Metallic stents are commonly used to promote revascularization and maintain patency of plaqued or damaged arteries following balloon angioplasty. To mitigate the long-term side effects associated with corrosion-resistant stents (i.e. chronic inflammation and late stage thrombosis), a new generation of so-called “bioabsorbable” stents is currently being developed. The bioabsorbable coronary stents will corrode and be absorbed by the artery after completing their task as vascular scaffolding. Research spanning the last two decades has focused on biodegradable polymeric, iron-based, and magnesium-based stent materials. The inherent mechanical and surface properties of metals make them more attractive stent material candidates than their polymeric counterparts. Unfortunately, iron produces a voluminous, retained oxide product in the arterial wall, whereas magnesium and its alloys corrode too rapidly. A third class of metallic bioabsorbable materials that are based on zinc has been introduced in the last few years. As summarized in this contribution, this new zinc-based class of materials demonstrates the potential for an absorbable metallic stent with the mechanical and biodegradation characteristics required for optimal stent performance. They appear to be free of flaws that limit the application of iron- and magnesium-based alloys, and polymers. This review compares bioabsorbable materials and summarizes progress towards bioabsorbable stents. It emphasizes on current understanding of physiological and biological benefits of zinc and its biocompatibility. Finally, the review provides an outlook on challenges in designing zinc-based stents of optimal mechanical properties and biodegradation rate.
The application of cell-derived extracellular matrix (ECM) in tissue engineering has gained increasing interest because it can provide a naturally occurring, complex set of physiologically functional signals for cell growth. The ECM scaffolds produced from decellularized fibroblast cell sheets contain high amounts of ECM substances, such as collagen, elastin, and glycosaminoglycans. They can serve as cell adhesion sites and mechanically strong supports for tissue-engineered constructs. An efficient method that can largely remove cellular materials while maintaining minimal disruption of ECM ultrastructure and content during the decellularization process is critical. In this study, three decellularization methods were investigated: high concentration (0.5 wt%) of sodium dodecyl sulfate (SDS), low concentration (0.05 wt%) of SDS, and freeze-thaw cycling method. They were compared by characterization of ECM preservation, mechanical properties, in vitro immune response, and cell repopulation ability of the resulted ECM scaffolds. The results demonstrated that the high SDS treatment could efficiently remove around 90% of DNA from the cell sheet, but significantly compromised their ECM content and mechanical strength. The elastic and viscous modulus of the ECM decreased around 80% and 62%, respectively, after the high SDS treatment. The freeze-thaw cycling method maintained the ECM structure as well as the mechanical strength, but also preserved a large amount of cellular components in the ECM scaffold. Around 88% of DNA was left in the ECM after the freeze-thaw treatment. In vitro inflammatory tests suggested that the amount of DNA fragments in ECM scaffolds does not cause a significantly different immune response. All three ECM scaffolds showed comparable ability to support in vitro cell repopulation. The ECM scaffolds possess great potential to be selectively used in different tissue engineering applications according to the practical requirement.
Although corrosion resistant bare metal stents are considered generally effective, their permanent presence in a diseased artery is an increasingly recognized limitation due to the potential for long-term complications. We previously reported that metallic zinc exhibited an ideal biocorrosion rate within murine aortas, thus raising the possibility of zinc as a candidate base material for endovascular stenting applications. This study was undertaken to further assess the arterial biocompatibility of metallic zinc. Metallic zinc wires were punctured and advanced into the rat abdominal aorta lumen for up to 6.5 months. This study demonstrated that metallic zinc did not provoke responses that often contribute to restenosis. Low cell densities and neointimal tissue thickness, along with tissue regeneration within the corroding implant, point to optimal biocompatibility of corroding zinc. Furthermore, the lack of progression in neointimal tissue thickness over 6.5 months or the presence of smooth muscle cells near the zinc implant suggest that the products of zinc corrosion may suppress the activities of inflammatory and smooth muscle cells.
Zinc (Zn) and its alloys have recently been introduced as a new class of biodegradable metals with potential application in biodegradable vascular stents. Although an in vivo feasibility study pointed to outstanding biocompatibility of Zn-based implants in vascular environments, a thorough understanding of how Zn and Zn2+ affect surrounding cells is lacking. In this comparative study, three vascular cell types—human endothelial cells (HAEC), human aortic smooth muscle cells (AoSMC), and human dermal fibroblasts (hDF)—were studied to advance the understanding of Zn/Zn2+-cell interactions. Aqueous cytotoxicity using a Zn2+ insult assay resulted in LD50 values of 50 µM for hDF, 70 µM for AoSMC, and 265 µM for HAEC. Direct cell contact with the metallic Zn surface resulted initially in cell attachment, but was quickly followed by cell death. After modification of the Zn surface using a layer of gelatin—intended to mimic a protein layer seen in vivo—the cells were able to attach and proliferate on the Zn surface. Further experiments demonstrated a Zn dose-dependent effect on cell spreading and migration, suggesting that both adhesion and cell mobility may be hindered by free Zn2+.
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