- •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
- •6.2.1.2.Use of Iridium in Medical Applications
- •6.3.Borosilicate glass
- •2.2. Biocompatibility as judged by in vitro and in vivo testing
- •2.2.1. Published Pre-Clinical Research
- •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 Unpublished Pre-clinical Studies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
6.5.Short Term in vivo Tests
6.5.1. Intracutaneous Reactivity Study in the Rabbit
Irritation tests estimate the irritation potential of devices, materials and/or their extracts using an appropriate site for implantation. Intracutaneous toxicity tests will screen for the local toxicity of leachable materials.
Test Description
The BIONs were extracted in 0.9% Sodium Chloride USP solution and Cottonseed Oil, NF. These extracts were evaluated for the intracutaneous reactivity in accordance with the requirements of the International Organization of Standardization: Biological Evaluation of Medical Devices, Part 10: Tests for Irritation and Sensitization.
A 0.2 ml dose of extract was injected by the intracutaneous route into five separate sites on the right side of the back of each rabbit. Similarly, the corresponding reagent control was injected on the left side of the back of each rabbit. Three rabbits were used for each pair of extracts. The injection sites were observed immediately after injection. Observations for erythema and edema were conducted at 24, 48, and 72 hours after injection.
Test Results
Under the conditions of this study, there was no evidence of significant irritation or toxicity from the extracts injected intracutaneously into rabbits.
6.5.2. Acute Systemic Toxicity Study in the Mouse
Test Description
Test articles were extracted in 0.9% Sodium Chloride USP solution and Cottonseed Oil, NF. The extracts were evaluated for intracutaneous reactivity in accordance with the requirements for the International Organization of Standardization: ISO 10993 Biological Evaluation of Medical Devices, Part 11: Tests for Systemic Toxicity. A single dose of the appropriate extract was injected by the intracutaneous route into five mice per extract by either the intravenous or intraperitoneal route. Similarly, five mice were dosed with each corresponding reagent control. The animals were observed immediately and at 4, 24, 48, and 72 hours after systemic injection.
Test Results
Under the conditions of this study, there was no mortality or evidence of significant systemic toxicity from the extracts.
6.5.3. Sensitization Study in the Guinea Pig (Maximization Method)
Test Description
A guinea pig sensitization test was conducted in accordance with the requirements of the International Organization for Standardization, Part 10: ISO 10993 Tests for Irritation and Sensitization. Sensitization tests estimate the potential for contact sensitization as the result of exposure to the device, its materials or its extracts, by using an animal model. BIONs were extracted in 0.9% Sodium Chloride (USP) and Cottenseed Oil (NF). Each extract of the test article was injected intradermally and patched occlusively to ten test guinea pigs (per extract) in an attempt to elicit sensitization. Following a recovery period, the test and control animals received a challenge patch of the appropriate test article and control vehicle. All sites were scored at 24, 48 and 72 hours after patch removal.
Test Results
Under conditions of this study, neither saline nor cottenseed oil extracts showed evidence of causing delayed contact sensitization in the guinea pig.