ARP History - Scientific Basis

The cellular processes of tissue and bone healing are complex and multifactorial. The scientific basis for ARP treatment is the positive cellular effects of direct current electrical fields on these processes. Direct current has been shown to affect cellular migration and orientation, endothelialization, protein synthesis, and calcium regulation, as well as stimulation of new bone formation and fracture healing.(4,6,7,10,18,19,21,22,24,25)

The initial response after injury is coagulation modulated by plasma platelet cells that form fibrin clots to stop bleeding. The clots attract polymorphonuclear neutrophils (PMNs) and fibroblasts that, in turn, adhere to the clots forming a fibrin gel. The PMNs consume bacteria and wound debris by secreting proteases.

Platelets also release growth factors that attract monocytes to the site of injury. Monocytes mature into macrophages that become the controlling cells in tissue healing. Macrophages continue the process of bacteria phagocytosis and cleaning of wound debris and also secrete growth factors that attract and activate fibroblasts.

Fibroblasts proliferate and migrate, and produce a collagen matrix. Concomitantly, endothelial cells migrate to the collagen matrix to produce new blood vessels in this matrix. Granulation tissue is formed composed of fibroblasts, endothelial cells, PMNs, and a collagen matrix.

Direct current electrical fields can modulate a number of factors involved in the healing response. A major process that is affected by direct current is cellular migration and orientation. Cooper and Keller, working with amphibian neural crest cells exposed to a direct current field, demonstrated a migration of cells towards the cathode with a resultant perpendicular cellular orientation.(7) In further studies, Cooper and Schliwa concluded that cell locomotion could be controlled with manipulation of the direct current field.(8) This process, called galvanotaxis, has been demonstrated also in neutrophils, macrophages, and fibroblasts.(10,18,21,22,23)

Direct current can also produce changes in endothelialization. Nannmark et al reported an increased permeability to macromolecules, and changes in capillary permeability to white blood cells with exposure to low levels of direct current.(19) Direct current can affect the migration of endothelial cells in vitro.(24)

Intracellular processes are also affected by exposure to direct current. Cheng et al established that relatively low levels of direct current can raise the adenosine triphosphate (ATP) level almost 500 % and increase protein synthesis and membrane transport.(6) Bourguignon et al demonstrated an uncapping of insulin receptors on the cell membrane and enhancement of protein and DNA synthesis within the first minute after direct current stimulation.(4)

New bone formation and fracture healing are positively affected by the application of a direct current electrical field.(11,12,14,17) The net effect of direct current on bone is an increase in osteoblastic activity and new bone formation around the cathode. These effects are optimally demonstrated with a current level of 5 to 20 micro amps. Studies have shown increased spinal fusion rates, and increased healing of fracture nonunions.(5,9,13)

The scientific basis for the use of direct current stimulation in tissue healing has long been established. The clinical problem has been in the application of the direct current without severe discomfort and skin damage. With precise application of an ingenious, patented background waveform, ARP technology allows clinically appropriate levels of direct current to be delivered to tissues safely.

References
ARP is the culmination of an immense body of research comprising the science behind the technology:

1. Bassett CAL, Hermann I. The effect of electrostatic fields on macromolecular synthesis by fibroblasts in vitro. J Cell Biol, 329: 9, 1968.

2. Borgens RB, Vanable JW, Jaffe LF. Bioelectricity and regeneration. Large currents leave the stumps of regenerating newt limbs. Proc Natl Acad Sci USA, 74: 4528-4532, 1977.

3. Borgens RB, Chapter 5: Integumentary potentials and Wound Healing in Electric Fields in Vertebrate Repair: Natural and Applied Voltages in Vertebrate Regeneration and Healing. Borgens RB, Robinson KR, Vanable JW, McGinis ME, McCaig CD (eds). New York, NY, Alan R. Liss, pp 171-224, 1989.

