Tendon tissue engineering using cell-seeded umbilical veins cultured in a mechanical stimulator

The goal of this study was to investigate the effect of cyclic mechanical stimulation on mesenchymal stem cells (MSCs) seeded within human umbilical veins (HUVs), and to determine the potential of the engineered constructs to function as tendon tissue replacement models. Decellularized HUVs were seeded with MSCs embedded in type I collagen hydrogel. A mechanical stimulator for tissue engineering applications was specifically designed to cyclically tension the constructs for durations up to 2 weeks, where controls were left untensioned. This HUV model system seeded with a cellular collagen gel, coupled with mechanical stimulation, resulted in improved mechanical properties compared to other tendon tissue engineered constructs composed of cellular collagen gel alone, without any additional supporting scaffold. After 2 weeks of culture an increase in cell number was measured for both tensioned and untensioned constructs; however, the increase was at least eightfold higher for stimulated samples. Microscopically, cyclically tensioned samples showed parallel orientation of collagen fibers and spindle-shaped cell nuclei mimicking the morphology of native tendons. Moreover, mechanostimulation resulted in significantly stronger (156%) and stiffer (109%) constructs compared to untensioned samples. This engineered tendon model had an ultimate tensile strength value only one order of magnitude lower than human tendons and strain values in the range of human tendons. The results documented are promising and can be further improved by optimizing potentially critical culture parameters such as seeding density, loading regimes, and mechanostimulation durations.