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Biomimetic 3D-printed scaffolds for spinal cord injury repair

Nature Medicine volume 25, pages 263–269 (2019)Cite this article

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Abstract

Current methods for bioprinting functional tissue lack appropriate biofabrication techniques to build complex 3D microarchitectures essential for guiding cell growth and promoting tissue maturation1. 3D printing of central nervous system (CNS) structures has not been accomplished, possibly owing to the complexity of CNS architecture. Here, we report the use of a microscale continuous projection printing method (μCPP) to create a complex CNS structure for regenerative medicine applications in the spinal cord. μCPP can print 3D biomimetic hydrogel scaffolds tailored to the dimensions of the rodent spinal cord in 1.6 s and is scalable to human spinal cord sizes and lesion geometries. We tested the ability of µCPP 3D-printed scaffolds loaded with neural progenitor cells (NPCs) to support axon regeneration and form new ‘neural relays’ across sites of complete spinal cord injury in vivo in rodents1,2. We find that injured host axons regenerate into 3D biomimetic scaffolds and synapse onto NPCs implanted into the device and that implanted NPCs in turn extend axons out of the scaffold and into the host spinal cord below the injury to restore synaptic transmission and significantly improve functional outcomes. Thus, 3D biomimetic scaffolds offer a means of enhancing CNS regeneration through precision medicine.

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Fig. 1: The 3D-printed scaffold mimics the spinal cord architecture.
Fig. 2: Four weeks in vivo performance of empty 3D-printed scaffold implants.
Fig. 3: Four weeks in vivo performance of NPC-loaded 3D-printed scaffold implants.
Fig. 4: Long-term in vivo studies of 3D-printed scaffolds loaded with NPCs.

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Data availability

Data supporting the findings of this study are available from ykoffler@ucsd.edu on reasonable request. All requests for materials and data are promptly reviewed by the Office of Innovation and Commercialization—University of California San Diego to verify whether the request is subject to any intellectual property or confidentiality obligations. Any materials and data that can be shared will be released via a Material Transfer Agreement.

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Acknowledgements

We thank J. Liu for materials synthesis, J. Li, D. Xue and S. You for helpful discussion and CAD design, and R. Anderson for assistance in scanning electron microscopy. This work was supported in part by the NIH (R01EB021857, R21HD090662), the NSF (1547005, 1644967), the California Institute for Regenerative Medicine (RT3–07899) and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation. The electron micrographs were taken in the Cellular and Molecular Medicine Electron microscopy core facility, which is supported in part by National Institutes of Health Award number S10OD023527.

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Author notes

  1. These authors contributed equally: Jacob Koffler and Wei Zhu.

Authors and Affiliations

  1. Department of Neuroscience, University of California San Diego, La Jolla, CA, USA

    Jacob Koffler, Jennifer N. Dulin, John Brock, Lori Graham, Paul Lu & Mark H. Tuszynski

  2. Department of NanoEngineering, University of California San Diego, La Jolla, CA, USA

    Wei Zhu, Xin Qu & Shaochen Chen

  3. Department of Anesthesiology, University of California San Diego, La Jolla, CA, USA

    Oleksandr Platoshyn & Martin Marsala

  4. Mechanical Engineering Department, University of Michigan, Ann Arbor, MI, USA

    Jeff Sakamoto

  5. Veterans Affairs Medical Center, San Diego, CA, USA

    Mark H. Tuszynski

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Contributions

J.K. and W.Z. contributed equally to this work. J.K. managed the project, designed the study and scaffold, performed in vivo surgery, anatomical analyses and functional testing, and prepared the manuscript. W.Z. desgined and printed scaffolds and prepared the manuscript. X.Q. supported scaffold design and printing and reviewed the manuscript. O.P. and M.M. performed electrophysiology J.D. and J.B. traced the corticospinal system. L.G. and P.L. performed surgeries. J.S. prepared agarose scaffolds. S.C. supervised scaffold development and prepared the manuscript. M.H.T. managed the project, reviewed data and prepared the manuscript.

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Correspondence to Jacob Koffler, Shaochen Chen or Mark H. Tuszynski.

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3D printing of biomimetic spinal cord scaffold

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Koffler, J., Zhu, W., Qu, X. et al. Biomimetic 3D-printed scaffolds for spinal cord injury repair. Nat Med 25, 263–269 (2019). https://doi.org/10.1038/s41591-018-0296-z

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