The Design and Development of a High-Throughput Magneto-Mechanostimulation Device for Cartilage Tissue Engineering

Abstract

To recapitulate the in vivo environment and create neo-organoids that replace lost or damaged tissue requires the engineering of devices, which provide appropriate biophysical cues. To date, bioreactors for cartilage tissue engineering have focused primarily on biomechanical stimulation. There is a significant need for improved devices for articular cartilage tissue engineering capable of simultaneously applying multiple biophysical (electrokinetic and mechanical) stimuli. We have developed a novel high-throughput magnetomechanostimulation bioreactor, capable of applying static and time-varying magnetic fields, as well as multiple and independently adjustable mechanical loading regimens. The device consists of an array of 18 individual stations, each of which uses contactless magnetic actuation and has an integrated Hall Effect sensing system, enabling the real-time measurements of applied field, force, and construct thickness, and hence, the indirect measurement of construct mechanical properties. Validation tests showed precise measurements of thickness, within 14 mm of gold standard calliper measurements; further, applied force was measured to be within 0.04 N of desired force over a half hour dynamic loading, which was repeatable over a 3-week test period. Finally, construct material properties measured using the bioreactor were not significantly different ( p = 0.97) from those measured using a standard materials testing machine. We present a new method for articular cartilage-specific bioreactor design, integrating combinatorial magnetomechanostimulation, which is very attractive from functional and cost viewpoints.

The Application of Bioreactors for Cartilage Tissue Engineering: Advances, Limitations, and Future Perspectives

“…Recent studies have found that magnetic fields affect cells, tissues, and entire organisms, including the formation of the extracellular matrix of hyaline cartilage, proliferation of bovine chondrocytes, and the synthesis of proteoglycan [ 29 , 30 ]. Magnetic field bioreactors are advantageous, because they can meet the requirement of sterile culture conditions by contactless culture [ 31 , 32 ]. Most of them consist of one or a group of permanent magnets that influence the behavior of cells through static or dynamic magnetic field strengths ( Figure 1(d) ).…”

“…For example, Brady et al constructed a novel high-throughput magnetomechanical stimulation bioreactor. Validation tests showed that the bioreactor provided a unique platform for researchers to study the combined effects of electrical phenomena and mechanical stimulation [ 32 ]. In another study, however, Dikina et al investigated a variable magnetic field bioreactor composed of permanent magnets that were used for the culture of scaffold-free, high-density hMSC sheets, and the results showed that the bioreactor did not enhance chondrogenesis in the cell-only sheets.…”

Review: bioreactor design towards generation of relevant engineered tissues: focus on clinical translation

“…Similarly, Brady et al . () designed and validated a high‐throughput bioreactor platform for the application of multiple magnetic fields and mechanical loading regimens simultaneously in multiple chambers with independent control for engineering functional cartilage tissues. In addition to enabling parametric optimization studies, the multi‐array configuration could also be potentially used for drug and toxicology studies with disease models (Domansky et al , ).…”

“…For instance, Pavesi et al (2014) developed a multichambered device with adaptable, independent culture chambers to test various electrical stimulation protocols simultaneously for stem cell differentiation towards myocardial phenotype. Similarly, Brady et al (2014) designed and validated a high-throughput bioreactor platform for the application of multiple magnetic fields and mechanical loading regimens simultaneously in multiple chambers with independent control for engineering functional cartilage tissues. In addition to enabling parametric optimization studies, the multi-array configuration could also be potentially used for drug and toxicology studies with disease models (Domansky et al, 2010).…”

A Perfusion Bioreactor System for Cell Seeding and Oxygen-Controlled Cultivation of Three-Dimensional Cell Cultures

“… 9 , 10 , 30–32 However, to display variations in an oxygen-controlled environment, bioreactors within a system have to be operating independently. Whereas the independent operation of parallel running bioreactors is described for mechanical stimuli, 33 no such design is available for oxygen-controlled 3D cell culture.…”