Effect of pulsed electromagnetic field treatment on programmed resolution of inflammation pathway markers in human cells in culture

Nicole J Kubat,1 John Moffett,2 Linley M Fray2 1Nicole Kubat Consulting, Pasadena, CA, USA; 2Life Science Department, Regenesis Biomedical, Inc., Scottsdale, AZ, USA Abstract: Inflammation is a complex process involving distinct but overlapping biochemical and molecular events that are highly regulated. Pulsed electromagnetic field (PEMF) therapy is increasingly used to treat pain and edema associated with inflammation following surgery involving soft tissue. However, the molecular and cellular effects of PEMF therapy on pathways involved in the resolution of inflammation are poorly understood. Using cell culture lines relevant to trauma-induced inflammation of the skin (human dermal fibroblasts, human epidermal keratinocytes, and human mononuclear cells), we investigated the effect of PEMF on gene expression involved in the acute and resolution phases of inflammation. We found that PEMF treatment was followed by changes in the relative amount of messenger (m)RNAs encoding enzymes involved in heme catabolism and removal of reactive oxygen species, including an increase in heme oxygenase 1 and superoxide dismutase 3 mRNAs, in all cell types examined 2 hours after PEMF treatment. A relative increase in mRNAs encoding enzymes involved in lipid mediator biosynthesis was also observed, including an increase in arachidonate 12- and 15-lipoxygenase mRNAs in dermal fibroblasts and epidermal keratinocytes, respectively. The relative amount of both of these lipoxygenase mRNAs was elevated in mononuclear cells following PEMF treatment relative to nontreated cells. PEMF treatment was also followed by changes in the mRNA levels of several cytokines. A decrease in the relative amount of interleukin 1 beta mRNA was observed in mononuclear cells, similar to that previously reported for epidermal keratinocytes and dermal fibroblasts. Based on our results, we propose a model in which PEMF therapy may promote chronic inflammation resolution by mediating gene expression changes important for inhibiting and resolving inflammation. Keywords: acute inflammation, resolution phase, heme oxygenase, reactive oxygen species, eicosanoids, resolvins, cytokines, lipid mediator

An open-label pilot study of pulsed electromagnetic field therapy in the treatment of failed back surgery syndrome pain

Wayne L Harper,1 William K Schmidt,2 Nicole J Kubat,3 Richard A Isenberg41Tarheel Clinical Research, LLC, Raleigh, NC, USA; 2NorthStar Consulting, LLC, Davis, CA, USA; 3Nicole Kubat Consulting, Pasadena, CA, USA; 4Regenesis Biomedical, Inc., Scottsdale, AZ, USAAbstract: Persistent pain following back surgery remains a major treatment challenge. The primary objective of this open-label exploratory study was to investigate the analgesic effectiveness of pulsed electromagnetic field therapy administered twice daily over a 45-day period in 34 subjects (68% female) with persistent or recurrent pain following back surgery. A secondary goal was to guide the design of future randomized controlled trials that could target responsive subpopulations. All predefined primary and secondary outcomes, including change in pain intensity (PI), physical function (Oswestry Disability Index), analgesic consumption, and overall well-being (Patient Global Impression of Change), are reported. A responder analysis (≥30% reduction in PI versus baseline) was added as a post hoc evaluation. Safety outcomes, as well as results of a cost-avoidance survey, are also summarized. Of the 30 per-protocol subjects who completed the study, 33% reported a clinically meaningful (≥30%) reduction in PI. A higher response rate (60%) was reported for subjects who had undergone discectomy prior to the trial compared to subjects who had undergone other types of surgical interventions (decompression or fusion) without discectomy. Improvements in PI were paralleled by improvements in secondary outcomes. Relative to baseline, responders reported an average 44% and 55% reduction in back PI and leg PI (respectively), and an average 13% improvement in Oswestry Disability Index scores. In the per-protocol population, 50% of responders and 12% of nonresponders reported less analgesia consumption at the end of treatment versus baseline. Sixty-seven percent of per-protocol responders and 0% of nonresponders reported clinically meaningful improvement in overall well-being on the Patient Global Impression of Change scale.Keywords: failed back surgery syndrome, pain management, pulsed electromagnetic field therapy, PEM

In vitro and in vivo assessment of magnetically actuated biomaterials and prospects in tendon healing

Aim: To expand our understanding on the effect of magnetically actuated biomaterials in stem cells, inflammation and fibrous tissue growth. Materials & methods: Magnetic biomaterials were obtained by doping iron oxide particles into starch poly-ϵ-caprolactone (SPCL) to create two formulations, magSPCL-1.8 and 3.6. Stem cell behavior was assessed in vitro and the inflammatory response, subcutaneously in Wistar rats. Results: Metabolic activity and proliferation increased significantly overtime in SPCL and magSPCL-1.8. Electromagnetic fields attenuated the presence of mast cells and macrophages in tissues surrounding SPCL and magSPCL-1.8, between weeks 1 and 9. Macrophage reduction was more pronounced for magSPCL-1.8, which could explain why this material prevented growth of fibrous tissue overtime. Conclusion: Magnetically actuated biomaterials have potential to modulate inflammation and the growth of fibrous tissue.This work was supported by POLARIS funded under FP7-REPGOT and Incentivo/SAU/LA0026/2014 from the Foundation for Science and Technology. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.info:eu-repo/semantics/publishedVersio