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Design of a Novel 3D Printed Bioactive Nanocomposite Scaffold for Improved Osteochondral Regeneration

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Abstract

Chronic and acute osteochondral defects as a result of osteoarthritis and trauma present a common and serious clinical problem due to the tissue’s inherent complexity and poor regenerative capacity. In addition, cells within the osteochondral tissue are in intimate contact with a 3D nanostructured extracellular matrix composed of numerous bioactive organic and inorganic components. As an emerging manufacturing technique, 3D printing offers great precision and control over the microarchitecture, shape, and composition of tissue scaffolds. Therefore, the objective of this study is to develop a biomimetic 3D printed nanocomposite scaffold with integrated differentiation cues for improved osteochondral tissue regeneration. Through the combination of novel nano-inks composed of organic and inorganic bioactive factors and advanced 3D printing, we have successfully fabricated a series of novel constructs which closely mimic the native 3D extracellular environment with hierarchical nanoroughness, microstructure, and spatiotemporal bioactive cues. Our results illustrate several key characteristics of the 3D printed nanocomposite scaffold to include improved mechanical properties as well as excellent cytocompatibility for enhanced human bone marrow-derived mesenchymal stem cell adhesion, proliferation, and osteochondral differentiation in vitro. The present work further illustrates the effectiveness of the scaffolds developed here as a promising and highly tunable platform for osteochondral tissue regeneration.

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Acknowledgments

The authors would like to thank NIH Director’s New Innovator Award (DP2EB020549) and GW Institute for Biomedical Engineering for financial support.

Conflict of interest

Nathan J. Castro, Romil Patel and Lijie Grace Zhang declare that they have no conflicts of interest.

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No human or animal studies were carried out by the authors for this article.

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Correspondence to Lijie Grace Zhang.

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Associate Editor Christine Schmidt oversaw the review of this article.

This article is part of the 2015 Young Innovators Issue.

Lijie Grace Zhang is an assistant professor in the Department of Mechanical and Aerospace Engineering, Department of Biomedical Engineering and Department of Medicine at the George Washington University. She obtained her Ph.D. in Biomedical Engineering at Brown University in 2009. Dr. Zhang joined GW in 2010, after finishing her postdoctoral training at Rice University and Harvard Medical School. Currently she directs the Bioengineering Laboratory for Nanomedicine and Tissue Engineering at GW. She has received the NIH Director’s New Innovator Award, GW SEAS Outstanding Young Researcher Award, John Haddad Young Investigator Award by American Society for Bone and Mineral Research, the Early Career Award from the International Journal of Nanomedicine, Ralph E. Powe Junior Faculty Enhancement Award by the Oak Ridge Associated Universities Organization, Joukowsky Family Foundation Outstanding Dissertation Award at Brown and the Sigma Xi Award. Her research interests include nanomaterials, 3D bioprinting, complex tissue engineering, stem cell engineering, drug delivery and breast cancer bone metastasis. Dr. Zhang has authored 2 books, over 60 journal papers, book chapters and conference proceedings, 3 patents and has presented her work on over 150 conferences, university and institutes.

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Castro, N.J., Patel, R. & Zhang, L.G. Design of a Novel 3D Printed Bioactive Nanocomposite Scaffold for Improved Osteochondral Regeneration. Cel. Mol. Bioeng. 8, 416–432 (2015). https://doi.org/10.1007/s12195-015-0389-4

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