The Real Need for Regenerative Medicine in the Future of Congenital Heart Disease Treatment

Abstract

Bioabsorbable materials made from polymeric compounds have been used in many fields of regenerative medicine to promote tissue regeneration. These materials replace autologous tissue and, due to their growth potential, make excellent substitutes for cardiovascular applications in the treatment of congenital heart disease. However, there remains a sizable gap between their theoretical advantages and actual clinical application within pediatric cardiovascular surgery. This review will focus on four areas of regenerative medicine in which bioabsorbable materials have the potential to alleviate the burden where current treatment options have been unable to within the field of pediatric cardiovascular surgery. These four areas include tissue-engineered pulmonary valves, tissue-engineered patches, regenerative medicine options for treatment of pulmonary vein stenosis and tissue-engineered vascular grafts. We will discuss the research and development of biocompatible materials reported to date, the evaluation of materials in vitro, and the results of studies that have progressed to clinical trials.

Heparin-Eluting Tissue-Engineered Bioabsorbable Vascular Grafts

“…For example, the tensile strength test alone is not sufficient to ensure that the graft will not cause an aneurysm in an arterial environment. Thus, beating tests simulating arterial pressure [68], and evaluation of heparin release using the toluidine blue method must be performed [27,28]. In vitro evaluations of biocompatibility, such as platelet deposition on the luminal surface of the graft and the LDH assay [26], are necessary.…”

In VitroAnalysis of the Cytocompatibility of a Novel Porcine Aortic Patch for Vascular Reconstruction

“…Therefore, the use of autogenous grafts is not always available, thus creating a need for suitable in vivo 36: 63-75 (2022) alternatives. Alloplastic grafts, such as those made from PET or PTFE may come with an "off the shelf" availability and with variable sizes and diameters, but are also associated with higher infection risks and graft compliance mismatches, along with resulting thrombotic occlusions or intimal hyperplasia (21)(22)(23)(24). Furthermore, as they are made from synthetic materials, they lack bioactivity and are therefore limited in their ability of sufficient tissue integration, associated with possible long-term complications.…”

“…By additionally coating the inside of the graft with different glycosaminoglycans or proteins, like heparin, the patency rate can be significantly improved, so that these grafts are classified as a therapy option equivalent to autologous veins in selected indications (17,19,20). At the same time, synthetic grafts in particular for the replacement of smalllumen vessels (<6 mm) have a higher risk of thrombotic occlusions or intimal hyperplasia due to bad graft compliance mismatch, which results in poor long-term opening rates (21)(22)(23)(24). Furthermore, synthetic vascular graft materials are still associated with a higher risk of infection in the graft area (21,22).…”

“…At the same time, synthetic grafts in particular for the replacement of smalllumen vessels (<6 mm) have a higher risk of thrombotic occlusions or intimal hyperplasia due to bad graft compliance mismatch, which results in poor long-term opening rates (21)(22)(23)(24). Furthermore, synthetic vascular graft materials are still associated with a higher risk of infection in the graft area (21,22). Additionally, complications can occur due to the expansion of the grafts over time, as well as due to the mostly inadequate tissue integration of the alloplastic vessels (15).…”

Controlled and Synchronised Vascular Regeneration upon the Implantation of Iloprost- and Cationic Amphiphilic Drugs-Conjugated Tissue-Engineered Vascular Grafts into the Ovine Carotid Artery: A Proteomics-Empowered Study

“…Albeit, a number of natural and synthetic polymers, as well as their combinations, possess high biocompatibility and elasticity, drawbacks limiting the clinical translation of existing TEVGs still include insufficient haemocompatibility, biomechanical incompetence, neointimal hyperplasia, atherosclerosis, and calcification [ 5 , 6 , 7 , 8 ]. Together, these shortcomings invalidate the advantages of TEVGs, i.e., complete replacement with the regenerating vascular tissue that ensures the adaptation to body growth (particularly important in pediatric surgery [ 9 , 10 ]) and no need to harvest autologous blood vessels from other sites (beneficial for the bypass surgery [ 11 , 12 ]). In a TEVG implantation setting, vascular regeneration is provided by a biosimilar structure of the electrospun scaffold (micro- to nanoscale fiber networks which form multiple interconnected pores), rapid recruitment and proliferation of progenitor cells and their vascular differentiation guided by shear stress, cyclic pressure, and circulating growth factors [ 13 , 14 , 15 ].…”