A step closer to elastogenesis on demand; Inducing mature elastic fibre deposition in a natural biomaterial scaffold

Abstract

Elastic fibres play a key role in bodily functions where fatigue resistance and elastic recovery are necessary while regulating phenotype, proliferation and migration in cells. While in vivo elastic fibres are created at a late foetal stage, a major obstacle in the development of engineered tissue is that human vascular smooth muscle cells (hVSMCs), one of the principal elastogenic cells, are unable to spontaneously promote elastogenesis in vitro. Therefore, the overall aim of this study was to activate elastogenesis in vitro by hVSMCs seeded in fibrin, collagen, glycosaminoglycan (FCG) scaffolds, following the addition of recombinant human tropoelastin. This combination of scaffold, tropoelastin and cells induced the deposition of elastin and formation of lamellar maturing elastic fibres, similar to those found in skin, blood vessels and heart valves. Furthermore, higher numbers of maturing branched elastic fibres were synthesised when a higher cell density was used and by drop-loading tropoelastin onto cell-seeded FCG scaffolds prior to adding growth medium. The addition of tropoelastin showed no effect on cell proliferation or mechanical properties of the scaffold which remained dimensionally stable throughout. With these results, we have established a natural biomaterial scaffold that can undergo controlled elastogenesis on demand, suitable for tissue engineering applications.