Abstract
Successful engineering of load-bearing tissues requires recapitulation of their complex mechanical functions. Given the intimate relationship between function and form, biomimetic materials that replicate anatomic form are of great interest for tissue engineering applications. However, for complex tissues such as the annulus fibrosus, scaffolds have failed to capture their multi-scale structural hierarchy. Consequently, engineered tissues have yet to reach functional equivalence with their native counterparts. Here, we present a novel strategy for annulus fibrosus tissue engineering that replicates this hierarchy with anisotropic nanofibrous laminates seeded with mesenchymal stem cells. These scaffolds directed the deposition of an organized, collagen-rich extracellular matrix that mimicked the angle-ply, multi-lamellar architecture and achieved mechanical parity with native tissue after 10 weeks of in vitro culture. Furthermore, we identified a novel role for inter-lamellar shearing in reinforcing the tensile response of biologic laminates, a mechanism that has not previously been considered for these tissues.
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Acknowledgements
The authors would like to thank J. B. Stambough for assistance with data collection. This work was financially supported by the National Institutes of Health (EB02425), the Aircast Foundation and the Penn Center for Musculoskeletal Disorders (AR050950).
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Experiments were conceived by N.L.N, B.M.B., D.M.E. and R.L.M. Studies on the evolving properties of parallel and opposing bilayers were executed by N.L.N and S.S., with assistance from E.E.W. on histologic analyses. Acellular tensile studies and cell-seeded lap testing studies were carried out by N.L.N. and B.M.B., respectively. The manuscript was prepared by N.L.N., D.M.E. and R.L.M.
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Nerurkar, N., Baker, B., Sen, S. et al. Nanofibrous biologic laminates replicate the form and function of the annulus fibrosus. Nature Mater 8, 986–992 (2009). https://doi.org/10.1038/nmat2558
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DOI: https://doi.org/10.1038/nmat2558
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