Casey Hofhenke

REPAREL TECHNOLOGY REVIEW Elemental Lessons from Copper We’ve all seen those late night informercials and ESPN commercials advertising Copper infused products. Copper is pseudoscience and has been disproven clinically in multiple situations, including a double-blind study on their use in bracelets.17 After the initial consumer craze others moved into the market infused compression garments with Copper. Most notably was Tommie Copper who made broad claims on the effectivity of their products for pain relief for not only general inflammation, but Fibromyalgia, Multiple Sclerosis, and Rheumatoid Arthritis. The FTC does not take such marketing claims lightly and filed a class action law suit for $1.25M in December of 2015 for the false or unsubstantiated claims that the copper in the apparel relieves pain, that wearing the garments provides relief from chronic or severe pain and from pain and inflammation caused by serious diseases, and that the garments provide pain relief comparable to – or even better than – drugs or surgery.3 Since then, other companies have come on the market with similar appeal but instead leaning on the market approved benefits of compression (increase circulation/oxygenation to reduce swelling and aid in recovery) and copper (anti-odor/anti-bacterial). The wide promotion of these products and their celebrity endorsement has sold millions of sleeves, but still perceived to pseudoscience and endorsed in the medical community as nothing more than placebo or proprioceptive. Some patients have experienced positive results. Due to the nature of copper as a conductor, possessing the ability to retain heat, perceived benefits are likely by maintaining warmth to a joint which in many cases is beneficial in application. Reparel Materials Since day one, Reparel has approached the market cautiously. After compiling our materials and testing through observation and anecdotal outcomes for both acute and degenerative inflammation, it was clear that Reparel was eliciting a physiological response in the body that was effective in reducing common musculoskeletal inflammation, both for post-operative use and conservative treatments. Reparel’s mission is to validate the use of Reparel in clinical settings and avoid the retail pitfalls of massmarket. Fundamentally, the material used in Reparel fabric is vastly different than anything else on the market. We have selected specific materials for the ability to reflect energy. We use a propriety blend of elemental semi-conductors which are ground to nanoparticles and embedded in the fibers of the product. The characteristics of semi-conductors are both thermo-conductive and have a high reflectivity. Meaning when thermal energy is absorbed it will reflect that energy non-thermally on a photonic wavelength. To prove the mechanism of action behind the Reparel material we measured the reflectance and wavelength on the electro-magnetic wave spectrum. Performed at the Colorado School of Minds using a Fourier Transform Infrared spectroscopy we were able to identify the output of Reparel fabric (two specific compositions) when warmed to 37˚C to match the normal radiation of the human body.14 In Figure 1 of the CSOM data we identified that Fabric 1 reflected energy significantly in the Near Infrared (NIR) range with rising reflectance around 680nm and peaks around 800nm. Fabric 2 did not reflect in the NIR range when heated to normal temperature but did peak in Mid Infrared range and beyond. Both materials appear to reflect in the MIR and likely the Far Infrared range. (Figure 1) Further exploration would include the measurement in the FIR as well as potential variance at high temperatures to mimic the body heat in situations of acute inflammation when heat is more present. Anecdotally we have observed that the greater reflectance (Fabric 1) is best suited for inflammatory conditions that do not have normal markers of acute inflammation (ie. heat), utilized for degenerative inflammation (ie. tendinopathy and osteoarthritis). We have positioned Fabric 2 with the lower reflectance for acute inflammation since heat is at a greater intensity the higher reflectance is not necessary. Infrared Energy and Photobiomodulation Infrared Radiation (IR) is electromagnetic radiation with wavelengths between 760nm and 100,000nm. Increasing evidence suggests that IR can carry out photostimulation or photobiomodulation effects particularly benefiting neural stimulation and wound healing.1 Original this was characterized as Low Level Laser Therapy or Cold Laser, but with increasing mechanisms and invention of devices that do not require a power source, Photobiomodulation (PBM) therapy emerged.2 The use of this term is key, as it distinguishes photobiomodulation therapy from the previous use of light-based devices for simple heating of tissues. A more comprehensive definition would be ‘a form of light therapy that utilizes non-ionizing forms of light sources on the infrared spectrum. It is a nonthermal