Can We Grow Valves Inside the Heart? Perspective on Material-based In Situ Heart Valve Tissue Engineering

Abstract

In situ heart valve tissue engineering using cell-free synthetic, biodegradable scaffolds is under development as a clinically attractive approach to create living valves right inside the heart of a patient. In this approach, a valve-shaped porous scaffold “implant” is rapidly populated by endogenous cells that initiate neo-tissue formation in pace with scaffold degradation. While this may constitute a cost-effective procedure, compatible with regulatory and clinical standards worldwide, the new technology heavily relies on the development of advanced biomaterials, the processing thereof into (minimally invasive deliverable) scaffolds, and the interaction of such materials with endogenous cells and neo-tissue under hemodynamic conditions. Despite the first positive preclinical results and the initiation of a small-scale clinical trial by commercial parties, in situ tissue formation is not well understood. In addition, it remains to be determined whether the resulting neo-tissue can grow with the body and preserves functional homeostasis throughout life. More important yet, it is still unknown if and how in situ tissue formation can be controlled under conditions of genetic or acquired disease. Here, we discuss the recent advances of material-based in situ heart valve tissue engineering and highlight the most critical issues that remain before clinical application can be expected. We argue that a combination of basic science – unveiling the mechanisms of the human body to respond to the implanted biomaterial under (patho)physiological conditions – and technological advancements – relating to the development of next generation materials and the prediction of in situ tissue growth and adaptation – is essential to take the next step towards a realistic and rewarding translation of in situ heart valve tissue engineering.

Role of Modern Technologies in Tissue Engineering

“…Tissue engineering is an emerging multidisciplinary field that employs the principles of engineering, chemical science, and biological science with the basic aim of tissue regeneration (8). It is an interdisciplinary area that combines cellular behavior and methods of growing cells on a scaffold (an artificial substrate) in the presence of appropriate biochemical factors needed to develop artificial organs and tissues or regenerate damaged tissues (9)(10)(11)(12). A distinguishing characteristic of TE is the ability of the regeneration of the patient's own organs and tissues that not only are completely free of low bio-functionality and poor biocompatibility but also severe immunological rejection (13).…”

“…In some situations, biomaterials are altered to strengthen the attachment and migration of specific cell populations to replace or repair the injured tissue (28). Cardiovascular tissues like blood vessels (12,29) and heart valves (30,31) are now being engineered by scientists. To give extracorporeal assistance to patients suffering from liver failure, liver-assist systems comprising encapsulated hepatocytes have been used at a clinical level (31,32) and encapsulated pancreatic islets have been implanted in diabetic patients for the cure of diabetes (33).…”

Forming effective relationships between academia and the medical devices industry with a focus on launching a smart heart valve prosthesis for pediatric patients

“…yield functional organ growth. The concept was described in multiple scientific reports [2] and successes in the animal model were widely discussed [8][9][10]. Our added value was basing the scaffold manufacturing process on textile technology and using the advantages of the fabric architecture, which was discussed in depth elsewhere [4,7].…”

Early cost-utility analysis of tissue-engineered heart valves compared to bioprostheses in the aortic position in elderly patients

“…Tissue-engineered heart valves (TEHV) can potentially limit the disadvantages of existing heart valve substitutes [6,[9][10][11]. Lately, emphasis has shifted towards the development of in situ TEHV [10].…”