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3D-Printed Bioreactor Enhances Potential for Tendon Tissue Engineering

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Abstract

Bioreactors have immense value within tissue engineering by enabling important control over design inputs within a microenvironment; however, they are often complex and expensive. Herein, we demonstrate a strategy where a bioreactor was 3D-printed as a means to provide an accessible route to culture scaffolds under physiological inputs and to determine an ideal tendon scaffold structure based on remodeling and degradation events. Furthermore, real-time monitoring of tissue remodeling is introduced through the bioreactor design. Following in vitro uniaxial stretch conditioning, scaffolds were positively altered to reflect improved biomechanical function, enhanced extracellular matrix (ECM) content, and increased mechanical properties of elastic moduli. A bioreactor was constructed to meet the following criteria: real-time readout of resistance, ability to be easily cleaned and sterilized, control of strain, speed, and time parameters, and capability to withstand 3 weeks of continuous load with minimal maintenance. The scaffolds cultured in a dynamic setting showed improved mechanics and promising ECM and collagen content generated. Overall, the bioreactor was effective as a tool to provide mechanical culture conditions that promote the tendon cell niche. The bioreactor supports the scaffolds as a possible therapeutic venture in tendon tissue engineering. Additionally, the 3D-printed bioreactor is a significant contribution to the tissue engineering field by making dynamic culturing more accessible for researchers.

Lay Summary

Bioreactors present physiological and dynamic conditions for tissue testing and are crucial in tissue engineering for product development, standardization, quality control, and large-scale synthesis. The low-cost, 3D-printed, programmable bioreactor provides cyclic stretch to scaffolds with real-time resistance readout and demonstrates tissue changes over time. The bioreactor enhances scaffold biomechanics and biofunctionality towards natural tendon by promoting cell alignment through mechanical force. The design components are culture chamber for tendon constructs, motor control of uniaxial stretching, and a base for stabilization. The results from conditioning scaffolds in the bioreactor lend to a better understanding of how specific inputs affect tissue outcomes.

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Acknowledgments

Gene Gerber, Tony Banik, Andrew Higgins, Jordan Dover, Gary Meyers, Austin Greever, Greg Learn, Eric VanArsdale, Michele Herneisey, and Nimesh Lad are acknowledged for their input on the bioreactor design and iterations. John Cantolina is recognized for his help with histology.

Funding

This material was based upon work supported by R03 AR065192 and the National Science Foundation (NSF) under Grant No. DGE1255832. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the NSF.

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Authors and Affiliations

  1. Department of Biomedical Engineering, The Pennsylvania State University, 122 CBE Building, University Park, PA, 16802, USA

    Brittany L. Banik & Justin L. Brown

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  1. Brittany L. Banik
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  2. Justin L. Brown
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Correspondence to Justin L. Brown.

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Description of Future Works

Future works to expand this project include the following: integrating a Graphic User Interface (GUI) for the bioreactor to simplify programming, testing silk as a scaffold material, and consideration to overall scaffold design that would incorporate the enthesis.

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Banik, B.L., Brown, J.L. 3D-Printed Bioreactor Enhances Potential for Tendon Tissue Engineering. Regen. Eng. Transl. Med. 6, 419–428 (2020). https://doi.org/10.1007/s40883-019-00145-y

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  • DOI: https://doi.org/10.1007/s40883-019-00145-y

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