1.1. Background of the bion™Project

The basic form, function, and technology for the BION™ was identified by Dr. Gerald E. Loeb about the time that he joined the Bio-Medical Engineering Unit at Queen's University, Kingston, Ontario, Canada, in 1988. The principles underlying its manufacture stem from injectable transponder technology, now in widespread use for identifying pets and livestock, on which Dr. Loeb worked as a consultant in the 1980s. Disclosure of the concept for an injectable microstimulator to the Neural Prosthesis Program of the National Institutes of Health (National Institute of Neurological Disorders and Stroke) led to the first of a series of research contracts to the A.E. Mann Foundation for Scientific Research in Sylmar, California. The contracts provided funds to a triumvirate of research teams at the Mann Foundation (Joseph Schulman, Principal Investigator), Queen's University in Kingston, Ontario (Gerald Loeb and Frances Richmond, Principal Investigators), and the Illinois Institute of Technology in Chicago, Illinois (Philip Troyk, Principal Investigator), who have been developing and testing working models of the implantable microstimulator. More recently, these contracts have also included the development of bidirectional telemetry links that will eventually be used for complete functional neuromuscular control systems based on sensory feedback and command signals recorded from within the body. For the past five years, work at Queen's University has concentrated on fabrication of prototype microstimulators and preparation for clinical trials, including long term testing in animals and development of electronic hardware and computer software to permit therapists to create stimulation programs that therapists can administer in the clinic and study participants can administer later at home. This research has been funded by the Canadian Neuroscience Network of Centres of Excellence and by the Ontario Rehabilitation Technology Consortium.

Clinical trials that involve small groups of subjects are currently underway in Canada and in Italy (see discussion below). The study in Canada is intended to evaluate the safety and efficacy of intramuscular stimulation with BIONs™ to improve the strength, range of motion and, health of muscles and joints in the upper extremities of subacute stroke survivors. The aim of the study in Italy is to evaluate the safety and efficacy of neuromuscular stimulation delivered by BIONs™ for the treatment of quadriceps muscular hypotrophy in individuals with osteoarthritis. In the combined trials, a total of nine study participants have received BION™ treatment with no adverse effects.

1.2. Design Philosophy

The overall objective of this project is to provide a practical way to stimulate and exercise paralyzed muscles. In order to be practical, the technology must combine precise and reliable stimulation with ease and flexibility of use while minimizing costs and risks associated with implantation. The following three key factors dictated the unique design of the BION™ implants:

1. Size – One of the primary determinants of biocompatibility is the size of the implanted object. Both surface area and mass can affect the body’s response to nominally “biocompatible” materials. It was a primary design goal of this project to produce a modular implant that was as small as possible and which could operate without being linked physically by connectors and leads to a source of power or control.

2. Implantation – The method of implantation itself entails substantial risk of complications and morbidity, particularly if it entails invasive surgery in debilitated individuals. It was a primary design goal of this project to produce an implant with a form factor that permitted it to be implanted and reliably located by percutaneous injection rather than surgery.

3. Operation without leads – Perhaps the largest source of reliability problems in any electronic device arise from connectors and cables within and between devices. This is particularly so for implanted electronic devices which must survive constant motion while immersed in the saline fluids of the body. It was a primary design goal of this project to produce an implant that received data and power entirely by wireless means and that delivered its stimulation pulses via electrodes affixed rigidly to a rigid package.

2. PRIOR INVESTIGATIONS

Four aspects of investigation are important in evaluating the safety and efficacy of a medical device:

1. suitability of materials suggested by previous research and publications

2. biocompatibility as judged by in vitro and in vivo testing

3. safety and efficacy in animals

4. safety and efficacy in humans

2.1. Suitability of Materials

The BION™ implant is composed of electronic components contained in a borosilicate glass capsule sealed hermetically to tantalum and iridium electrodes at either end of the device.

2.1.1. Prior Research

The tantalum and iridium electrodes and the borosilicate glass capsule are the materials that are in direct contact with bodily fluids. The biocompatibility of these materials has been well documented in previous biocompatibility studies that have been reported in the literature.

6.1.TANTALUM (Ta)

2.1.1.1.1. Physicochemical Properties

Tantalum is a metal that is almost completely immune to chemical attack at temperatures below 150°C. It is degraded only by hydrofluoric acid, acidic solutions containing fluoride ions, and free sulfur trioxide.¹ Tantalum tested in Ringer’s solution and in a low pH solution (to mimic the environment of inflamed tissue), showed no significant reduction in its fatigue properties.² Further, tantalum is very resistant to corrosion. A semi- or non-conductive oxide layer forms spontaneously on the surface of tantalum which prevents any exchange of electrons and thus any redox reaction at the surface.^3,4,5 This ability to resist corrosion makes tantalum highly regarded for applications such as neuromuscular stimulation, in which pulses of current are delivered repetitively.

1. CRC Handbook of Chemistry and Physics (1981). R.C. Weast, ed. CRC Press, Inc. Boca Raton, Florida.

2. Weiss, B., Stickler, R., Schider, S., Schmidt, H. (1982) Corrosion fatigue testing of implant materials (Nb, Ta, stainless steel) at ultrasonic frequencies. In: Ultrasonic Fatigue: Proceedings of the First International Conference on Fatigue and Corrosion Fatigue up to Ultrasonic Frequencies. (pp. 387-411). Warrendale, PA: Metallurgical Society of AIME.

3. Evans, U.R. (1963). An Introduction to Metallic Corrosion. London: Edward Arnold Ltd.

4. Glantz, P., Bjorlin, G., & Sundstrom, B. (1975). Tissue reactions to some dental implant materials. Odont Review, 26, 231-238.

5. Sharma, C.P., & Paul, W. (1992). Protein interaction with tantalum: changes with oxide layer and hydroxyapatite at the interface. Journal of Biomedical Materials Research, 26, 1179-1184.