process involving endogenous chromophores eliciting photophysical and photochemical events at various biologic scales. The process results in beneficial therapeutic outcomes including but not limited to the alleviation of pain or inflammation, immunomodulation, and promotion of wound healing and tissue regeneration,’9 (Figure 3) Photobiomodulation in Clinical Settings Soon after the discovery of lasers in the 1960s it was realized that laser therapy (now PBMT) had the potential to improve wound healing and reduce pain, inflammation and swelling. Although Low-Level Laser Therapy (LLLT) has numerous studies and is used to treat a wide variety of ailment, it remains controversial due to the lack of understanding on its exact biochemical mechanisms and a large variance of parameters such as wavelength, fluence, power, and timing of application.6 With over 4000 studies on pub.med.gov, there is now more hard evidence on the basic mechanisms, pre-clinical applications, and clinical benefits of LLLT / PBMT. Several reviews referenced in this study as well numerous in vitro cellular studies, animal studies, and human trials.12 Sometimes inconsistent, yet all are promising and point to several modalities and applications that could greatly impact the medical community and soon become a new standard of care. With the advantage of being non-invasive, the applications of PBM are broad, going from pain relief to promoting the recovery of tendinopathies, nerve injuries, osteoarthritis, and wound healing. Parameters and Mechanisms of Action of PBM Low-level light therapy has always utilized wavelengths in the Near Infrared Range as an optical window has been identified between -nm). Effective tissue penetration is maximized in this range, specifically wavelengths in the range of 780-950nm that are used to treat deep tissues.6 Wavelengths at 760-820nm have been identified to be the most efficient modulators of mitochondrial function, stimulating cellular energy metabolism and energy production through photoacceptor molecule (chromophore) cytochrome c oxidase in the electron chain transport.11 (Figure 4) Mitochrondia is the powerhouse of the cell as they convert food molecules and oxygen intro energy (ATP) by oxidative phosphorylation. PBM increases the availability of electrons for the reduction of molecular oxygen in the center of cytochrome c oxidase, increasing the mitochondrial membrane potential and the levels of ATP, cAMP, ROS, and Nitric Oxide (NO).10 (Figure 2.) NO is a well-known potent vasodilator facilitating the relaxation of smooth muscles cells in the lining of blood vessels and lymphatic vessels.13 Far infrared (FIR) is also absorbed by the human body but likely not through the same mechanisms as NIR. The principle chromophore at FIR wavelengths is water which could alter several signaling pathways that could have positive therapeutic effects. The body experiences its energy as a gentle radiant heat which penetrate up 4 cm beneath this skin without producing detectable skin heating.4 Water light interactions in the oxygen-independent pathway, lead to photoinduced non-linear oscillations in water that could provide energy for cellular reactions, including metabolism and signaling. Although much of the theorized applications and mechanisms appear to be similar to PBMT, there is still much more data required for scientific certainty.4 Application There are four clinical targets for PBMT: 1. 2. 3. 4. The site of injury to promote healing, remodeling and reduce inflammation. Lymph nodes to reduce edema and inflammation Nerves to induce analgesia Trigger points to reduce tenderness and relax contracted muscle fibers. The overall positive, short term clinical studies in addition to strong laboratory studies should give the clinical confidence that LLLT may be beneficial for many individuals suffering from musculoskeletal pain, regardless of the cause.7 Inflammation Protocols The general practice has been to reduce inflammation but the problem with this approach is that preventing inflammation may hinder recovery. The focus should be to allow inflammatory processes to progress naturally rather than inhibit. Therapy should not be to obliterate the inflammatory response, but instead restore the normal regulation of inflammatory responses. The use of existing therapies, particularly NSAIDS, to block inflammation appears to have negative effects on regenerative processes.18 Incorrectly regulated, persistent inflammation is a major contributor to the pathogenesis of many musculoskeletal disease including age-related pathologies such as osteoporosis and osteoarthritis. The mechanisms are complex but closely associated with mitochondrial dysfunction.8 It is important to recognize that inflammation is the first stage in the healing process and regulation of this process would include successful progression to the latter phases, repair/proliferation and remodeling. With potential adverse effects of various therapies, PBM has well established studies