Long-term implantation

Parylene s use in the medical field is linked to electronics. Certain pacemaker manufacturers use it as a protective conformal coating on pacemaker circuitry (69). The coated circuitry is sealed in a metal can, so that the parylene coating serves only as a backup should the primary barrier leak. There is also interest in its use as an electrode insulation in the fabrication of miniature electrodes for long-term implantation to record or to stimulate neurons in the central or peripheral nervous system, as the "front end" of experimental neural prostheses (70). One report describes the 3-yr survival of functioning parylene-coated electrodes in the brain of a monkey (71). 

Pinchuk, L. et al. Polyisobutylene-Based Thermoplastic Elastomers for Ultra Long-Term Implant Applications, 6th World Biomaterials Congress Transactions, 2001, 1452. 

Some earlier developments and applications of various implantable pH sensors or measurement systems have been reported [128, 129, 130, 131]. However, reliable pH sensors for long-term implantations are still not available, and widespread clinical usage of implantable pH sensors has not been reached. Similar to other implantable sensors, the development of implantable pH microelectrodes, either fully implanted in the body or needle type sensors applied through the skin (percutaneous), has faced serious obstacles including sensor stability deterioration, corrosion, and adverse body reactions [48, 132, 133], Among them, encapsulation to prevent corrosion represents a major challenge for the implantable sensor devices [51]. Failure of encapsulation can cause corrosion damage on internal components, substrate materials, and electrical contacts [48], The dissolution of very thin pH sensitive layers will also limit the stability and lifetime of implantable micro pH sensors. 

The corrosion of antimony electrodes was also measured using ICP-MS (inductively coupled plasma mass spectrometry) for dissolved antimony in vivo [156], After the electrodes were inserted in the plasma, the antimony concentration showed a linear rise with time at a rate approximately of 94 j,g/L/h (r2 = 0.997). Although the projected antimony concentration is lower than the safe limit, accumulation of dissolved antimony and localized toxic effects in tissue may prevent the antimony electrode from long-term implantable applications. 

The easiness of elution of these compounds into the bloodstream does not permit an unambiguous interpretation of the obtained results. For this very reason there is actually no hope for successful long-term implantation of polymeric materials modified in this way. 

Invasive or surgical placement of a biomedical device produces tissue trauma, resulting in the formation of a wound site. Normal wounds heal and remodel over time to restore tissue homeostasis in the absence of implanted materials. Interestingly, sites of long-term implants do not heal properly the ensuing FBR prompted by the... 

So far decades of effort and large expenditures directed toward the development of a long-term implantable glucose sensor have failed to meet the expectations of medical researchers and the lay public. What should be apparent from this experience is that the complex foreign body reaction by the host dominates, and thus methodical, stepwise research using relevant and powerful in vivo model systems cannot be bypassed. This approach is virtually requisite if we are to ever have a clinically useful, subcutaneously implantable glucose sensor. 

Clarke error grid analysis of a study of 15 diabetic rats showed the percentage of readings that fell into the clinically correct regions (Zones A and B) increased from 92% to 96% when applying the Z-score rejection criteria.38 During the long-term implantation (25 4 days), Z-score calculations removed 32% of the individual sensor data from six fully implanted four-sensor arrays.39... 

For short-term applications, the host reaction to the foreign material should reach steady state rapidly and resist fouling during the duration of use. For long-term implantations, the steady-state immune response must be limited to minimal fibrous... 

The electrodes are manufactured from single or multistrand stainless steel wires (Fig. 4). The interconnection cables are coated with silicone. Besides a simple manufacturing technology, the electrodes demonstrate good electrical and mechanical properties [35]. In long term implantations the nerve damage due to continuous electrical stimulation was below 4.8%. Explantation of the electrodes is easy to perform [36]. 

The degradation of PCL in vivo is lower than that of PGA and PLA. Therefore, its use in long-term implantable devices has been studied. 

Carcinogenicity testing involves long-term implantation (up to 2 years) in an animal model usually under the skin to look for tumor formation (32). This test is required for devices... 

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