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

Eric Kawamoto,Hank Hauser,Myles Greenberg,Jim Isaacson,Ronald Utecht,Rb Hayes,Andrew George Roberts,Katalin Kauser,Barb Haberer,Kevin S Warner,Blake Anderson,Dh Perkins,Robert Scott,Ann Spaans,Edgar Dalles Keyes

doi:10.3390/ijms23020683

Eric Kawamoto, Hank Hauser + Show 13 more

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https://doi.org/10.3390/ijms23020683

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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.

Highlights

The use and need for improved bioscaffolds in today’s medicine have increased dramatically with modern technology. It remains a challenge in cardiovascular tissue engineering to develop biomaterials which can simultaneously substitute for the biological and biomechanical functions of the natural extracellular matrix (ECM) of blood vessels
As described by Kelly et al [15], the 4-amino substituted 1, 8-naphthalimide core of 10-8-10 Dimer (Figure 1) is proposed to undergo photoexcitation upon blue-light illumination (450 nm) to generate a transient singlet excited state, 1[-10]*, which converts via intersystem crossing (ISC) to a triplet excited-state intermediate, 3[-10]*, (Figure 2, Equation (I))
Revascularization of the ischemic limb is the cornerstone of guideline-directed medical therapy [24,25]

Summary

Introduction

The use and need for improved bioscaffolds in today’s medicine have increased dramatically with modern technology. It remains a challenge in cardiovascular tissue engineering to develop biomaterials which can simultaneously substitute for the biological and biomechanical functions of the natural extracellular matrix (ECM) of blood vessels. In the blood vessel wall, ECM serves important structural and functional roles critical for the maintenance of vascular homeostasis and regeneration. It is a key regulator of cellular functions including phenotypic stability, proliferation and apoptosis of vascular cells [1]. Dysfunctional or damaged ECM is a source of pathological changes [2,3,4,5,6,7] and, not surprisingly, it is difficult to mimic the natural ECM by synthetic bioscaffolds [8]

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