Magnetic actuated materials modulate inflammatory cues underlying human tendinopathy

INTRODUCTION: Tendinopathies represent half of all musculoskeletal injuries worldwide. Inflammation contributes to both tendon healing and to tendinopathy but the mechanisms leading to pathology are unknown. In previous studies, we showed that pulsed electromagnetic field (PEMF) actuation modulates tendon cell behaviour in inflammatory environments, and that PEMF actuated membranes could influence inflammation responses in a rat ectopic model [1]. Herein, we propose to investigate the synergistic action of PEMF and magnetic responsive membranes in i) tendon cells treated with IL-1 to mimic a tendinopathy environment and ii) the phenotype of macrophages cultured on the membranes. METHODS: Human tendon cells (hTDCs) were seeded (5000 cells/cm2) on membranes of starch and polycaprolactone impregnated with iron oxide nanoparticles before treatment with IL-1. Afterwards, hTDCs were exposed for 1h to a 5Hz 4mT PEMF with a 50% duty cycle. The phenotype of human macrophages on PEMF actuated membranes was assessed to confirm their immunomodulatory potential. RESULTS & DISCUSSION: The expression of pro-inflammatory (TNF, IL-6, IL-8, COX-2) and ECM remodeling (MMP-1,-2,-3 and TIMP-1) genes tend to decrease in PEMF actuated membranes, while anti-inflammatory gene expression (IL-4, IL-10) increases. Also, CD16++ and CD206+ were only detected in macrophages cultured on PEMF actuated membranes. CONCLUSIONS: PEMF actuated membranes show a modulatory effect on the inflammatory profile of hTDCs. The expression of anti-inflammatory/repair markers in macrophages highlights the immune modulatory potential of PEMF actuated membranes envisioning tendon healing strategies. ACKNOWLEDGEMENTS: FCT (PD/BD/ 128089/2016), Doctoral Program TERM (PD/59/ 2013), NORTE-01-0145-FEDER-000021, H2020 under the TEAMING Grant agreement No. 739572- The Discoveries CTR. Thank to Hospital da Prelada (Porto, Portugal). REFERENCES [1] Santos LJ et al. Nanomedicine. 2016; 11(9): 1107-1122