Intermittent actuation attenuates fibrotic behaviour of myofibroblasts

• DOI: 10.1016/j.actbio.2023.11.017
• Publication Date: 2023-11-14T19:43:26Z
• Authors: Niamh A. Ward; Shirley Hanley; Ruth Tarpey; Lucien H.J. Schre...; Joanne O'Dwyer; Ellen T. Roche; Garry P. Duffy; Eimear B. Dolan
• Keywords: Myofibroblast; Biomedical Engineering; 610; General Medicine; Biochemistry; Fibrosis; Mechanical loading; 3. Good health; Biomaterials; 616; Foreign body response; Collagen; Molecular Biology; Biotechnology

The foreign body response (FBR) to implanted materials culminates in the deposition of a hypo-permeable, collagen rich fibrotic capsule by myofibroblast cells at the implant site. The fibrotic capsule can be deleterious to the function of some medical implants as it can isolate the implant from the host environment. Modulation of fibrotic capsule formation has been achieved using intermittent actuation of drug delivery implants, however the mechanisms underlying this response are not well understood. Here, we use analytical, computational, and in vitro models to understand the response of human myofibroblasts (WPMY-1 stromal cell line) to intermittent actuation using soft robotics and investigate how actuation can alter the secretion of collagen and pro/anti-inflammatory cytokines by these cells. Our findings suggest that there is a mechanical loading threshold that can modulate the fibrotic behaviour of myofibroblasts, by reducing the secretion of soluble collagen, transforming growth factor beta-1 and interleukin 1-beta, and upregulating the anti-inflammatory interleukin-10. By improving our understanding of how cells involved in the FBR respond to mechanical actuation, we can harness this technology to improve functional outcomes for a wide range of implanted medical device applications including drug delivery and cell encapsulation platforms.