Tissue-Engineered Small-Caliber Vascular Graft Based on a Novel Biodegradable Composite Fibrin-Polylactide Scaffold

Abstract

Small-caliber vascular grafts (< or =5 mm) constructed from synthetic materials for coronary bypass or peripheral vascular repair below the knee have poor patency rates, while autologous vessels may not be available for harvesting. The present study aimed to create a completely autologous small-caliber vascular graft by utilizing a bioabsorbable, macroporous poly(L/D)lactide 96/4 [P(L/D)LA 96/4] mesh as a support scaffold system combined with an autologous fibrin cell carrier material. A novel molding device was used to integrate a P(L/D)LA 96/4 mesh in the wall of a fibrin-based vascular graft, which was seeded with arterial smooth muscle cells (SMCs)/fibroblasts and subsequently lined with endothelial cells. The mold was connected to a bioreactor circuit for dynamic mechanical conditioning of the graft over a 21-day period. Graft cell phenotype, proliferation, extracellular matrix (ECM) content, and mechanical strength were analyzed. alpha-SMA-positive SMCs and fibroblasts deposited ECM proteins into the graft wall, with a significant increase in both cell number and collagen content over 21 days. A luminal endothelial cell lining was evidenced by vWf staining, while the grafts exhibited supraphysiological burst pressure (>460 mmHg) after dynamic cultivation. The results of our study demonstrated the successful production of an autologous, biodegradable small-caliber vascular graft in vitro, with remodeling capabilities and supraphysiological mechanical properties after 21 days in culture. The approach may be suitable for a variety of clinical applications, including coronary artery and peripheral artery bypass procedures.

Artificial Niche Combining Elastomeric Substrate and Platelets Guides Vascular Differentiation of Bone Marrow Mononuclear Cells

“…In particular, plasma fibrinogen can polymerize to fibrin on biomaterial surfaces, and fibrin mediates a variety of cellular behaviors, including adhesion, proliferation, and migration. 26,44 In this study, we found that platelet-poor plasma significantly improved cell seeding efficiency (Fig. 4) and proliferation (Figs.…”

Vessel Bioengineering

“…22 As an alternative to collagen for natural ECM-based scaffolds, fibrin holds particular promise because of its ability to induce collagen and elastin synthesis and improved mechanical properties. 23 Furthermore, by combining fibrin gels with biodegradable polymeric scaffolds followed by seeding of autologous arterial-derived cells, 24 endothelialized vessels have been successfully implanted in the carotid arteries of sheep. 25 Decellularized tissue, often in the form of a xenogeneic, can serve as a naturally available scaffold.…”

The Evolution of Vascular Tissue Engineering and Current State of the Art

“…commun.]. The recent work of Jockenhoevel and colleagues combines the use of fibrin gels with biodegradable scaffolds (knitted polylactide) [Tschoeke et al, 2009]. After 21 days of dynamic conditioning, these grafts seeded with ovine vascular cells had only a burst pressure of 466 8 78 mm Hg (ID ; 5 mm), which was ; 1/3 that of the ovine carotid artery.…”