Coatings in Decellularized Vascular Scaffolds for the Establishment of a Functional Endothelium: A Scoping Review of Vascular Graft Refinement

Abstract

Developments in tissue engineering techniques have allowed for the creation of biocompatible, non-immunogenic alternative vascular grafts through the decellularization of existing tissues. With an ever-growing number of patients requiring life-saving vascular bypass grafting surgeries, the production of functional small diameter decellularized vascular scaffolds has never been more important. However, current implementations of small diameter decellularized vascular grafts face numerous clinical challenges attributed to premature graft failure as a consequence of common failure mechanisms such as acute thrombogenesis and intimal hyperplasia resulting from insufficient endothelial coverage on the graft lumen. This review summarizes some of the surface modifying coating agents currently used to improve the re-endothelialization efficiency and endothelial cell persistence in decellularized vascular scaffolds that could be applied in producing a better patency small diameter vascular graft. A comprehensive search yielding 192 publications was conducted in the PubMed, Scopus, Web of Science, and Ovid electronic databases. Careful screening and removal of unrelated publications and duplicate entries resulted in a total of 16 publications, which were discussed in this review. Selected publications demonstrate that the utilization of surface coating agents can induce endothelial cell adhesion, migration, and proliferation therefore leads to increased re-endothelialization efficiency. Unfortunately, the large variance in methodologies complicates comparison of coating effects between studies. Thus far, coating decellularized tissue gave encouraging results. These developments in re-endothelialization could be incorporated in the fabrication of functional, off-the-shelf alternative small diameter vascular scaffolds.

Personalized tissue-engineered arteries as vascular graft transplants: A safety study in sheep

“…The length and diameter of the grafts were chosen to fit the sheep carotid animal model, which is in the range of coronary arteries in human [ 8 ]. Previous limited performance of decellularized grafts have been suggested to be due to lack of cellularity and exposure of the collagen surface to blood [ 10 , 11 , 32 ]. In addition to in vitro recellularization, discussed above, immobilization of modified peptides to the luminal side of small diameter long bypass arteries for improved in vivo endothelialization has been shown efficient for patency in a short-term animal study [ 24 ].…”

From waste to wealth: Repurposing slaughterhouse waste for xenotransplantation

“…The most common antigen removal methodology currently used for clinical applications relies on chemically cross-linking the proteins within xenogeneic acellular tissues with sterilants like glutaraldehyde and genipin (Cissell et al, 2014;Heng et al, 2021). Surface coating approaches are intended to make the xenogeneic proteins unrecognizable to a human patient's immune system and reduce immunogenicity (Cissell et al, 2014;Wang et al, 2016a) while supporting recellularization (Yao et al, 2020;Heng et al, 2021), as well as the structural and rheological properties of biomaterials (Wang et al, 2019b).…”

“…Nevertheless, there are individual and inherent limitations to the treatments geared toward addressing immunological barriers associated with slaughterhouse waste. As previously mentioned, the decellularization process is incapable of generating scaffolds entirely devoid of antigens, and there is also evidence that coating treatments do not entirely mask antigens (Cissell et al, 2014;Heng et al, 2021). Therefore, combining an initial antigenic removal process like detergent-based treatments with chemical cross-linking can improve the longevity of xenogeneic grafts.…”

Strategies to counteract adverse remodeling of vascular graft: A 3D view of current graft innovations

“…Hybrid graft materials composed of both biological polymers and synthetic polymers further leveraged the benefits offered by both materials for the mechanics and biological recognition of a graft. For further information, a number of reviews have provided historical views and in-depth analyses of graft fabrication techniques and graft polymers (Hiob et al, 2017;Pagel and Beck-Sickinger, 2017;Song et al, 2018;Chandra and Atala, 2019;Gentile et al, 2020;Niklason and Lawson, 2020;Syedain et al, 2020;Yuan et al, 2020;Gupta and Mandal, 2021;Heng et al, 2021;Zhang et al, 2021). By and large, a long-term, dynamic, mechanistic view is taken into the design parameters and optimizations for vascular grafts, while continuous advancements in fabrication techniques and materials allow diverse choices and better controls over design parameters.…”

“…Hybrid graft materials composed of both biological polymers and synthetic polymers further leveraged the benefits offered by both materials for the mechanics and biological recognition of a graft. For further information, a number of reviews have provided historical views and in-depth analyses of graft fabrication techniques and graft polymers ( Hiob et al, 2017 ; Pagel and Beck-Sickinger, 2017 ; Song et al, 2018 ; Chandra and Atala, 2019 ; Gentile et al, 2020 ; Niklason and Lawson, 2020 ; Syedain et al, 2020 ; Yuan et al, 2020 ; Gupta and Mandal, 2021 ; Heng et al, 2021 ; Zhang et al, 2021 ).…”