(145c) Tendon Tissue Engineering Using Mechanical Stimulation of Mesenchymal Stem Cells

Tendon injuries require prolonged durations of rest and immobility. When surgery becomes inevitable four material options are available: autografts, allografts, xenografts, and prosthetic devices. Autografts have limited availability, and result in a double incision, while allografts and xenografts often result in an immune response. Prosthetic devices, on the other hand, are a temporary solution since their integrity is compromised with increased usage. To augment the limitations in the current treatments of tendon defects and injuries, researchers have attempted to engineer tendon-like tissue in-vitro that is biocompatible and possesses comparable mechanical properties to the innate tissue.

The goal of this study was to investigate the effect of cyclic mechanical stimulation on mesenchymal stem cells (MSC) seeded within human umbilical veins (HUVs), and to determine the potential of the engineered constructs to function as tendon tissue replacement models. Decelulerized HUVs were seeded with MSC's and cultured for periods of 1 and 2 weeks. A novel bioreactor was designed to house and mechanically stimulate the constructs where controls were left un-tensioned. Mechanical stimulation resulted in 8 fold higher proliferation rates and significantly stronger (156%) and stiffer (109%) constructs compared to un-tensioned samples. Microscopically, cyclically tensioned samples showed parallel orientation of collagen fibers and spindle-shaped cell nuclei mimicking the morphology of native tendons. This study further investigated the effect of different daily loading durations on constructs. 1 hour of mechano-stimulation per day resulted in higher proliferation rates and stronger constructs than static cultures. However, extended 24 hour cyclic stretching resulted in cell lyses and significant weakening of constructs.