## 1 Introduction
### Unresolved Challenges in the Treatment of Neointimal Hyperplasia  
Plain old balloon angioplasty (POBA) was first performed in the 1970s as a revolutionary alternative to coronary artery bypass graft surgery (CABG). However, coronary POBA was associated with a high risk of NIH, sudden vessel closure, and elastic recoil. As a result, many patients underwent open-heart surgery due to these abrupt issues [11; 12]. In the mid-1980s, a self-expandable stent known as Wallstent(tm) attempted to address these issues. However, by 1991, Wallstent(tm) stents were withdrawn from the market due to technical challenges with their delivery system. This remains an ongoing challenge when targeting culprit lesions in difficult-to-access vessel segments [13]. Johnson & Johnson(tm) developed the first bare metal stent (BMS) in the 1980s, which became the first FDA-approved metal stent over balloon. The use of BMS significantly decreased the incidence of vascular recoil and restenosis to 17-44% compared to POBA [12; 13]. However, BMS did not fully resolve  
Figure 1: Illustration of the impact imposed by PCI, grafting, and DES. PCI and grafting may cause procedure-related injury to the vascular wall. Such injury can initiate an inflammatory cascade, which causes VSMCs to proliferate and migrate at the intimal layer. This leads to the development of NIH and/or ISR. Current available DESs effectively reduce the risk of restenosis; however, they can obstruct the endothelial healing process, increasing the risk of stent thrombosis. the issue, as it could still induce NIH in up to 30% of patients [14]. This often required urgent and costly repeat interventions of PCI to re-open the re-stenotic BMS. The drawbacks of BMS paved the way for the development of drug eluting stents (DESs). Stents coated with an antiproliferative drug in the early 2000s revolutionised the field of PCI. DESs have evolved through multiple generations. First-generation DES strut structures were fabricated of stainless steel and were coated with either the mTOR inhibitor rapamycin (Sirolimus) or the anti-tubulin paclitaxel (Taxol). Second-generation DES used cobalt-chromium struts and memory metals such as nitinol, which were coated with everolimus or zotarolimus. This generation benefited from reduced strut thickness, which improved flexibility, biocompatibility, and better eluting characteristics [15]. The most common advantage of DESs is their ability to lower the incidence of lumen re-blockage to approximately 10% [16; 17]. Despite this benefit, while DES can potentially reduce the risk of early restenosis and NIH, clinical trials have reported manifestations of late (>30 days) and very late (>12 months) stent thrombosis. This is owed to the antiproliferative drugs in DES, whose drug release kinetics can mismatch with the evolving pathology while slowing down the process of stent endothelization [14]. Once the systemic antiplateletts course therapy is completed, the uncovered parts of the strut can trigger an inflammatory response and lead to late stent thrombosis, which remains a challenge. Third-generation DESs were the bioabsorbable scaffold made from dissolvable polylactic acid (PLA). These emerged to avoid the lifetime implantation of conventional stents due to their ability to completely degrade within the body tissue. Randomised trials such as ABSORB II, ABSORB III, ABSORB China, and ABSORB, Japan, concluded that biosensorble stents were associated with high rates of intrasent strut scaffold collapse that promoted thrombosis, and the trials were stopped [17]. In contrast, stent technologies continue to be used in combination with polytetrafluoroethylene (PTFE) AVGs. The creation of AVGs is susceptible to failure as a result of venous-induced NIH followed by thrombosis. Currently, graft failure cannot be easily treated; however, the placement of another intragraft inside the original within or across the culprit lesion is now common. The Gore Viabhan(tm) stent graft endoprosthesis technology has been a highly effective solution.