4. Bourguignon GJ, Wenche JY, and Bourguignon L. Electrical stimulation of human fibroblasts cause an increase in calcium influx and the exposure of additional insulin receptors. J Cellular Physiology, 140: 379-385,1989.

5. Brighton CT. Current concepts review: The treatment of nonunions with electricity. J Bone Joint Surg, 62A: 847-851, 1981.

6. Cheng N, et al. The effect of electrocurrents on ATP generation protein synthesis, and membrane transport in rat skin. Clinical Orthopedics, 171: 264-272, 1982.

7. Cooper MS, Keller RE. Perpendicular orientation and directional migration of amphibian neural crest cells in DC electric fields. Proc Natl Acad Sci USA, 81: 160-164, 1985.

8. Cooper MS, Schliwa M. Electrical and ionic controls of tissue cell locomotion in DC electric fields. J. Neurosci Res, 13: 223-244, 1985.

9. Dwyer AF, Wickham GG. Direct current stimulation in spinal fusion. Med J Aust, 1: 73-75, 1974.

10. Erickson CA, Nuccitelli RL. Embryonic cell motility can be guided by physiological electric fields. J Cell Biol, 98: 296-307, 1984.

11. Friedenberg ZB, Kohanim M. The effect of direct current on bone. Surg Gynecol Obstet, 131: 894-899, 1970.

12. Friedenberg ZB, Andrews ET, Smolenski BI et al. Bone reaction to varying amounts of direct current, Surg Gynecol Obstet, 131: 894-899, 1970.

13. Friedenberg ZB, Harlow MC, Brighton CT. Healing of nonunion of medial malleolus by means of direct current: a case report. J Trauma, 11: 883-885, 1971.

14. Friedenberg ZB, Roberts PG, Didizian NH, Brighton CT. Stimulation of fracture healing by direct current in the rabbit fibula. J Bone Joint Surg, 53A: 1400-1408, 1971.

15. Goh JCH, Bose K, Kang YK, Nugroho B. Effects of electrical stimulation on biomechanical properties of fracture healing in rabbits. Clin Orthop, 233: 268-273, 1988.

16. Illingworth CM, Baker AT. Measurement of electrical currents emerging during the regeneration of amputated finger tips in children. Clin Phys Physiol Meas, 1: 87, 1980.

17. Lavine LS, Lustrin I, Shamos M, Moss ML. The influence of electric current on bone regeneration in vivo. Acta Orthop Scand, 42: 305-314, 1971.

18. Luther PW, Peng HB, Lin JC. Changes in cell shape and action distribution induced by constant electrical fields. Nature, 303: 61-64, 1985.

19. Nannmark U, Buch F, Albrektsson T. Vascular reactions during electrical stimulation. Vital microscopy of the hamster cheek pouch and the rabbit tibia. Acta Orthop Scand, 56: 52-56, 1985.

20. Nessler JP, Mass DP. Direct current electrical stimulation of tendon healing in vitro. Clinical Orthpedics, 217: 303 -308, 1985.

21. Orida N, Feldman JHD. Directional protrusive psudopodial activity and motility in macrophages induced by extracellular electric fields. Cell Motility, 2: 243-255, 1982.

22. Nucatelli R, Erickson Ca. Embryonic cell motility can be guided by physiologic electric fields. Exp Cell Res, 147: 195-201, 1983.

23. Pethig R, Kell DB. The passive electrical properties of biologic systems: their significance in physiology, biophysics, and biotechnology. Phys Med Biol, 32 (8): 933-970, 1987.

24. Sawyer PN, Suckling EE, Wesolowski SA. Effect of small electric currents on intravascular thrombosis in the visualized rat mesentery. Am J Physiol, 198: 1006-1010, 1960.

25. Schwan HP. Mechanisms responsible for electrical properties of tissues and cell suspension. Med Prog Technol, 19 (4): 163-165, 1993-94.

History | Clinical Outcomes | Scientific Basis