Vascular reconstruction: A major challenge in developing a functional whole solid organ graft from decellularized organs

Abstract Bioengineering a functional organ holds great potential to overcome the current gap between the organ need and shortage of available organs. Whole organ decellularization allows the removal of cells from large-scale organs, leaving behind extracellular matrices containing different growth factors, structural proteins, and a vascular network with a bare surface. Successful application of decellularized tissues as transplantable organs is hampered by the inability to completely reline the vasculature by endothelial cells (ECs), leading to blood coagulation, loss of vascular patency, and subsequent death of reseeded cells. Therefore, an intact, continuous layer of endothelium is essential to maintain proper functioning of the vascular system, which includes the transfer of nutrients to surrounding tissues and protecting other types of cells from shear stress. Here, we aimed to summarize the available cell sources that can be used for reendothelialization in addition to different trials performed by researchers to reconstruct vascularization of decellularized solid organs. Additionally, different techniques for enhancing reendothelialization and the methods used for evaluating reendothelialization efficiency along with the future prospective applications of this field are discussed. Statement of significance Despite the great progress in whole organ decellularization, reconstruction of vasculature within the engineered constructs is still a major roadblock. Reconstructed endothelium acts as a multifunctional barrier of vessels, which can reduce thrombosis and help delivering of oxygen and nutrients throughout the whole organ. Successful reendothelialization can be achieved through reseeding of appropriate cell types on the naked vasculature with or without modification of its surface. Here, we present the current research milestones that so far established to reconstruct the vascular network in addition to the methods used for evaluating the efficiency of reendotheilization. Thus, this review is quite significant and will aid the researchers to know where we stand toward biofabricating a transplantable organ from decellularizd extracellular matrix.