Bio-Oxidative solutions Inc.

Medical Properties for wound healing of "Electronically Modified Oxygen Derivatives" (EMOD's) :

1) Chemotaxis

Chemotaxis is movement of an organism in response to a chemical stimulus. In our case, we would like to induce Mesenchymal Stem Cells (MSC) to the wound bed for a regeneraton effect.  There is no other Growth Factor known to do this better then PDGF, as shown in the graph below. 

It has been shown time and time again the EMOD groups revealed increased expressions of PDGF, TGF-β, and VEGF when adminstered.  This according to the work of Hee Su Kim, Sun Up Noh, Ye Won Han, Kyoung Moon Kim, Hoon Kang, Hyung Ok Kim, and Young Min Park " Therapeutic Effects of Topical Application of Ozone on Acute Cutaneous Wound Healing"

"Fibroblasts have been known to play important roles in reepithelization, collagen fiber synthesis, extracellular matrix regeneration, remodeling of wounds, and for the release of such endogenous growth factors as FGF, PDGF, TGF-β, and VEGF (1, 25). In this study, increased expressions of PDGF and TGF-β were seen in the ozone group on day 7, which is correlated with increased staining intensity of collagen fibers and fibroblast proliferation on the same day. There were also increased expressions of PDGF and TGF-β in the epidermal keratinocytes and the hair follicular cells adjacent to the injury. These findings suggest that O₃ might induce expressions of PDGF and TGF-β from epidermal keratinocyte as well as from the dermal fibroblast at the injury site. In the present study, there was a relatively increased expression of VEGF in the epidermal keratinocytes of the ozone group on day 7"

The Graph is borrowed from Bio Mimetic website that shows adult stem cell migration in the precence of PDGF.

"PDGF is a potent mitogen of cells of mesenchymal (musculoskeletal) origin. In this study from Ozaki (2007) mesenchymal stem cells were separately exposed to multiple growth factors in a study used to acess cell proliferation."



Angiogenesis 

Tissue regeneration is dependent on the blood supply; this is why, in areas of no vascularization like the Knee, it is dificult to get a natural healing response, especially in older patients. VEGF is a molecule, which stimulates new blood vessels. When EMOD's are introduced in these hard to heal places, we do see a wound healing response due to the recruitment of Adult Stem cells to the wound site, based on the release of these type of growth factors. 

Bouletreau (2002), showed VEGF, production, is depended on PDGF.  This protein is necessary for the new formation of blood vessels. 

 In essence, the closure of cutaneous wounds involves complex tissue movements such as hemorrhage, inflammation, re-epithelization, granulation tissue formation, and the late remodeling phase of repair . These events involve coordination of dozens of types of cells and matrix proteins, which are all important to control stages of the repair process. Previous studies have demonstrated that endogenous growth factors, such as fibroblast growth factors (FGF) , platelet derived growth factors (PDGF) , transforming growth factor-β (TGF-β)  and vascular endothelial growth factors (VEGF)  are the important regulatory polypeptides for coordinating the healing process. They are released from macrophages, fibroblasts, and keratinocytes at the site of injury and they participate in the regulation of re-epithelization, granulation tissue formation, collagen synthesis and neovascularization.(1) However, we can aftically induce these esscianly growth factors for wound healing, by the indrotduction, of EMOD's.  This give us, the ability to start the wound healing process in areas, like the knee, or in the spine, where blood flow is limited.

It is also shown that exposure to oxygen free radicals is associated with activation of transcription factor NF-κB; this is important to regulate inflammatory responses and eventually the entire process of wound healing . It is shown that huge amounts of PDGF and TGF-β1 are released from platelets in the heparinized plasma of a limb ischemia patient after being exposed to oxygen free radicals. PDGF is the strongest chemo taxis agent that stimulate adult stem cell migration to the wound bed, It has been revealed that there were substantial increases of steady-state mRNA levels of TGF-β1 in the fibroblasts that were co-cultured with bronchoepithelial cells after O^-1  exposure . (1)

Free radical therapy facilitates acute cutaneous wound healing, and this is associated with growth factors such as FGF, PDGF, TGF-β and VEGF. The unique ability of oxygen free radicals also induce immune related messenger molecules called cytokines which comes from its action on the membranes of white cells . Examples of cytokines are gamma interferon, interleukin-2, colony stimulating factor, and TNF-alpha just to name a few.

These cytokines stimulate a powerful innate immune response that recruit white cells and neutriphills to the area and encourage phagocytosis.  White cells roll in a process called extravasation, where they are attracted to the gradient of Cytokines. PDGF and the other Growth factors that are released during this process are a strong chemo attractant for adult stem cells as shown by the graph above. This encourages differentiation and proliferation of the stem cell migration.

Radical stabilization technology now can harness your body's ability to stimulate a full regeneration effect of many of its tissues, including the hard tissues, like in the knee cartilage, or like in herniated disc area.

These type of treatments are gaining ground in the medical community, and has been shown for at for herniated disc repair, EMOD therapy has been, just effective as back surgery. 

For instance;  “At the 2009 scientific meeting of the Society of Interventional Radiology, Dr. Murphy presented findings after combining the results of several studies on oxygen-ozone treatment. His research team found that patients receiving oxygen-ozone treatments experienced similar outcomes, as far as pain and function, as patients who had a discectomy¹.” 

Our company is primed to profit from all these new findings. We have solved the stability and dosing problem that plauged these therpies from their inception. You cannot patent Free radicals, but you can patent, the stabilization of such and that’s what we did.  

So we are in a unique position in a multibillion dollar market place.

 1. “Therapeutic Effects of Topical Application of Ozone on Acute Cutaneous Wound Healing”
Hee Su Kim, Sun Up Noh, Ye Won Han, Kyoung Moon Kim, Hoon Kang, Hyung Ok Kim, and Young Min Park ,Korean Med Sci. 2009 June; 24(3): 368–374.  Published online 2009 June 12. doi:  10.3346/jkms.2009.24.3.368