Smart materials strategy for vascular challenges targeting in-stent restenosis: a critical review

Abstract

In-stent restenosis (ISR) presents a major challenge in vascular disease management, often leading to complications and repeated interventions. This review article explores the potential of existing smart materials strategies in addressing ISR, emphasizing advancements in materials science and biomedical engineering. We focus on innovative solutions such as bioactive coatings and responsive polymers that offer targeted responses to ISR-related internal and external triggers. These smart materials can dynamically adapt to the physiological conditions within blood vessels, responding in real time to various stimuli such as pH, oxidative stress and temperature. Moreover, we discuss preclinical progress and translational challenges associated with these materials as they move toward clinical applications. The review highlights the importance of controlled drug release and the need for materials that can degrade appropriately to minimize adverse effects. This work aims to identify critical research gaps and provide guidance to encourage interdisciplinary efforts to advance the development of smart stent technologies. Ultimately, the goal is to improve patient outcomes in vascular interventions by leveraging the capabilities of intelligent biomaterials to enhance ISR management and ensure better long-term efficacy and safety in-stent applications.

Keywords: in-stent restenosis; smart materials; targeted responses; triggers.

Graphical abstract

Figure 1.

Pathways leading to in-stent restenosis via pH changes in vascular microenvironments.

Figure 2.

Stimuli-responsive linkages in smart materials for targeted healing of in-stent restenosis.

Figure 3.

Solvent-responsive behavior of BSMF6-6b stent in alcohol and water. (A) Reversible coiling and expansion of the BSMF6-6b stent, coiling in alcohol within 300 seconds and expanding in water within 210 seconds. (B) Ex vivo application in a porcine heart model: S1 shows plaque in the artery; S2 shows the closed stent delivered via catheter; S3 shows stent expansion in water, compressing the plaque and restoring vessel patency. Adapted with permission from Shi et al. [93].

Figure 4.

NIR-triggered shape memory effect in SMP-based vascular stents. (A) Stepwise thermal programming and recovery of SMP showing reconfiguration at 120°C, shape programming at 0°C, and shape recovery at 60°C. (B) Time-sequence images of SMP under NIR light (808 nm) showing shape recovery from a programmed state to its original shape within 60 seconds, demonstrating the material’s responsiveness and potential for repeatable stent expansion in vascular applications. Adapted with permission from Liang et al. [95].

Figure 5.

Magnetically controlled soft robot design and performance in complex vascular pathways. (A) CAD model and prototype of a magnetically actuated soft robot with a stent-like structure, designed for precise navigation and controlled radial expansion under an external magnetic field (1.8 T). (B) Demonstration of robot navigation through a tortuous vascular model with a flow rate of 12 ml/min, illustrating adaptability to complex paths. (C) Real-time ultrasound imaging of the robot in an ex vivo porcine vascular model, showing deployment and tracking over time with contrast agent-enhanced visibility. Adapted with permission from Wang et al. [102].

Figure 6.

Ultrasound-responsive microcapsules for targeted drug release. (Aa) Schematic of microbubble-assisted drug delivery system, illustrating a vascular stent with microbubble-encapsulated PLGA-paclitaxel (PLGA-PTX) particles, guided to the target area using magnetic nanoparticles (Fe₃O₄) and activated by ultrasound. (Ab) Quantification of PTX content loaded in microbubbles at different preparation volumes, demonstrating scalable drug loading. (Ac) Cumulative PTX release profile over time, showing sustained drug release. (Ad) Cumulative PTX release under various ultrasound cycles and pressures, indicating controlled release with increased cycles and pressure. Adapted with permission from Wang et al. [113] (Ba) Cross-sectional view of ultrasound-responsive microcapsule with a dextran core containing the drug payload, surrounded by a PEGDA shell, designed to restrict passive drug release. (Bb) Illustration of focused ultrasound (FUS) activation, where the ultrasound transducer selectively targets microcapsules, triggering cavitation within the dextran core. (Bc) Release of drug payload post-ultrasound activation, illustrating the mechanism for on-demand drug delivery. Adapted with permission from Field et al. [111].

Figure 7.

Development and manufacturing of electro-responsive 3D-printed stents using conductive polymer composites. (A) Chemical structure of PEDOT:PSS for enhanced solubility and conductivity. (B) Preparation of PEDOT:PSS/TPU composite with embedded drug molecules for controlled release. (C) CAD modeling and 3D printing process for creating stents. (D) Schematic of the 3D tubular printer mechanism employing PCL/PLA composite materials. Adapted with permission from Alkahtani et al. [121] and Guerra et al. [126].