Dosed Myofascial Release in Three-Dimensional Bioengineered Tendons: Effects on Human Fibroblast Hyperplasia, Hypertrophy, and Cytokine Secretion

Objective: The purpose of this study was to investigate potential differences of magnitudes and durations associated with dosed myofascial release (MFR) on human fibroblast proliferation, hypertrophy, and cytokine secretions.

Methods: Bioengineered tendons (BETs) attached to nylon mesh anchors were strained uniaxially using a vacuum pressure designed to model MFR varying in magnitudes (0%, 3%, 6%, 9%, and 12% elongation) and durations (0.5 and 1-5 minutes). Conditioned media were analyzed for cytokine secretion via protein microarray (n = 2). Bioengineered tendons were weighted and fibroblasts extracted from the BET were assessed for total cell protein and proliferation via double-stranded DNA quantification (n = 5). All data were compared by a 1-way analysis of variance with post hoc Dunnett test and Student t test.

Results: Changing MFR magnitude and duration did not have an effect on total fibroblast cellular protein or DNA accumulation. However, we observed a stepwise increase in BET weight with higher-magnitude MFR treatments. Longer durations of MFR resulted in progressive increase in the secretions of angiogenin, interleukin (IL)-3, IL-8, growth colony-stimulating factor, and thymus activation-regulated chemokine. Alternatively, increasing strain magnitude induced secretions of IL-1β, monocyte chemoattractant cytokine, and regulated and normal T cell expressed and secreted chemotactic cytokine.

Conclusion: Cellular proliferation and hypertrophy were not significantly changed by any treatment. However, the change in total BET dry weight suggests that production of extracellular matrix protein may be up-regulated. Different MFR parameters induce secretions of a unique subset of cytokines and growth factors that can be further enhanced by increasing the magnitude and duration of treatment. If clinically translatable, these results suggest that variations to manual therapy biomechanical parameters may differentially affect physiological responses in vivo.