- •1.1. Background of the bion™Project
- •1.2. Design Philosophy
- •2.1.1.1.2. Electrochemical Characteristics
- •2.1.1.1.3. Biocompatibility
- •2.1.1.1.4. The Use of Tantalum in Medical Applications
- •2.1.1.1.5. Surface Characteristics and Biocompatibility of Tantalum
- •6.2.Iridium (Ir)
- •6.2.1.1.Physical/Chemical properties
- •6.3.Borosilicate glass
- •2.2. Biocompatibility as judged by in vitro and in vivo testing
- •2.2.1. Published Pre-Clinical Research
- •6.2.1.2.Use of Iridium in Medical Applications
- •2.2.2. Unpublished Pre-clinical Studies
- •6.4.In Vitro Tests
- •6.4.1. Salmonella Typhimurium Reverse Mutation Test
- •6.4.2.Chromosomal Aberration Test
- •6.4.3. Sister Chromatid Exchange
- •2.2.2.1.4. Cytotoxicity Testing in the l-929 Mouse Fibroblast Cell Line
- •6.5.Short Term in vivo Tests
- •6.5.1. Intracutaneous Reactivity Study in the Rabbit
- •6.5.2. Acute Systemic Toxicity Study in the Mouse
- •6.5.3. Sensitization Study in the Guinea Pig (Maximization Method)
- •6.6.Long-term In Vivo Tests
- •2.3. Safety and Efficacy in Animals
- •2.3.1. Electromagnetic Compatibility
- •2.3.2. Stress Tests
- •6.7.Three-Point Bending Test
- •6.8.Impact Testing
- •2.4. Safety and Efficacy in Humans
- •2.4.1. Electrical Stimulation Using bioNs™ to Treat Shoulder Subluxation Soon After Stroke
- •6.9.Background
- •6.10.Trial Description
- •6.11.Preliminary Results
- •2.4.2. Electrical Stimualtion Using bioNs™ To Treat Muscular Hypotrophy In Individuals With Osteoarthritis
- •6.12. Background
- •6.13.Trial Description
- •6.14.Preliminary Results
- •2.5. Adverse information
- •7.Investigational plan
2.1.1.1.2. Electrochemical Characteristics
The following references examine the electrochemical characteristics of tantalum electrodes and assess the use of tantalum in chronic stimulation. They show that the particular form of anodized, sintered tantalum used in the BION™ implants is a safe and effective electrode for long-term stimulation of tissue and that it effectively prevents the passage of direct current which can cause tissue damage of the kind that can be provoked with other types of electrodes.
1. Bernstein, J.J., Hench, L.L., Johnson, P.F., Dawson, W.W., & Hunter, G. (1977). Electrical stimulation of the cortex with tantalum pentoxide capacitive electrodes. In F.T. Hambrecht & I.B. Reswick (Eds.), Functional Electrical Stimulation: Applications in Neural Prostheses. (pp. 465-477). New York: Marcel Dekker .
2. Guyton, D.L., & Hambrecht, F.T. (1973). Capacitor electrode stimulates nerve or muscle without oxidation-reduction. Science, 181, 74-76.
3. Guyton, D.L., & Hambrecht, F.T. (1996). Theory and design of capacitor electrodes for chronic stimulation. Medical and Biological Engineering, 12, 613-619.
4. Johnson, P.F., Bernstein, J.I., Hunter, D.W., Dawson, W.W., & Hench, L.L. (1977). An in vitro and in vivo analysis of anodized tantalum capacitive electrodes: Corrosion response, physiology, and histology. Journal of Biomaterials Research,11, 637-656.
5. Rose, T.L., Kelliher, E.M., & Robblee, L.S. (1985). Assessment of capacitor electrodes for intracortical neural stimulation. Journal of Neuroscience Methods, 12, 181-193.
6. Schmidt, E.M., Hambrecht, F .T., & McIntosh, I.S. (1982). Intracortical capacitor electrodes: Preliminary evaluation. Journal of Neuroscience Methods, 5, 33-39.
2.1.1.1.3. Biocompatibility
A broad range of experiments has been performed to test the biocompatibility of tantalum in various tissue types. Different forms of tantalum have been implanted into numerous target tissues with little or no adverse tissue reaction. The following animal studies examined the effects of tantalum on various tissue types:
1. Fontaine, A.B., Dake, M.D., Tschang, T., Stabbe, M.T., & Dos Passos, S. (1993). Tantalum balloon-expandable stent: in vivo swine studies. Journal of Vascular Interventional Radiology, 4, 749-752.
2. Scott, N.A., Robinson, K.A., Nunes, G.L., Thomas, C.N., Viel, K., King, S.B., Harker, L.A., Rowland, S.M., Luman, I., & Cipolla, G.D. (1995). Comparison of the thrombogenicity of stainless steel and tantalum coronary stents. American Heart Journal, 129(5), 866-72.
3. Samuels, P.B., Roedling, H., Katz, R., & Cincotti, J.I. (1966). A new hemostatic clip: 2-year review of 1007 cases. Annals of Surgery, 163, 427.
4. Robinson, I.D., Yedlicka, I. W., Bildsoe, M.C., Vlodaver, Z., Hunter, D. W., Castaneda-Zuniga, W ., & Amplatz, K. (1990). The biocompatibility of compressed collagen foam plugs. Cardiovascular and Interventional Radiology, 13, 36-39.
5. Nadel, J.A., Wolfe, W.G., & Graf, P.D. (1968). Powdered tantalum as a medium for bronchography in canine and human lungs. Investigative Radiology, 3, 229.
6. Aronson, A.S., Ionsson, N., & Alberius, P. (1985). Tantalum markers in radiography. Skeletal Radiology, 14, 207 -211.
7. Alberius, P. (1998). Bone reactions to tantalum markers. A scanning electronic microscope study. Acta Anatomica (Basel), 115, 310.
8. Michel, R., Reich, M., Notle, M., Rabenseifner, L., Horn, E.M., & Holm, R. (1988). INAA of rabbit tissues and organs after application of tantalum implants. Trace Element Analytical Chemistry in Medicine and Biology, 504-512.
9. von HoIst, H., Collins, P ., & Steiner, L. (1981 ). Titanium, Silver, and Tantalum Clips in brain tissue. Acta Neurochirurgica, 56,239-242.
10. Cardella, J.F., Wilson, R.P., Fox, P.S., & Griffith, J.W. (1995). Evaluation of a second-generation tantalum biliary stent in a canine model. Journal of Vascular & Interventional Radiology, 6, 397-403.
11. Bosnjakovic, P., Ilic, M., Ivkovic, T., Kutlesic, C., Mihailovic, D., Savic, V., & Petkovic, B. (1994). Flexible tantalum stents: effects in the stenotic urethra. Cardiovascular and Interventional Radiology, 17, 280-284.