Natural Vascular Scaffolding for Treatment of Femoropopliteal Lesions in Peripheral Arterial Disease

Purpose: Percutaneous transluminal angioplasty (PTA) is routinely performed in patients with peripheral artery disease (PAD); however, results are frequently suboptimal because of vessel recoil and dissection. The use of provisional stenting to address suboptimal results is associated with in-stent restenosis and fractures. Natural vascular scaffolding (NVS) is a novel treatment approach using photoactivated crosslinking of native extracellular matrix (ECM) proteins in the vessel wall, creating an endogenous scaffold instead of stent implants.

Materials and Methods: NVS therapy delivers a light activatable small molecule locally to the arterial wall. A light fiber inserted into the PTA balloon guidewire lumen is illuminated using 450-nm blue light from a laser source. Using fluorescence microscopy, the compound distribution is quantified on histologic sections in both porcine and cadaver arteries. The structure of the ECM proteins was visualized using multiphoton imaging of histologic sections. After angioplasty, 30% overstretch vessel diameters were recorded by quantitative contrast angiography in swine models. Additionally, biomechanical properties after NVS treatment were investigated in vitro in a porcine carotid artery model. Treatment safety was evaluated using primary human vascular cell culture and freshly obtained diseased vascular segments from human donors in organ culture and using isometric tension measurement.

Results: Fluorescent microscopy documented robust immediate uptake of the compound into and through the targeted arterial wall. Covalent links between ECM proteins caused by the photoactivation of the compound led to an increase in the density of the vessel wall as quantified by multiphoton imaging. Histologic changes included an elongated appearance of elastin in the vessel wall after overstretch correlating with the angiographic appearance of the treated artery in vivo. Acute retention of post-PTA luminal gain was maintained over 5 hours post-overstretch. In addition, the absence of PTA-induced vascular smooth muscle injury and vessel wall inflammation has been established in fresh ex vivo human popliteal arteries.

Conclusions: NVS therapy is a novel treatment in development that restores the lumen to provide immediate and sustainable blood flow increase without implants, offering a safer alternative to stent for patients with PAD.