Artificial dural sealant that allows multiple penetrations of implantable brain probes

Abstract

This study reports extensive characterization of the silicone gel (3-4680, Dow Corning, Midland, MI), for potential use as an artificial dural sealant in long-term electrophysiological experiments in neurophysiology. Dural sealants are important to preserve the integrity of the intracranial space after a craniotomy and in prolonging the lifetime and functionality of implanted brain probes. In this study, we report results of our tests on a commercially available silicone gel with unique properties that make it an ideal dural substitute. The substitute is transparent, elastic, easy to apply, and has re-sealing capabilities, which makes it desirable for applications where multiple penetrations by the brain probe is desirable over an extended period of time. Cytotoxicity tests (for up to 10 days) with fibroblasts and in vivo tests (for 12 weeks) show that the gel is non-toxic and does not produce any significant neuronal degeneration when applied to the rodent cortex even after 12 weeks. In vivo humidity testing showed no sign of CSF leakage for up to 6 weeks. The gel also allows silicon microprobes to penetrate with forces less than 0.5 mN, and a 200-microm diameter stainless steel microprobe with a blunt tip to penetrate with a force less than 2.5 mN. The force dependency on the velocity of penetration and thickness of the gel was also quantified and empirically modeled. The above results demonstrate that the silicone gel (3-4680) can be a viable dural substitute in long-term electrophysiology of the brain.

Figure 1

Micrograph of the silicone gel on a rodent brain after the dura was incised and removed.

Figure 2

Results of cytotoxicity tests using mouse fibroblasts (3T3) show (left) cells in a standard well after 3 days in a control experiment, (middle) cells seeded on a 1:1 volume ratio of part A to part B composition of the gel after 3 days (right) live-dead cell assay of cells seeded on the gel where green represents live cells after 10 days.

Figure 3

Histology (silver stain) results from in vivo tests of the gel after 12 weeks in adult rodent brains are shown. In (a) a coronal section showing both sides of the brain where the silicone gel was applied on right side and the gelfoam on the left show no significant differences between the silver stains of either side and negligible neuronal degeneration. The scale bar represents 1 mm. In (b) a close-up of the control or gel foam side is shown and in (c) a close up of the silicone gel side is shown indicating no significant neuronal degeneration in either side and no significant differences between the two sides. Magnification in (b) and (c) was 40X.

Figure 4

Force measurement plots, showing the force to penetrate the gel and the force to extract the electrodes at (a) different volume compositions of the gel (b) different penetration velocities of the probe and (c) different thicknesses of the gel. Red bars represent data for the 200-μm diameter stainless steel probe (SS), blue bars represent data for the silicon probe (SP) and error bars represent±1 S.D.

Figure 5

Results of humidity tests to assess the sealing capabilities of gel are shown. Four traces showing in vivo humidity levels and room humidity levels. Device 1, humidity was measured for 3 weeks, where device 2 was measured for 6 weeks. No CSF leakage was seen in either device.