* Corresponding author. Tel.: #49-511-532-2895; fax: #49-511- 532-2880. E-mail address: wewetzer.konstantin@mh-hannover.de (K. Wewetzer). Biomaterials 22 (2001) 2333}2343 Immunohistochemical characterization of axonal sprouting and reactive tissue changes after long-term implantation of a polyimide sieve electrode to the transected adult rat sciatic nerve Petra Margarete Klinge, Morad Ali Vafa, Thomas Brinker, Almuth Brandis, Gerhard Franz Walter, Thomas Stieglitz, Madjid Samii, Konstantin Wewetzer* Department of Neurosurgery, Hannover Medical School, 30625 Hannover, Germany Department of Neurosurgery, Nordstadt Hospital Hannover, 30167 Hannover, Germany Department of Neuropathology, Hannover Medical School, 30625 Hannover, Germany Fraunhofer Institute for Biomedical Engineering, Ensheimer Str. 48, 66386 St. Ingbert, Germany Department of Neuroanatomy, Hannover Medical School, Center of Anatomy OE4140, Carl-Neuberg-Str 1, 30625 Hannover, Germany Received 11 September 2000; accepted 27 November 2000 Abstract The development of arti"cial microstructures suited for interfacing of peripheral nerves is not only relevant for basic neur- ophysiological research but also for future prosthetic approaches. Aim of the present study was to provide a detailed analysis of axonal sprouting and reactive tissue changes after implantation of a #exible sieve electrode to the proximal stump of the adult rat sciatic nerve. We report here that massive neurite growth after implantation, steadily increasing over a period of 11 months, was observed. Parallel to this increase was the expression of myelin markers like Po, whereas non-myelin-forming Schwann cells did not change. Compared to "ve weeks post-implantation, where both Schwann-cell phenotypes were intermingled with each other, non-myelin-forming Schwann cells occupied a peripheral position in each microfascicle after 11 months. After an initial increase, hematogenous macrophages were down-regulated in number but maintained close contact with the implant. However, at no time were signs of its degradation observed. It is concluded that the introduced #exible polyimide electrode is suitable for contacting peripheral nerves since it permits substantial neurite growth and o!ers excellent long-term stability.  2001 Elsevier Science Ltd. All rights reserved. Keywords: Biocompatibility; Sieve electrode; Polyimide; Axonal sprouting; Sciatic nerve 1. Introduction The peripheral nervous system is generally considered a permissive environment with respect to neurite growth after injury [1,2]. Complete functional recovery in the clinical practice, however, is only observed, when nerves are severed at some distance away from the cell body. Proximal lesions, like those of the brachial plexus, still have a poor clinical prognosis [3}6]. This is due, at least in part, to the irreversible destruction of muscle tissue during the prolonged time interval in which regenerating neurites regrow towards their target tissue [1,7}9]. One experimental strategy to improve recovery after such lesions is to restore the neuromuscular junction by graft- ing of embryonic spinal cord and/or cortical neurons into the spinal cord or the distal part of the transected peri- pheral nerve [10}14]. The atrophy of muscle, however, will only be e$ciently counteracted when the neuromus- cular junction regains controlled activity. Putting such experimental approaches into practice will therefore not only require the grafting of neurons but also their electri- cal stimulation triggering muscle contraction. This may be achieved by electrodes integrated into the nerve. A number of groups have followed this approach of micromachined neural prostheses and a variety of 0142-9612/01/$- see front matter  2001 Elsevier Science Ltd. All rights reserved. PII:S0142-9612(00)00420-8