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In order to assess the usefulness of collagen and laminin gels prefilling nerve chambers to enhance nerve regeneration, we compared reinnervation of target organs after sciatic nerve resection leaving gaps of 4 or 6 mm followed by repair with silicone tubes in different groups of mice. Tubes were prefilled with saline solution, collagen gels, or laminin-containing gels at different concentrations. Functional reinnervation was assessed by noninvasive methods to quantitate recovery of sweating, nociceptive, sensory, and motor functions in the hindpaw repeatedly during 4-5 months postoperation. The increase in gap length between nerve stumps delayed the beginning and reduced the degree of functional recovery achieved. Reinnervation started earlier and achieved slightly higher levels with collagen gel diluted at 1.28 mg/ml than with more concentrated (1.92 and 2.56 mg/ml) collagen gels and with saline-prefilled tubes bridging a 4-mm gap. Recovery was also better with diluted (4 mg/ml) than with concentrated (12 mg/ml) laminin-containing gel, although lower than with collagen gels and saline. By prefilling silicone tubes bridging a 6-mm gap, a length considered limiting for regeneration in the mouse sciatic nerve, with diluted collagen or laminin gels, both matrices allowed for higher levels of recovery and for successful regeneration in a higher proportion of mice than saline solution. The laminin gel performed slightly better than the collagen gel.

This paper describes the use of a new polyimide sieve electrode as a chronic neural interface to stimulate and record signals from regenerated peripheral nerves. Flexible thin polyimide electrodes were placed in silicone chambers and implanted between the severed ends of the sciatic nerve in rats. The sieve part of the interface has 281 round via holes of 40 microns diameter, with seven integrated recording-stimulating electrodes arranged around via holes. Axonal regeneration through the via holes was demonstrated by histological and physiological methods over a two to six month post-implantation period in all the rats. The regenerated nerves were organized in fascicles corresponding to the grid pattern of the via holes. Longitudinal sections showed myelinated fibers, with normal appearance and well developed myelin sheath, crossing the via holes. Stimulation of the regenerated nerve through the polyimide electrode evoked distal muscle and nerve responses similar in amplitude to those evoked by nerve stimulation with hook metal electrodes. The polyimide electrodes were useful for recording nerve action potentials in response to electrical stimulation of the distal regenerated nerve, and in response to functional sensory stimulation of several modalities.

We compared reinnervation of target organs after sciatic nerve resection and repair by tubulization with biodurable tubes of silicone and teflon, or bioresorbable nerve guides of collagen and poly(L-lactide-co-6-caprolactone) (PLC) leaving a 6 mm gap in different groups of mice. All tubes were of 1 mm inside diameter and thin-walled (50 to 250 microm). Functional reinnervation was assessed by noninvasive methods to determine recovery of sweating, sensory and motor functions in the hindpaw repeatedly during 5 months postoperation. PLC guides allowed faster and higher levels of reinnervation for the four functions tested than collagen and silicone tubes, while teflon tubes gave the lowest levels of recovery. Regenerative reinnervation by thin nociceptive and sudomotor fibers was higher than by large sensory and alphamotor fibers in all groups. Resorbable tubes promoted regeneration in a higher proportion of mice than durable tubes. In cases with effective regeneration the nerve cable was multifascicular, with mild to moderate mononuclear cell infiltrates and a thin newly formed perineurium. The number of myelinated fibers was higher in PLC and silicone tubes than in collagen and teflon tubes. There was only minimal inflammatory reaction within the remnants of collagen tubes, but not in the other materials. PLC tubes of slow reabsorption rate seem useful for repairing long gaps in injured nerves.

This study evaluates the influence of aging on nerve regeneration and reinnervation of target organs in mice aged 2, 6, 9, 12, 18 and 24 months. In animals of each age group the sciatic nerve was subjected to crush, section or section and suture. Reinnervation of plantar muscles and sweat glands (SG) was evaluated over three months after operation by functional methods. Reappearance of SG secretion and motor responses occurred slightly earlier in young than older mice. The degree of motor and sudomotor reinnervation, with respect to preoperative control values, was also significantly higher in young than old animals. The differences were more pronounced after 12 months of age. The degree of recovery progressively decreased with the severity of the lesion, differences being more marked in older mice. Neurorraphy improved recovery, comparatively more in older than in young mice. These results indicate that, after injuries of peripheral nerves, axonal regeneration and reinnervation are maintained throughout life, but tend to be more delayed and slightly less effective with aging.

Functional reinnervation of sweat glands (SGs), skin, and muscle in the mouse paw after sciatic nerve lesions was evaluated to allow comparisons of the regeneration efficiency of different functional types of nerve fibers. In four groups of mice the sciatic nerve was crushed, sectioned, and left unrepaired or repaired by suture or tubulization. Reappearance of SG secretion and pinprick responses occurred slightly earlier than recordings of compound muscle and nerve action potentials in all groups. The degree of reinnervation, with respect to preoperative control values, of SGs and skin nociceptors was higher than the amplitude of the action potentials, mainly when the nerve injury was severe. The chances for recovery progressively decreased with the severity of the lesion, affecting the larger nerve fibers most. These results indicate that, after injuries of peripheral nerves, all types of nerve fibers are able to regenerate in the mouse, although small size fibers (sudomotor and nociceptive) allow for a higher degree of functional recovery than large myelinated fibers (skeletomotor and sensory).