The effect of stromal cell-derived factor-1α/heparin coating of biodegradable vascular grafts on the recruitment of both endothelial and smooth muscle progenitor cells for accelerated regeneration

Abstract

Small-diameter synthetic vascular grafts have high failure rate and tissue-engineered blood vessels are limited by the scalability. Here we engineered bioactive materials for in situ vascular tissue engineering, which recruits two types of endogenous progenitor cells for the regeneration of blood vessels. Heparin was conjugated to microfibrous vascular grafts to suppress thrombogenic responses, and stromal cell-derived factor-1α (SDF-1α) was immobilized onto heparin to recruit endogenous progenitor cells. Heparin-bound SDF-1α was more stable than adsorbed SDF-1α under both static and flow conditions. Microfibrous grafts were implanted in rats by anastomosis to test the functional performance. Heparin coating improved the short-term patency, and immobilized SDF-1α further improved the long-term patency. SDF-1α effectively recruited endothelial progenitor cells (EPCs) to the luminal surface of the grafts, which differentiated into endothelial cells (ECs) and accelerated endothelialization. More interestingly, SDF-1α increased the recruitment of smooth muscle progenitor cells (SMPCs) to the grafts, and SMPCs differentiated into smooth muscle cells (SMCs) in vivo and in vitro. Consistently, SDF-1α-immobilized grafts had significantly higher elastic modulus. This work demonstrates the feasibility of simultaneously recruiting progenitor cells of ECs and SMCs for in situ blood vessel regeneration. This in situ tissue engineering approach will have broad applications in regenerative medicine.

A Cautionary Tale for Autologous Vascular Tissue Engineering: Impact of Human Demographics on the Ability of Adipose-Derived Mesenchymal Stem Cells to Recruit and Differentiate into Smooth Muscle Cells

“…[18][19][20][21][22] Providing further evidence for this phemonmenon, implanted scaffolds with low porosity 28,30,32 and even TEBVs with already intact SMC layers 24 have been shown to be repopulated with host vessel wall cells. In addition, vascular engineering methods have begun to take advantage of host recellularization by creating acellular approaches, utilizing bound growth factors or drug delivery methods, 19,23,96 or designing porous scaffolds to facilitate this cellular infiltration. 31,46,97,98 In all of these cases, establishing a mature TEBV populated by SMCs requires recruitment of host cells.…”

“…In vascular tissue engineering, this paracrine signaling appears to be an important mechanism [18][19][20][21][22] by which tissueengineered blood vessels (TEBVs) remodel. Recent studies have shown they possess a dynamic environment that is repopulated with host cells, [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] such as by the inward migration of vascular smooth muscle cells (SMCs).…”

Pharmacology of Heparin and Related Drugs

“…Bridging the gap between heparin-treated prostheses and tissue engineering are developments such as SDF1a/heparin-coated vascular grafts for the recruitment of progenitor cells (Yu et al, 2012).…”

Multifunctional biomaterial coatings: synthetic challenges and biological activity

“…Recruitment of endothelial progenitor cells was enhanced through the cumulative release of SDF-1. In addition, Yu et al (2012) showed increased migration and differentiation of smooth muscle progenitor cells. The growth factor BMP-2 can bind to several polysaccharides (Tables 3 and 4).…”

“…The strong interaction of heparin and SDF-1 was also applied for the coating of cardiovascular devices. Yu et al (2012) and Lee et al (2013b) described the increased stability of the chemokine SDF-1 when present in a coacervate with heparin. Recruitment of endothelial progenitor cells was enhanced through the cumulative release of SDF-1.…”