Engineering Efforts to Refine Compatibility and Duration of Aortic Valve Replacements: An Overview of Previous Expectations and New Promises

Abstract

The absence of pharmacological treatments to reduce or retard the progression of cardiac valve diseases makes replacement with artificial prostheses (mechanical or bio-prosthetic) essential. Given the increasing incidence of cardiac valve pathologies, there is always a more stringent need for valve replacements that offer enhanced performance and durability. Unfortunately, surgical valve replacement with mechanical or biological substitutes still leads to disadvantages over time. In fact, mechanical valves require a lifetime anticoagulation therapy that leads to a rise in thromboembolic complications, while biological valves are still manufactured with non-living tissue, consisting of aldehyde-treated xenograft material (e.g., bovine pericardium) whose integration into the host fails in the mid- to long-term due to unresolved issues regarding immune-compatibility. While various solutions to these shortcomings are currently under scrutiny, the possibility to implant fully biologically compatible valve replacements remains elusive, at least for large-scale deployment. In this regard, the failure in translation of most of the designed tissue engineered heart valves (TEHVs) to a viable clinical solution has played a major role. In this review, we present a comprehensive overview of the TEHVs developed until now, and critically analyze their strengths and limitations emerging from basic research and clinical trials. Starting from these aspects, we will also discuss strategies currently under investigation to produce valve replacements endowed with a true ability to self-repair, remodel and regenerate. We will discuss these new developments not only considering the scientific/technical framework inherent to the design of novel valve prostheses, but also economical and regulatory aspects, which may be crucial for the success of these novel designs.

Cells and Materials for Cardiac Repair and Regeneration

“…Scaffolds are also functionalized with proteins of the natural extracellular matrix (ECM) to promote physiological adhesion, differentiation, migration and proliferation of the cells of interest [14,89]. For several cardiovascular applications (e.g., vessels or myocardial engineering), scaffolds should be preferentially biodegradable to allow the pre-seeded or the in vivo recruited cells to deposit their own ECM [90,91], although for specific applications such as the engineering of tissues subjected to elevated levels of cyclic strain and compression forces (e.g., the cardiac valves), the use of permanent or semi-permanent scaffolds able to maintain mechanical integrity and resistance may be an advantage [92].…”

“…To this aim, specific stress/strain curves can be generated using machines for tensile strength determination to measure the mechanical resistance to strain in comparison to the non-decellularized condition. This feature is particularly important, for example, in valve leaflets' engineering for the necessity to resist up to billion straining cycles [92,104].…”

Incorporation of Controlled Release Systems Improves the Functionality of Biodegradable 3D Printed Cardiovascular Implants

“…The heart valves should resemble the native tissue microstructure, present an optimum degradation rate, and match the mechanical properties to be able to mimic the valve leaflet function. Heart valve leaflets are composed of three interconnected layers (fibrosa, spongiosa, and ventricularis), providing the typical mechanical properties such as elasticity, and are made from valvular interstitial cells spread within collagen, elastin, and glycosaminoglycans . These properties can be resembled by the 3D printing approach being able to enforce the specific parts of the valve or precisely fabricate a realistic facsimile of the native structures similar in shape.…”