Elastin and viscoelasticity in cell-seeded collagen constructs cultured in vitro: Implications for tissue-engineered blood vessels.

摘要

The development of an exclusively biological tissue engineered (TE) vascular prosthesis will depend on many factors, but few are as critical as the requirement for appropriate mechanical properties. Structural integrity, elasticity, and durability are all crucial for long-term success in the hemodynamic environment. Cell-seeded collagen constructs have provided an attractive model to study vascular development and cell function, but they exhibit inferior strength and elastic recoil. Elastin was identified as an extracellular matrix (ECM) protein that might improve the mechanical properties, and experiments were performed to evaluate different approaches by which elastin could be incorporated into the grafts. Fragments of exogenous elastins were unable to be remodeled into a functional matrix. Although they altered the geometries of the constructs little change was observed in the mechanical properties. When intact elastin scaffolds were combined with collagen constructs to form hybrid grafts, increased mechanical strengths and improved viscoelastic properties were seen. Similar effects were observed when cell-seeded collagen gels were combined acellular collagen support sleeves to form construct sleeve hybrid grafts. De novo elastin production through genetic engineering was also investigated. Expression of the mRNA transcripts was detected, but insufficient protein was produced to assess the resulting effects on mechanical performance. Methods for viscoelastic characterization were developed and a number of approaches to improve the mechanical behaviors of constructs were identified. This work brings the collagen-based vascular graft closer to implantation.