Tissue Engineering at the Blood‐Contacting Surface: A Review of Challenges and Strategies in Vascular Graft Development

Abstract

Tissue engineered vascular grafts (TEVGs) are beginning to achieve clinical success and hold promise as a source of grafting material when donor grafts are unsuitable or unavailable. Significant technological advances have generated small-diameter TEVGs that are mechanically stable and promote functional remodeling by regenerating host cells. However, developing a biocompatible blood-contacting surface remains a major challenge. The TEVG luminal surface must avoid negative inflammatory responses and thrombogenesis immediately upon implantation and promote endothelialization. The surface has therefore become a primary focus for research and development efforts. The current state of TEVGs is herein reviewed with an emphasis on the blood-contacting surface. General vascular physiology and developmental challenges and strategies are briefly described, followed by an overview of the materials currently employed in TEVGs. The use of biodegradable materials and stem cells requires careful control of graft composition, degradation behavior, and cell recruitment ability to ensure that a physiologically relevant vessel structure is ultimately achieved. The establishment of a stable monolayer of endothelial cells and the quiescence of smooth muscle cells are critical to the maintenance of patency. Several strategies to modify blood-contacting surfaces to resist thrombosis and control cellular recruitment are reviewed, including coatings of biomimetic peptides and heparin.

Strategies in cell‐free tissue‐engineered vascular grafts

“…But one major obstacle of synthetic materials is the lack of cell communication signals and integrin-binding sites, which might reduce cell attachment and infiltration (Radke et al, 2018). In contrast, natural materials always suffer from insufficient strength and are confronted with aneurysm and rupture, but can process better biocompatibility since they can be remodeled by host cells and the degradation products can be absorbed or metabolized and excreted by the human body.…”

“…For the clinical appropriate grafts longer than 10 cm, the unique way to achieve completely endothelialization is to recruit ECs and EPCs from circulation. These natural topographical features may provide an increased cellular attachment as well as alignment in the direction of blood flow (Radke et al, 2018). Recently, there are no efficient methods to increase ECs and EPCs number and to accelerate their proliferation.…”

“…In addition, the RGD peptide can detach from the graft base membrane after binding with cells via integrin receptors due to the low molecular weight(Radke et al, 2018). In addition, the RGD peptide can detach from the graft base membrane after binding with cells via integrin receptors due to the low molecular weight(Radke et al, 2018).…”

Target regulation of both VECs and VSMCs by dual‐loading miRNA‐126 and miRNA‐145 in the bilayered electrospun membrane for small‐diameter vascular regeneration

“…Vascular transplantation is one of the effective methods to deal with high incidence of blood vessel diseases . However, the clinical utility of small‐diameter (<6 mm) vascular grafts is still a thorny challenge because of thrombosis or intimal hyperplasia .…”

“…Electrospinning is a unique technique to prepare nano‐ or micro‐structured membranes, and has been widely used to fabricate vascular grafts . Electrospun fibrous membranes can also efficiently load bioactive agents and drugs for regulation of cellular physiological functions .…”