TY - JOUR
T1 - The Effect of Gradations in Mineral Content, Matrix Alignment, and Applied Strain on Human Mesenchymal Stem Cell Morphology within Collagen Biomaterials
AU - Mozdzen, Laura C.
AU - Thorpe, Stephen D.
AU - Screen, Hazel R.C.
AU - Harley, Brendan A.C.
N1 - Funding Information:
The authors would like to thank Dr. Knight (QMUL) for providing human mesenchymal stem cells for this work, and would also like to acknowledge Dr. Chavaunne Thorpe and Dr. Dharmesh Patel for their guidance. Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award No. R21 AR063331. L.C.M. was in part funded via National Science Foundation Grant 0965918 IGERT: Training the Next Generation of Researchers in Cellular & Molecular Mechanics and BioNanotechnology, which contributed by providing travel support to work with the Screen Lab at Queen Mary University of London, UK, where a substantial amount of this work took place. L.C.M. also acknowledges support from the University of Illinois via the Support for Under-Represented Groups in Engineering (SURGE) Fellowship and the DuPont Science and Engineering Fellowship programs.
Publisher Copyright:
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2016/7/20
Y1 - 2016/7/20
N2 - 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. In osteotendinous scaffolds, 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, in layered scaffolds 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.
AB - 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. In osteotendinous scaffolds, 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, in layered scaffolds 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.
KW - cell alignment
KW - cell–matrix interactions
KW - collagen scaffolds
KW - mesenchymal stem cells
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U2 - 10.1002/adhm.201600181
DO - 10.1002/adhm.201600181
M3 - Article
C2 - 27245787
AN - SCOPUS:84978708808
SN - 2192-2640
VL - 5
SP - 1731
EP - 1739
JO - Advanced healthcare materials
JF - Advanced healthcare materials
IS - 14
ER -