3D-Printed Bioreactor Enhances Potential for Tendon Tissue Engineering

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. 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.