Researchers from the 3B’s Research Group at the University of Minho, Portugal have created tissue-like sheets of human tendon cells and magnetic nanoparticles to study the effects of inflammation in tendon disorders [Vinhas et al., Acta Biomaterialia 131 (2021) 236-247, https://doi.org/10.1016/j.actbio.2021.06.036 ]. Inflammation is a central part of both healing and disease processes, so developing new models to understand its basis and the ability to control it is key to treatment.
“We used magnetically assisted cell sheets (magCSs) constructed from human tendon-derived cells (hTDCs) and magnetic nanoparticles (MNPs) to study inflammation activity [and] tendon cell responses in inflammatory environments, which have been associated to tendinopathic conditions,” says Ana I. Gonçalves.
The sheets are created by culturing tendon cells from human tissue samples and adding MNPs. The cell sheets are exposed to IL-1β, a well-known pro-inflammatory cytokine, to induce an inflammatory response and a pulsed electromagnetic field (PEMF), which is used for clinical treatments, stimulates the magnetic nanoparticles.
“We hypothesized that magCSs could be approached as a pathophysiological model of inflammation to study the onset of tendon lesions and the inflammatory molecules affecting injured tendons,” explains first author of the study, Adriana Vinhas.
The researchers found that the IL-1β-induced inflammatory response in tendon cells can be modulated by an applied PEMF in the physiological range generated by a commercial magnetic therapy device. The approach enables contactless stimulation of tendon cells in a tissue-like environment and direct actuation of cells involved in tissue formation and regeneration. Magnetic modulation of the cell sheets improves cellular organization, which is a sign of healthy tissue.
“The remote control of magCS [response] strengthens the role of PEMF in tendon therapies and highlights the promise of magCSs as a living patch to overcome sustained inflammatory events in affected tendons and to promote tendon repair and regeneration,” says co-author Márcia T. Rodrigues.
As well as serving as an in vitro model of inflammation for tendon tissues, magCSs could also form the basis of scaffold-free patches for tendon repair. The application of a controlled, external magnetic field on a magnetically enabled graft could mediate the inflammatory environment and, consequently, the healing response in a completely non-invasive and painless procedure.
“[This] technology has promise as a bio-instructive tool for both tendon disease modeling and the development of magnetically responsive living tendon substitutes with immunomodulatory action,” points out Manuela E. Gomes.
The magCSs simple, low-cost assembly process could be performed at any hospital with cell culture facilities, for implantation into patients, she adds. It offers a scaffold-free approach to tendon healing and repair after injury.
“We will explore the magCSs in tendon injury and their impact in ameliorating the healing process after injury,” she says.
The combination of cell sheets and magnetic-based technologies holds promise for instrumental bio-instructive tools for the development of magnetically responsive living tendon analogs.