Advances in Tissue Engineering of the Heart Valves: The CorTricuspid ECM Valve

This video covers the fundamental concepts, surgical technique, and experiences related to the first totally tissue-engineered valve intended for tricuspid replacement, known as the CorTricuspid ECM valve. 

This valve exemplifies the main concept of tissue engineering, which aims to regenerate organs using biomaterials as scaffolds that enable cells to grow into new tissue. The basic principle of a successful tissue engineering approach relies on the ability to create an environment that closely resembles the native extracellular matrix (ECM), a principle known as biomimicry. This allows cells to find a conducive material to engraftment, and to grow into totally regenerated tissue. 

This can be achieved by either using a polymeric scaffold designed to recapitulate the nanofibrous structure of the extracellular matrix or by decellularizing a tissue to preserve the native histoarchitecture of the extracellular matrix along with the associated biological signals.  

The CorTricuspid valve technology utilizes the decellularization approach and is designed to be implanted and progressively colonized by the patient's own cells (mainly blood progenitor cells), which will further grow and differentiate into valvular interstitial cells and eventually form a totally regenerated valve. 

The valves are provided in the form of a tube, and pledgets made from the same materials are provided to assist with implantation. 

The reason for this tubular design relates to the idea of recapitulating the embryological principles of endocardial tube formation. 

In fact, the tubular valve is designed to be anchored to the papillary muscles, which will function as hinge points. When the ventricle contracts, the tube will fold into three leaflets, and the cells colonizing the ventricular part of the tube will progressively remodel into the native subvalvular apparatus under both biological and hemodynamic stimuli. 

The implantation began with a right atriotomy, followed by the identification of the papillary muscles. This step required careful inspection of the right ventricle (RV) cavity, as the location and anatomy of the papillary muscles are more variable than those in the left ventricle (LV). The papillary muscles were identified and marked, and then the procedure continued with leafleted excision, leaving a small rim of the native leaflet. Once the leaflets were partially excised, it became easier to follow the direction of the chorda tendineae subtending each papillary muscle. The valve was brought into the field and marked according to the annulus measurement obtained from transesophageal echocardiography (TEE), which, in this case, was 34 mm. The valve was prepared and divided into three segments. The next step involved placing sutures for the subvalvular attachment. It is important to have good purchase on the stitch placed on the papillary muscles, and considering their fragility, the authors recommend leaving a generous amount of chordal structures during valve excision to serve as handles for manipulating the muscles. The authors prefer to parachute the first two pillars, typically the posterior and septal muscles, to avoid misalignment and stitch entanglement. The third papillary muscle was then attached after the valve was lowered and tied into position. The valve was subsequently flowered open and checked for mobility. At this stage, the three corresponding pillars at the atrial site will be anchored to the annulus. The procedure was then completed with three semicontinuous running sutures to finalize the atrial annular attachment of the valve. A water test was performed, and after separation from cardiopulmonary bypass, the valve was assessed via TEE in both short and long axes. In this case, the short-axis view demonstrates the trileaflet profile of the valve with minimal regurgitation, while the long-axis view depicts the valve’s subvalvular attachment. 

At the one-month follow-up, echo findings were consistent with good valvular function. Currently, 42 implants have been performed in the pivotal trial across the U.S., including both adult and pediatric populations. 

This tissue engineering approach in valve surgery holds the promise of significant advancements in cardiac surgery. The idea of a self-populating ECM-based scaffold regenerating the tricuspid valve with the patient’s own cells has important implications in the clinical scenario. First, it is expected to reduce the instances of repeat surgery, particularly in the pediatric population, where patients tend to outgrow standard artificial prosthetic valves. Secondly, because of the lack of prosthetic material or chemical fixative, the risk of calcification or structural degeneration is theoretically reduced. Finally, considering the rapid colonization of the scaffold, which normally occurs in the first six weeks with complete formation of new endocardium, there is no need for life-long anticoagulation. The long-term results of the pivotal trial with this valve and the further development of this exciting technology are eagerly awaited. 

Acknowledgements 

The surgical implanting team, included Dr. Cristiano Spadaccio and Dr. Antonio Panza. A special thank you to Dr. Morales, Chief of Pediatric Cardiac Surgery at Cincinnati Children’s Hospital, who kindly assisted with the initial procedures, and to Dr. Matheny from CorVivo. 

Surgical and clinical images are provided with patient consent and in accordance with institutional HIPAA-compliant policies. 

Editor’s Note 

To learn more about totally tissue-engineered valves, click here to view Dr. Spadaccio’s interview with Editor-in-Chief Dr. Joel Dunning. 

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