Despite innovations in stent design, including reduction in strut thickness, novel antiproliferative agents, and more recently, the development of bioresorbable polymers, permanent metallic stents remain a nidus for sustained vascular inflammation, in-stent neoatherosclerosis, and impaired coronary vasomotor function. Therefore, the concept of a drug-eluting bioresorbable scaffold (BRS) with properties of medium-term temporary vascular scaffolding and long-term vascular reparative properties is appealing.
Several drug-eluting scaffolds, made of either biodegradable polymers or biocorrodible metals, have been developed and tested in first-in-man (FIM) studies showing comparable performance with current-generation drug-eluting stents (DES) in selected clinical subsets. More recently, large-scale randomized trials have demonstrated noninferiority of BRS compared to current-generation DES with respect to safety and efficacy. This cumulative evidence indicates the gradual maturation of the novel field of vascular reparative therapy.
RATIONALE FOR TRANSIENT BIORESORBABLE SCAFFOLDS
The impetus for developing drug-eluting BRS was driven by the need for more elastic and conformable platforms instead of stiff and permanent metallic implants to prevent acute and late recoil, seal post-procedural dissections derived from vascular barotrauma, and inhibit in-segment restenosis using appropriate drug elution.1 This technologic endeavor would overcome mid- and long-term effects of rigid metal caging over a previously pulsatile vascular tissue.
As early as 1996, van der Giessen et al2 reported on deploying synthetic polymer-based scaffolds in porcine coronary arteries. His preliminary observations demonstrated marked inflammatory reactions and subsequent intense neointimal proliferation. Further bench studies indicated that lower molecular weight polymers were an important determinant of these adverse vascular responses.2 Current polymeric BRSs are therefore engineered using high-molecular-weight polymers, with poly-L-lactic acid (PLLA) being the most commonly used material. Other polymeric BRSs include tyrosine-derived polycarbonates and poly(anhydride-esters) composed of salicylic acid. Furthermore, an alternative approach to polymeric materials has been the use of magnesium metallic alloys (Table 31-1). Long-term potential advantages of BRS over permanent metal stents have been proposed based on preliminary observations from multicenter registries.
Table 31-1Bioresorbable Coronary Scaffolds in Clinical Development ||Download (.pdf) Table 31-1 Bioresorbable Coronary Scaffolds in Clinical Development
Physiologic Restoration of Vascular Function
First- and second-generation metallic DESs have been associated with midterm endothelial dysfunction as well as a blunted vasodilatory response to endothelial-independent vasodilators such as nitroglycerine.3,4 Experimental models and clinical studies indicate that both polymeric and magnesium-based BRSs result in improved endothelial function, restoration of non–endothelial-dependent coronary vasoreactivity, and retained vessel pulsatility within and adjacent to the BRS deployed coronary segments.5,6 In addition to the pure biomechanical advantages of a more compliant platform, it is postulated that certain endothelial cell signaling and mechanotransduction pathways may be favorably affected by BRS. Finally, compensatory adaptive expansive remodeling with regression of plaque between the struts and the vessel wall resulting in incremental lumen gain ...