Tissue-Engineered Vascular Grafts for Use in the Treatment of Congenital Heart Disease: From the Bench to the Clinic and Back Again

Abstract

Since the first tissue-engineered vascular graft (TEVG) was implanted in a child over a decade ago, growth in the field of vascular tissue engineering has been driven by clinical demand for improved vascular prostheses with performance and durability similar to an autologous blood vessel. Great strides were made in pediatric congenital heart surgery using the classical tissue engineering paradigm, and cell seeding of scaffolds in vitro remained the cornerstone of neotissue formation. Our second-generation bone marrow cell-seeded TEVG diverged from tissue engineering dogma with a design that induces the recipient to regenerate vascular tissue in situ. New insights suggest that neovessel development is guided by cell signals derived from both seeded cells and host inflammatory cells that infiltrate the graft. The identification of these signals and the regulatory interactions that influence cell migration, phenotype and extracellular matrix deposition during TEVG remodeling are yielding a next-generation TEVG engineered to guide neotissue regeneration without the use of seeded cells. These developments represent steady progress towards our goal of an off-the-shelf tissue-engineered vascular conduit for pediatric congenital heart surgery.

Fibroblast engraftment in the decellularized mouse lung occurs via a β1-integrin-dependent, FAK-dependent pathway that is mediated by ERK and opposed by AKT

“…bioengineering; decellularized lung; fibroblast EX VIVO ENGINEERING STRATEGIES have emerged as important approaches for the study of tissue regeneration in a wide variety of organs including the vasculature (20), genitourinary system (7), spinal cord (34), and kidney (28). Until recently, similar advances in pulmonary biology had been limited by the complex three-dimensional structure and functional anatomy of the intact lung.…”

Comparison of a Closed System to a Standard Open Technique for Preparing Tissue-Engineered Vascular Grafts

“…1,2 This has significant implications for children, particularly those with congenital heart disease. [3][4][5] Before the potential of the TEVG can be fully realized, simpler, safer, and more rapid methods for assembling TEVGs (i.e., cell isolation, cell seeding, and incubation) need to be developed. Development of a closed disposable seeding system would overcome a critical barrier and would make this technology available to many more patients.…”

“…The BM-MNCs are then seeded onto the scaffold using vacuum seeding (4, 4a). The effluent is then transferred to the seeding chamber thus bathing the seeded scaffold (5). At that time, the tubing is heat sealed and the TEVG is placed in the incubation chamber for 2 h, at which point it is ready for surgical implantation.…”

“…[3][4][5] To construct the TEVG, autologous bone marrow-derived mononuclear cells (BM-MNCs) are isolated and seeded onto (glycolic acid) fibers knitted into a tube and coated with a 50:50 copolymer of e-caprolactone and L-lactic acid.…”

Regenerative medicine: Current therapies and future directions

“…These polymers can be engineered to be biodegradable, enabling gradual replacement of the scaffold by the cells seeded in the graft as well as by host cells (39). For example, this approach was used to fabricate tissue-engineered vascular grafts (TEVGs), which have entered clinical trials, for treating congenital heart defects in both pediatric and adult patients (40) (Fig. 1 A and B).…”