The Effect of Gradations in Mineral Content, Matrix Alignment, and Applied Strain on Human Mesenchymal Stem Cell Morphology within Collagen Biomaterials

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The tendon-bone junction is a unique, mechanically dynamic, structurally graded anatomical zone, which transmits tensile loads between tendon and bone. Current surgical repair techniques rely on mechanical fixation and can result in high re-failure rates. A new class of collagen biomaterial that contains discrete mineralized and structurally aligned regions linked by a continuous interface to mimic the graded osteotendinous insertion has been recently described. Here the combined influence of graded biomaterial environment and increasing levels of applied strain (0%–20%) on mesenchymal stem cell (MSC) orientation and alignment have been reported. Inosteotendinousscaffolds, which contain opposing gradients of mineral content and structural alignment characteristic of the native osteotendinous interface, MSC nuclear, and actin alignment is initially dictated by the local pore architecture, while applied tensile strain enhances cell alignment in the direction of strain. Comparatively, inlayeredscaffolds that do not contain any structural alignment cues, MSCs are randomly oriented in the unstrained condition, then become oriented in a direction perpendicular to applied strain. These findings provide an initial understanding of how scaffold architecture can provide significant, potentially competitive, feedback influencing MSC orientation under applied strain, and form the basis for future tissue engineering efforts to regenerate the osteotendinous enthesis.

The effect of transitions is reported in pore anisotropy and mineral content across 3D collagen scaffolds on mesenchymal stem cell (MSC) alignment in response to tensile strain. MSCs align consistently in the direction of local pore architecture, though in response to strain cells in isotropic scaffolds orient perpendicular to strain. Scaffold pore architecture provides significant structural feedback influencing MSC orientation under strain.

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