demonstrating the reduction of edema, and reductions in markers of oxidative stress and pro-inflammatory cytokines with an almost complete lack of reported adverse effects.5 This especially deserves consideration for not only joint inflammation, but acute inflammatory symptoms post-operatively. Current protocols of pain relief like ice and cold therapy could retard proliferation at the early stages of regeneration.16 Whether in combination or independent of, PBM therapies can ensure proper regulation of the inflammatory pathways to promote the natural healing process. Photobiomodulation in Apparel In recent years nanotechnology development has provided new methods of providing light therapy in a comfortable and easy form. In general, the mechanism of action of IR radiating materials is to transform heat energy from the body (convection and conduction) into radiation within the IR wavelength to induce homeostasis and photobiomodulation. The use of such materials is possibly helpful to enhance blood circulation and the metabolism of the human body.1 This mode of application could be more flexible method of portable, lifestyle-enhancing applications for treating a variety of medical applications independent of a power source. Potentially reducing the reliance of compression garments which appear to function more by preventing distention of veins, rather than acute swelling. It has even been determined that regardless of pressure applied, the most important factor in selecting a garment for such purpose is patient compliance.15 Conclusion The potential applications of technologies such as Reparel in tandem of the emergence of Photobiomodulation and its acceptance by the medical community create vast opportunities for various conditions, as well as the disruption of outdated protocols and treatment methods. Furthermore, the Reparel technology is only in its infancy. New materials can be sourced and include with increased wearable technologies and the identification of other wearable therapeutics. Iterations of compositions, materials, and even geometrical shape allow for differentiation of wavelengths and intensities for specification to various conditions or desired outcomes. References 1. B., J. P. (2018, May 01). Biological Effect and Medical Applications of Infrared Radiation. Author Manuscript. PubMed Central. 2. Biophotonics, J. (2016). Photobiomodulation or Low-Level Laser Therapy. Author Manuscript,-. Cooper, L. (2015, Decemeber 18). Exercise & Fitness. Retrieved from Consumer Reports: https://www.consumerreports.org/exercise-fitness/copper-compression-sleeves-and-painrelief/ 4. Fatma Vatansever, M. R. (November 1 2012). Far infrared radiation (FIR): its biological effects and medical applications. Photonics Lasers Med,-. Hamblin, M. R. (2017). Mechanisms and applications of the anti-inflammatory effects of photobiomodulation. AIMS Biophys, 4(3):-. Hoon Chung, T. D.-Y. (2012). The Nuts and Bolts Of Low-Level Laser (light) Therapy. Annals of Biomedical Engineering,-. Howard B Cotler, R. T. (2015). The Use of Low Laser Therapy (LLLT) For Musculoskeletal Pain. MOJ Orthop Rheumatol, 2(5). 8. Jiri Gallo, M. R. (2017). Inflammation and its resolution and the musculoskeletal system. Journal of Orthopaedic Translation , 10, 52-67. 9. Juanita J. Anders, P. R. (2015). Low-Level Light/Laser Therapy Versus Photobiomodulation Therapy. Photomedicine and Laser Surgery, Volume 33, Number 4, 183-184. 10. Lucas Freitas De Freitas, M. R. (2016). Proposed Mechanisms of Photobiomodulation or LowLevel Light Therapy. IEEE J Sel Top Quantum Electron, 22(3). 11. Margaret T.T. Wong-Riles, H. L. (February 11 2006). Photobiomodulation Directly Benefits Primary Neurons Functionally Inactivated by Toxins. The Journal Of Biological Chemistry, Vol. 280 pp-. Michael R. Hamblin, P. (August 2010). Introduction to Experimental and Clinical Studies Using Low-Level Laser (Light) Therapy (LLLT). Lasers Surg Med, 42(6):-. Murad, F. (2011). Discovery of nitric oxide and cyclic GMP in cell signaling and their role in drug development. International Conference on Molecular Neurodegeneration (pp. 22-24). Shanghai, China: BioMed Central. 14. PHD, G. L. (2016). Optical Response of Reparel Fabrics, 0.3-2.5um. Golden, Colorado: Colorado School of Mines. 15. Rhys J. Morris, P. J. (2004). Evidence-Based Compression. Annals of Surgery, Volume 239 (2). 16. Ryo Takagi, N. F. (2011). Influence of icing on muscle regeneration after crush injury to skeletal muscles in rats. J Appl Physiol, 110:-. Stewart J. Richmond, S. G. (2013). Copper Bracelets and Magnetic Wrist Straps for Rheumatoid Arthritis - Analgesic and Ainti-Inflammatory Effects: A Randomised Double-Blind Placebo Controlled Crossover Trial. PLOS ONE, Volume 8 Issue 9. 18. Urso, M. L. (2013). Anti-inflammatory interventions and skeletal muscle injury: benefit or detriment? J Appl Physiol, 115: 920-928. FIGURE 3. The spectrum of electromagnetic radiation and some biological changes it may induce. Figure 4. Tissue optical window.