Mechanical conditioning of cell-seeded small intestine submucosa: A potential tissue-engineering strategy for tendon repair

Our long-term objective is to enhance tendon repair by delivering cells on natural biologic scaffolds to the repair site. Clinical outcomes may be improved by first preconditioning these cell-seeded constructs in bioreactors to enhance their properties at implantation and to deliver cells expressing a desired phenotype. In this work, we have investigated the effect of in vitro mechanical conditioning on small-intestine submucosa (SIS) scaffolds seeded with primary tendon cells (tenocytes). SIS scaffolds (with and without cells) were conditioned under various loading regimes over a 2-week period. In vitro cyclic loading significantly increased the biomechanical properties (e.g., stiffness) of cell-seeded SIS constructs (129.1 +/- 10.2%) from time 0. The stiffness change of cyclically loaded constructs without cells was 33.9 +/- 13.8% and of statically loaded constructs with cells was 34.0 +/- 15.2% and without cells was 33.4 +/- 10.7%. In the cell-seeded groups, our data demonstrate a direct role (e.g., cell tensioning) for cells in construct stiffening. In addition, the initial stiffness of the cell-seeded, cyclically loaded constructs was found to be a strong predictor of the change in construct stiffness. Despite the mechanical integrity of these constructs being significantly less than native tendon, our data show that structural properties can be improved with in vitro mechanical conditioning. These data provide the basis for future studies investigating in vitro conditioning (mechanical, chemical) of cell-seeded ECM scaffolds and the use of such constructs for enhancing tendon repair in vivo.