Preclinical testing of Neural Prostheses

The development of neural stimulators: a review of preclinical safety and efficacy studies

“…Key aspects of the preclinical research are typically performed by an academic interdisciplinary research team with the relevant expertise. There are, however, additional preclinical studies that are generic and have been clearly defined in the International Organization for Standardization (ISO) document 10993–1 “Biological evaluation of medical devices” covering general biocompatibility testing of a device (24, 25), and ISO 14708 “Active Implantable Medical Devices” covering the evaluation of a device for mechanical and electrical integrity. This work is typically performed by experienced commercial research organizations after the final design specifications have been locked in and will be briefly described in section 8.…”

“…In vitro studies are often performed under conditions of accelerated aging including the use of elevated temperatures, harsh electrolyte environments and accelerated mechanical testing (25, 32, 49). For example, there is an approximate doubling of reaction rates for every 10°C increase in temperature based on the Arrhenius equation (25). These tests are generally performed at an early stage in the evaluation of a device, providing a mechanism for screening prior to chronic in vivo studies.…”

“…These tests are generally performed at an early stage in the evaluation of a device, providing a mechanism for screening prior to chronic in vivo studies. Some in vitro studies can be readily extended for long periods of time (years) to provide estimates of a device’s lifetime (25, 43, 53).…”

“…Chronic preclinical studies should be designed to address the mechanical and electrical integrity of the implant (abiotic) while in the same animal addressing the effect of the implant on its biological environment (biotic, Fig. 2; (25, 32, 55)). Abiotic failure includes loss of optimal device function including high impedance electrodes, low impedance cable crosstalk, delamination or corrosion of electrode contacts, or delamination of insulation.…”

“…These effects are most critical in devices associated with significant movement resulting in abrasion of the insulation (120), and in small implants where insulation is by necessity very thin (19). Because the lifetime of many insulating films are adversely affected by the electric field strength, evaluating the efficacy of new insulating materials should be performed under electrically active conditions (25, 43, 142).…”