Biofabrication in Congenital Cardiac Surgery: A Plea from the Operating Theatre, Promise from Science

Abstract

Despite significant advances in numerous fields of biofabrication, clinical application of biomaterials combined with bioactive molecules and/or cells largely remains a promise in an individualized patient settings. Three-dimensional (3D) printing and bioprinting evolved as promising techniques used for tissue-engineering, so that several kinds of tissue can now be printed in layers or as defined structures for replacement and/or reconstruction in regenerative medicine and surgery. Besides technological, practical, ethical and legal challenges to solve, there is also a gap between the research labs and the patients' bedside. Congenital and pediatric cardiac surgery mostly deal with reconstructive patient-scenarios when defects are closed, various segments of the heart are connected, valves are implanted. Currently available biomaterials lack the potential of growth and conduits, valves derange over time surrendering patients to reoperations. Availability of viable, growing biomaterials could cancel reoperations that could entail significant public health benefit and improved quality-of-life. Congenital cardiac surgery is uniquely suited for closing the gap in translational research, rapid application of new techniques, and collaboration between interdisciplinary teams. This article provides a succinct review of the state-of-the art clinical practice and biofabrication strategies used in congenital and pediatric cardiac surgery, and highlights the need and avenues for translational research and collaboration.

Keywords: 3D bioprinting; bioactive molecules; biofabrication; biomaterials; congenital cardiac surgery; congenital heart disease; reconstructive surgery; stem cells; tissue engineering; translational research.

Figure 1

Biomaterials used in congenital and pediatric cardiac surgery. Examples shown herein for illustration and are not all-inclusive. Composite category defines biomaterials that conjoin natural biomaterials with synthetically manufactured scaffolds. Abbreviations: PTFE: polytetrafluoroethylene, SIS-ECM: small intestine mucosa extracellular matrix.

Figure 2

Intraoperative endoscopic images of ventricular septal defect (VSD) patch closure during repair of tetralogy of Fallot. (A) The septal leaflet (SL) of the tricuspid valve (TV) is detached and retracted and the VSD is assessed. The defect has fibrous ridges. (B) Left ventricle to aorta tunnel is completed by autologous pericardium patch, thus the VSD is closed (transventricular view). (C) The detached tricuspid leaflets are reattached to annulus and commissuroplasty is performed. Abbreviations: AL: anterior leaflet of the tricuspid valve; CS: coronary sinus; PI: posteroinferior leaflet of the tricuspid valve; RA: right atrium; RV: right ventricle; SL: septal leaflet of the tricuspid valve; TV: tricuspid valve.

Figure 3

(A) Intraoperative representation of pulmonary atresia with absent intrapericardial pulmonary arteries. Ascending aorta (Ao) is the only outlet from the heart. Patent arterial duct (PDA) perfuses the left pulmonary artery (not visible). Left atrial appendage is retracted to expose the left coronary artery system (LAD: left anterior descending and Cx: circumflex branches). (B) 3D-printed blood-volume model of pulmonary atresia, VSD and major aortopulmonary collaterals arteries (MAPCAs); right aortic arch. The right ventricle outflow tract is missing and the native pulmonary arteries are hypoplastic. Majority of the pulmonary circulation depends on the MAPCAs (*). Surgical planning is grossly supported by a detailed 3D-printed models. In both cases, the paramount surgical task involves reconstruction of the intrapericardial pulmonary arteries and connecting them to the right ventricle via a preferably valved and growing conduit. Abbreviations: AO: ascending aorta; Cx: circumflex branch of the left coronary artery; IA: innominate artery; IV: innominate vein; LAA: left atrial appendage; LAD: left anterior descending branch of the left coronary artery; LCCA: left common carotid artery; LPA: left pulmonary artery; LV: left ventricle; PDA: patent arterial duct; RA: right atrium; RCCA: right common carotid artery; RPA: right pulmonary artery; RV: right ventricle; VSD: ventricular septal defect. Trachea is shown in blue.

Figure 4

Various biomaterials utilized during complex neonatal cardiac reconstructive surgeries. Images taken from the intraoperative video recording. (A) Right ventricle-to-pulmonary artery (RV-PA) connection with valved bovine conduit. (B) RV-PA connection with ringed expanded polytetrafluoroethylene (ePTFE) conduit; the pulmonary trunk serves as the systemic outlet of the heart and it is connected to the aortic arch, ascending and descending aorta in a complex anastomosis augmented with autologous pericardium patch. During the arch repair, selective cerebral perfusion is performed through the ePTFE tube (*) connected to the innominate artery. Abbreviations: Ao: ascending aorta; PT: pulmonary trunk; RA: right atrium; RV: right ventricle.

Figure 5

(A) Pulmonary allograft at implantation. (B) Intraoperative image of severely calcified allograft conduit. Abbreviations: AL: insertion point of the arterial ligament; LPA: left pulmonary artery; PT: pulmonary trunk; RPA: right pulmonary artery; RVOT: right ventricle outflow tract.

Figure 6

Concept schematic of bioprinting a patient-specific personalized cardiac tissue [112].

Figure 7

Process flow of biofabrication strategies for congenital cardiac surgery.

Figure 8

New methods and applications centered around the patient will revolutionize regenerative surgery.