Creating a Natural Vascular Scaffold by Photochemical Treatment of the Extracellular Matrix for Vascular Applications

Abstract

The development of bioscaffolds for cardiovascular medical applications, such as peripheral artery disease (PAD), remains to be a challenge for tissue engineering. PAD is an increasingly common and serious cardiovascular illness characterized by progressive atherosclerotic stenosis, resulting in decreased blood perfusion to the lower extremities. Percutaneous transluminal angioplasty and stent placement are routinely performed on these patients with suboptimal outcomes. Natural Vascular Scaffolding (NVS) is a novel treatment in the development for PAD, which offers an alternative to stenting by building on the natural structural constituents in the extracellular matrix (ECM) of the blood vessel wall. During NVS treatment, blood vessels are exposed to a photoactivatable small molecule (10-8-10 Dimer) delivered locally to the vessel wall via an angioplasty balloon. When activated with 450 nm wavelength light, this therapy induces the formation of covalent protein–protein crosslinks of the ECM proteins by a photochemical mechanism, creating a natural scaffold. This therapy has the potential to reduce the need for stent placement by maintaining a larger diameter post-angioplasty and minimizing elastic recoil. Experiments were conducted to elucidate the mechanism of action of NVS, including the molecular mechanism of light activation and the impact of NVS on the ECM.

Photochemically Aided Arteriovenous Fistula Creation to Accelerate Fistula Maturation

“…However, it is conceivable that the new covalent bonds introduce structural changes to the balloon-distended ECM, which drive these processes by modifying the integrin signaling in response to the hemodynamic changes following fistula surgery. Previous studies, using the photochemical treatment with the 10-8-10 Dimer, found altered structural appearance of ECM proteins and reduced ECM protein fragmentation, suggesting that the treatment provides lasting structural changes and resistance against matrix degrading enzymes [14].…”

“…ECM proteins, such as collagen fibers, elastin, and proteoglycans, are the major structural proteins of blood vessel walls. They convert mechanical stimuli generated by hemodynamic forces into biological signals via integrin-mediated mechanotransduction [14]. The integrity or reorganization…”

“…ECM proteins, such as collagen fibers, elastin, and proteoglycans, are the major structural proteins of blood vessel walls. They convert mechanical stimuli generated by hemodynamic forces into biological signals via integrin-mediated mechanotransduction [14]. The integrity or reorganization of this local cellular environment is largely responsible for the adequate regulation of cell responses as the system adjusts to hemodynamic changes produced by gradually developing stenotic changes or acute surgical interventions, thereby determining the outcome of long-term vascular remodeling [13,23].…”

“…Alucent Biomedical is focusing on targeting the vascular ECM as a therapeutic approach using a unique coated balloon device-called vessel restoration system for AVF creation (VRS-AVF)-to improve fistula maturation (Figure 1). Light activation of a small molecule 10-8-10 Dimer (polyetheramine-4-amino-1,8-naphtalamide) at the time of balloon inflation results in a photochemical reaction facilitating new covalent bond formation among oxidizable amino acids of the ECM proteins of the vein wall, retaining the size of the balloon distension [14][15][16]. Alteration in the ECM environment of cells regulates vascular responses, and it is responsible for adaptive or maladaptive remodeling of the vascular wall [17,18].…”

Therapeutic strategies based on non-ionizing radiation to prevent venous neointimal hyperplasia: the relevance for stenosed arteriovenous fistula, and the role of vascular compliance

“…There is nothing “natural” in the concept, as the photosensitizer is a substance fully synthesized in laboratory, the radiation (wavelength 400–525 nm) is generated by manufactured instruments (xenon lamps or lasers), and luminal pre-dilation (which is crucial to the main application of the procedure) is achieved by standard balloon angioplasty. The procedure was initially intended to replace percutaneous transluminal angioplasty/stenting as a treatment for peripheral artery disease ( 106 ). It was claimed ( 105 ) that because only a limited number of crosslinks are produced in collagen, the resulting stent-like constructs will be not as rigid as the stents in current use.…”