Advances in Engineering Venous Valves: The Pursuit of a Definite Solution for Chronic Venous Disease

Abstract

Native venous valves enable proper return of blood to the heart. Under pathological conditions (e.g., chronic venous insufficiency), venous valves malfunction and fail to prevent backward flow. Clinically, this can result in painful swelling, varicose veins, edema, and skin ulcerations leading to a chronic wound situation. Surgical correction of venous valves has proven to drastically reduce these symptoms. However, the absence of intact leaflets in many patients limits the applicability of this strategy. In this context, the development of venous valve replacements represents an appealing approach. Despite acceptable results in animal models, no venous valve has succeeded in clinical trials, and so far no single prosthetic venous valve is commercially available. This calls for advanced materials and fabrication approaches to develop clinically relevant venous valves able to restore natural flow conditions in the venous circulation. In this study, we critically discuss the approaches attempted in the last years, and we highlight the potential of tissue engineering to offer new avenues for valve fabrication.

Understanding Chronic Venous Disease: A Critical Overview of Its Pathophysiology and Medical Management

“…One of the most used, foam sclerotherapy, may benefit patients for some 5 years [ 329 ], though a higher success rate is reported with complementary techniques, such as catheter foam sclerotherapy with tumescence and irrigation [ 37 ]. For its part, tissue engineering is facing approaches in valve development for replacement, finding adequate materials to reach desired outcomes [ 330 ]. In the diagnosis area, new ultrasound technologies are more sophisticated and effective, enabling to reach better visualizations of blood flow, and diameter and compressibility in veins, which could provide an earlier diagnostic [ 331 ].…”

Glutaraldehyde fixation of venous valve tissue: A benchmark for alternative fixation methods

“…As such, past attempts at a bioprosthetic venous valve comprised of glutaraldehyde fixed xenografts have exhibited insufficient valve competency and high failure rates. 4,7…”

“…[1][2][3] Numerous bioprosthetic venous valves have been developed with an aim to restore valve function; however, long-term patency remains a challenge. [4][5][6][7][8] Calcification is a common issue with bioprosthetic valves and is influenced by the method of xenograft fixation, most notably glutaraldehyde. Glutaraldehyde is the standard fixative for cardiac valve applications and has been highly associated with calcification issues long-term due to phospholipids, free aldehyde groups, and residual antigenicity.…”

“…As such, past attempts at a bioprosthetic venous valve comprised of glutaraldehyde fixed xenografts have exhibited insufficient valve competency and high failure rates. 4,7 While the specific effects of glutaraldehyde fixation on the functional properties of cardiac tissue have been studied extensively, little to no information exists on glutaraldehyde fixation of venous tissue despite its continual use in bioprosthetic venous valves. 7,19 This hinders the development of an optimal alternative to glutaraldehyde fixation for venous valves and limits the options for improvement of bioprosthetic longevity.…”

“…4,7 While the specific effects of glutaraldehyde fixation on the functional properties of cardiac tissue have been studied extensively, little to no information exists on glutaraldehyde fixation of venous tissue despite its continual use in bioprosthetic venous valves. 7,19 This hinders the development of an optimal alternative to glutaraldehyde fixation for venous valves and limits the options for improvement of bioprosthetic longevity. The purpose of this study was to evaluate functional properties, specifically the degree of crosslinking and stability, of venous valve tissue fixed with glutaraldehyde to provide a benchmark for comparison in the development of alternative fixation methods.…”