Clinical Application for Tissue Engineering Focused on Materials

Abstract

Cardiovascular-related medical conditions remain a significant cause of death worldwide despite the advent of tissue engineering research more than half a century ago. Although autologous tissue is still the preferred treatment, donor tissue is limited, and there remains a need for tissue-engineered vascular grafts (TEVGs). The production of extensive vascular tissue (>1 cm3) in vitro meets the clinical needs of tissue grafts and biological research applications. The use of TEVGs in human patients remains limited due to issues related to thrombogenesis and stenosis. In addition to the advancement of simple manufacturing methods, the shift of attention to the combination of synthetic polymers and bio-derived materials and cell sources has enabled synergistic combinations of vascular tissue development. This review details the selection of biomaterials, cell sources and relevant clinical trials related to large diameter vascular grafts. Finally, we will discuss the remaining challenges in the tissue engineering field resulting from complex requirements by covering both basic and clinical research from the perspective of material design.

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, the development of commercially available off-the-shelf TEVG is highly relevant to the current demands of cardiac surgery, neurosurgery, and microsurgery and would significantly address a growing need in the increase in vascular reconstruction procedures, none of the TEVG prototypes has passed through the pre-clinical trials hitherto. Among the most frequent complications of TEVG implantation are thrombosis, aneurysms, neointimal hyperplasia, calcification, atherosclerosis, and infection [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ]. Previously, our group reported an efficient approach for increasing haemocompatibility and thrombosis prevention by immobilising an anticoagulant heparin and a vasodilator/antiplatelet drug, iloprost, to the luminal surface of PCL-based TEVGs [ 25 ].…”

“…Therefore, the advantages of our PCL Ilo/CAD TEVGs included controlled replacement of the biodegradable polymer by de novo vascular tissue and freedom from a number of main complications accompanying the TEVG implantation (thrombosis, calcification, atherosclerosis, and infection). Although PCL Ilo/CAD TEVGs did not have a clear basement membrane, it did not hinder endothelialisation, a mandatory pre-requisite for haemocompatibility and thromboresistance [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ], and a CD31- and vWF-positive EC monolayer has been observed. The most significant drawback was the lack of the hierarchical arterial medial structure which is recognisable by elastic fibers and contractile VSMCs that form lamellar units in the elastic arteries, such as the carotid artery.…”

“…Therefore, TEVGs still represent an unmet clinical need, despite more than two decades of development [ 1 , 2 ]. 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 ]).…”

Design of Functional RGD Peptide-Based Biomaterials for Tissue Engineering

“…Therefore, small-diameter (6 mm inner diameter) vascular grafts may serve as a basis for long-term treatment [ 61 ]. The field of vascular TE is a relatively new one that has undergone replacement with bio-functionalities [ 62 ]. RGD-modified peptide grafts exhibit the ability to inhibit platelet adhesion, resulting in enhanced cellular infiltration, endothelialization, and ECM formation [ 61 , 63 ].…”

Advances in Cardiac Tissue Engineering

“…Transplanted MSC sheets using cells obtained from bone tissue, adipose tissue, and menstrual blood also showed some myocardial formation and dramatic paracrine effects that contribute to angiogenesis, cardioprotection, improved LV function, and myocardial repair ( Figure 1 ). MSCs can be applied not only in heart sheets but also in regenerative blood vessels, for the cells contribute to the relaxation of the immune response of tissue-engineered vascular grafts (TEVGs) [ 19 ]. These applications confirm the safety of MSC and its partial mechanism of action.…”