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

• Published in: International journal of molecular sciences 2022-01, Vol.23 (2), p.683
• Main Authors: Kauser, Katalin, Warner, Kevin S, Anderson, Blake, Keyes, Edgar Dalles, Hayes, R B, Kawamoto, Eric, Perkins, D H, Scott, Robert, Isaacson, Jim, Haberer, Barb, Spaans, Ann, Utecht, Ronald, Hauser, Hank, Roberts, Andrew George, Greenberg, Myles
• Format: Article
• Language: English
• Subjects: Amino acids; Angioplasty; Angioplasty, Balloon; Animals; Arteries - physiology; Arteriosclerosis; Atherosclerosis; Biomechanical Phenomena; Biomechanics; Blood Vessel Prosthesis; Blood vessels; Carotid arteries; Chemical bonds; Collagen; Cross-Linking Reagents - chemistry; Dimerization; Experiments; Extracellular matrix; Extracellular Matrix - radiation effects; Health services; Hypercholesterolemia - diagnostic imaging; Hypercholesterolemia - physiopathology; Hypercholesterolemia - therapy; Implants; Light; Microscopy; natural vascular scaffolding; Peptides - chemistry; Perfusion; photoactivated linking; Proteins; Retention; Scaffolding; Scaffolds; Stenosis; Stents; Swine; Tissue engineering; Tissue Scaffolds - chemistry; Vascular diseases; vascular wall; Veins & arteries
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23020683

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.