Using Functional Tissue Engineering and Bioreactors to Mechanically Stimulate Tissue-Engineered Constructs

TLDR

Bioreactors precondition tissue‑engineered constructs to enhance their integrity and repair potential. The study proposes criteria for preconditioning TECs and outlines future improvements to bioreactors for more functional tissue creation. The authors design bioreactors that control the mechanical environment, deliver precise displacements—including ADL‑like strain patterns—and allow individual force recording, applying these criteria to three bioreactors and an incubator integrated with electromagnetic stimulators. The system successfully stretched TECs, replicated in‑vivo patellar tendon strains, monitored cellular activity, improved TEC and PT repair stiffness with correlated increases, and maintained cell viability comparable to commercial incubators, though it cannot directly measure TEC forces.

Abstract

Bioreactors precondition tissue-engineered constructs (TECs) to improve integrity and hopefully repair. In this paper, we use functional tissue engineering to suggest criteria for preconditioning TECs. Bioreactors should (1) control environment during mechanical stimulation; (2) stimulate multiple constructs with identical or individual waveforms; (3) deliver precise displacements, including those that mimic in vivo activities of daily living (ADLs); and (4) adjust displacement patterns based on reaction loads and biological activity. We apply these criteria to three bioreactors. We have placed a pneumatic stimulator in a conventional incubator and stretched four constructs in each of five silicone dishes. We have also programmed displacement-limited stimuli that replicate frequencies and peak in vivo patellar tendon (PT) strains. Cellular activity can be monitored from spent media. However, our design prevents direct TEC force measurement. We have improved TEC stiffness as well as PT repair stiffness and shown correlations between the two. We have also designed an incubator to fit within each of two electromagnetic stimulators. Each incubator provides cell viability like a commercial incubator. Multiple constructs are stimulated with precise displacements that can mimic ADL strain patterns and record individual forces. Future bioreactors could be further improved by controlling and measuring TEC displacements and forces to create more functional tissues for surgeons and their patients.