Construction and Evaluation of a Bio-Engineered Pump to Enable Subpulmonary Support of the Fontan Circulation: A Proof-of-Concept Study

Abstract

Christopher r. Broda ,* p. alex smith , † Yaxin Wang ‡; hamsini sriraman, § peter s. oWuor, ¶ luiz C. sampaio ,∥ iki adaChi,# and doris a. taYlor, **, † † Our objective was to create a bio-engineered pump (BEP) for subpulmonary Fontan circulation support capable of luminal endothelialization and producing a 2-6 mmHg pressure gradient across the device without flow obstruction. To accomplish this, porcine urinary bladder submucosa was decellularized to produce a urinary bladder matrix (UBM) which produced acellular sheets of UBM. The UBM was cultured with human umbilical vein endothelial cells producing a nearly confluent monolayer of cells with the maintenance of typical histologic features demonstrating UBM to be a suitable substrate for endothelial cells. A lamination process created bilayer UBM sheets which were formed into biologic reservoirs. BEPs were constructed by securing the biologic reservoir between inlet and outlet valves and compressed with a polyurethane balloon. BEP function was evaluated in a simple flow loop representative of a modified subpulmonary Fontan circulation. A BEP with a 92-mL biologic reservoir operating at 60 cycles per minute produced pulsatile downstream flows without flow obstruction and generated a favorable pressure gradient across the device, maintaining upstream pressure of 6 mm Hg and producing downstream pressure of 13 mm Hg. The BEP represents potential long-term assistance for the Fontan circulation to relieve venous hypertension, provide pulsatile pulmonary blood flow and maintain cardiac preload.

Recapitulation of single ventricle haemodynamics and associated interplay with breathing mechanics using clinically validated multimodal simulators

“…Due to its high anatomical fidelity and currently unmatched re-creation of biomechanical interactions of respiration and blood flow, our system may constitute a valuable tool for the translation of Fontan support strategies (figure 8). To demonstrate the usability of this biomimetic Fontan simulator as a test platform for device evaluation, we implanted a one-way valve in the benchtop simulator to support Fontan haemodynamics as previously suggested in the literature 7,32,[49][50][51] . To characterize the risks associated with implanted devices, a detailed haemodynamic assessment of blood flow and its interaction with the device is essential in addition to organ level flow evaluations 35,52,53 .…”

“…In figure 8c-d we demonstrate the usability of the biomimetic Fontan simulator for device testing by embedding a unidirectional valve (here we use a St. Jude now Abbott mechanical valve as an exemplary device) into the location of the Fontan shunt. Unidirectional valves in this position have been suggested as standalone strategies to improve univentricular haemodynamics 32,47 , and in combination with compression devices or and skeletal muscle pumps 37,48,49 . In figure 8d, we show the resulting IVC flow after valve implantation in the biomimetic benchtop simulator.…”