Positive changes in bone marrow-derived cells in response to culture on an aligned bioscaffold

Previous studies have shown that cultured cells align with the local topography of their substrate following a concept called "contact guidance.'' Additionally, if the topography is highly aligned, the cells produce newly synthesized matrix that is also aligned. The objective of this study was to elucidate the positive effect of cell seeding on an elongated porcine small intestinal submucosa (SIS), which has been shown to improve ligament and tendon healing, by measuring the cellular response as a result of the changes in alignment. Because elongation is known to align the fibers of SIS through recruitment along the direction of elongation, we hypothesized that rabbit bone marrow-derived cells (BMDCs) seeded on SIS with improved fiber alignment would increase the expression and production of collagen following the concept of contact guidance. Using the small-angle light-scattering technique, it was found that a 15% elongation together with BMDC seeding on SIS (elongated, seeded group) improved its alignment of collagen fibers up to 16 times more than no elongation and no BMDC seeding (non-elongated, non-seeded group). Furthermore, BMDCs were also aligned along the direction of elongation and showed 200% greater collagen type I gene expression in the elongated, seeded group than in Petri dish controls. More importantly, the production of collagen was also 24% greater. The results of this study demonstrate that alignment of a bioscaffold can result in positive changes in cellular response, making the bioscaffold more attractive for functional tissue engineering to potentially enhance healing of ligaments and tendons.