Intermittent actuation attenuates fibrotic behaviour of myofibroblasts
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Author(s)
Ward, Niamh A.
Hanley, Shirley
Tarpey, Ruth
Schreiber, Lucien H.J.
O'Dwyer, Joanne
Roche, Ellen T.
Duffy, Garry P.
Dolan, Eimear B.
Date Issued
January 2024
Journal
Acta Biomaterialia
Publisher
Elsevier BV
Citation
Ward, Niamh A., Hanley, Shirley, Tarpey, Ruth, Schreiber, Lucien H.J., O'Dwyer, Joanne et al. 2024. "Intermittent actuation attenuates fibrotic behaviour of myofibroblasts." Acta Biomaterialia, 173.
Version
Final published version
Abstract
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. STATEMENT OF SIGNIFICANCE: A major barrier to the successful clinical translation of many implantable medical devices is the foreign body response (FBR) and resultant deposition of a hypo-permeable fibrotic capsule (FC) around the implant. Perturbation of the implant site using intermittent actuation (IA) of soft-robotic implants has previously been shown to modulate the FBR and reduce FC thickness. However, the mechanisms of action underlying this response were largely unknown. Here, we investigate how IA can alter the activity of myofibroblast cells, and ultimately suggest that there is a mechanical loading threshold within which their fibrotic behaviour can be modulated. These findings can be harnessed to improve functional outcomes for a wide range of medical implants, particularly drug delivery and cell encapsulation devices.
Subjects
Molecular Biology
Biomedical Engineering
Biochemistry
Biomaterials
General Medicine
Biotechnology
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Massachusetts Institute of Technology. Department of Mechanical Engineering
Harvard University--MIT Division of Health Sciences and Technology
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.actbio.2023.11.017
