 100–130 mmHg for 24 hours. The stented arteries were embedded in resin (Technovit 7200 VLC; Kulzer, Wehrheim, Germany). Embedded blocks were cut into proximal, mid, and distal cross-sections (220 ± 20 µm) using a diamond cutting system (EXAKT 300 CP, Germany), mounted on glass slides using an adhesive press system (EXAKT 402, Germany), and ground to a final thickness of 35 ± 5 µm (EXAKT 400CS, Germany). Sections were stained with haematoxylin and eosin (H&E) and Masson's trichrome and examined by light microscopy. Sections with severe artefacts or incomplete stent strut representation were excluded from analysis. Quantitative histomorphometric analysis was performed to measure lumen area, internal elastic lamina (IEL) area, and external elastic lamina (EEL) area. Neointimal area was calculated as IEL area − lumen area, and percent area stenosis (%AS) as [1 − (lumen area/IEL area)] × 100 for each section. Semi-quantitative histological scoring was performed according to established grading systems: arterial injury was assessed using the Schwartz score (0–3) determined by the depth of injury relative to the IEL and media [ 11 ]; inflammation and endothelialisation scores were assessed using published criteria [ 12 ]; and fibrin deposition was scored from 0 to 3 as previously described [ 13 ]. Study endpoints Analyses were conducted separately for the 1-month and 3-month cohorts. A single primary efficacy endpoint was not explicitl
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