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

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.

A novel photochemical cross-linking technology to improve luminal gain, vessel compliance, and buckling post-angioplasty in porcine arteries.

UNLABELLED: Development of substituted 1,8-naphthalimides for photochemical cross-linking of biomolecules is the focus of this research. This study describes limited cross-linking of collagen in the artery wall to control recoil and buckling in arteries following balloon angioplasty. Isolated porcine arteries were overstretched (25%) with balloon angioplasty (BA) +/- light-activated naphthalimide treatment (NVS). Lumen size and recoil were measured as retention of stretch after angioplasty. Cross-sectional compliance and distensibility coefficients were measured as slope of cross-sectional area versus increasing hydrostatic pressure. Buckling was measured, with 30% axial pre-stretch and 200 mmHg, as deviation from the center line. Electron microscopy evaluation of collagen fibers was conducted. RESULTS: Uninjured arteries have low compliance and low levels of buckling, whereas the BA-injured arteries demonstrated much greater compliance and buckling behavior. Treatment of the injured artery with NVS reduced buckling and demonstrated compliance midway between the two groups while retaining the increased luminal diameter imparted by angioplasty compared to untreated vessels. In summary, limited collagen cross-linking with NVS treatment resulted in lumen retention, as well as improved compliance without the accompanying rigidity and stiffness of conventional stent therapy or current cross-linking materials. This treatment shows great promise for dilation, repair and strengthening of arteries damaged by injury or vascular disease.