Development of Organic/Inorganic Hybrid Materials for Fully Degradable Reactive Oxygen Species-Releasing Stents for Antirestenosis

Despite innovative advances in stent technology, restenosis remains a crucial issue for the clinical implantation of stents. Reactive oxygen species (ROS) are known to potentially accelerate re-endothelialization and lower the risk of restenosis by selectively controlling endothelial cells and smooth muscle cells. Recently, several studies have been conducted to develop biodegradable polymeric stents. As biodegradable polymers are not electrically conductive, double metallic layers are required to constitute a galvanic couple for ROS generation. Here, we report a new biodegradable hybrid material composed of a biodegradable polymer substrate and double anodic/cathodic metallic layers for enhancing re-endothelialization and suppressing restenosis. Pure Zn and Mg films (3 μm thick) were deposited onto poly-l-lactic acid (PLLA) substrates by DC magnetron sputtering, and a long-term immersion test using biodegradable hybrid materials was performed in phosphate-buffered solution (PBS) for 2 weeks. The concentrations of superoxide anions and hydrogen peroxide generated by the corrosion of biodegradable metallic films were monitored every 1 or 2 days. Both superoxide anions and hydrogen peroxide were seamlessly generated even after the complete consumption of the anodic Mg layer. It was confirmed that the superoxide anions and hydrogen peroxide were formed not only by the galvanic corrosion between the anode and cathode layers but also by the corrosion of a single Mg or Zn layer. The corrosion products of the Mg and Zn films in PBS were phosphate, oxide, or chloride of the biodegradable metals. Thus, it is concluded that ROS generation by the corrosion of PLLA-based hybrid materials can be sustained until the exhaustion of the cathode metal layer

Interface Engineering of Fully Metallic Stents Enabling Controllable H₂O₂ Generation for Antirestenosis

Despite significant advances in the design of metallic materials for bare metal stents (BMSs), restenosis induced by the accumulation of smooth muscle cells (SMCs) has been a major constraint on improving the clinical efficacy of stent implantation. Here, a new strategy for avoiding this issue by utilizing hydrogen peroxide (H2O2) generated by the galvanic coupling of nitinol (NiTi) stents and biodegradable magnesium–zinc (Mg–Zn) alloys is reported. The amount of H2O2 released is carefully optimized via the biodegradability engineering of the alloys and by controlling the immersion time to selectively inhibit the proliferation and function of SMCs without harming vascular endothelial cells. Based on demonstrations of its unique capabilities, a fully metallic stent with antirestenotic functionality was successfully fabricated by depositing Mg layers onto commercialized NiTi stents. The introduction of surface engineering to yield a patterned Mg coating ensured the maintenance of a stable interface between Mg and NiTi during the process of NiTi stent expansion, showing high feasibility for clinical application. This new concept of an inert metal/degradable metal hybrid system based on galvanic metal coupling, biodegradability engineering, and surface patterning can serve as a novel way to construct functional and stable BMSs for preventing restenosis

Selective Cell–Cell Adhesion Regulation via Cyclic Mechanical Deformation Induced by Ultrafast Nanovibrations

The adoption of dynamic mechanomodulation to regulate cellular behavior is an alternative to the use of chemical drugs, allowing spatiotemporal control. However, cell-selective targeting of mechanical stimuli is challenging due to the lack of strategies with which to convert macroscopic mechanical movements to different cellular responses. Here, we designed a nanoscale vibrating surface that controls cell behavior via selective repetitive cell deformation based on a poroelastic cell model. The vibrating indentations induce repetitive water redistribution in the cells with water redistribution rates faster than the vibrating rate; however, in the opposite case, cells perceive the vibrations as a one-time stimulus. The selective regulation of cell–cell adhesion through adjusting the frequency of nanovibration was demonstrated by suppression of cadherin expression in smooth muscle cells (fast water redistribution rate) with no change in vascular endothelial cells (slow water redistribution rate). This technique may provide a new strategy for cell-type-specific mechanical stimulation