Silicone rubber multiple-lumen nerve cuffs were used to compare the effectiveness of two varieties of nerve growth stimulants (collagen and a mixture of collagen, fibronectin, and laminin) at the same time for regenerating cables across the same gap. The right sciatic nerve was transected in adult Sprague-Dawley rats. The proximal and distal stumps were inserted each into an end of the single lumen portion of a multiple-lumen cuff in which different chemical fillings were used in 6 tubes of the multiple lumen portion of the cuff. The filling pattern alternated with collagen gel or with a gel mixture of collagen, laminin, and fibronectin. A 15 mm gap was then created between stumps in ten animals. After 8 weeks implantation period, 53% (32 of 60) of the lumens displayed successful cable regeneration across the 15 mm gaps in the animals implanted with the multiple-lumen cuffs (each gap conduit diameter = 0.5 mm) for both material fillings;Regenerates had an organized cellular matrix. Features that resembled axonal profiles (regeneration units) were seen in six proximal cable sections, three from the mixture-filled lumen and three from the collagen-filled lumen. These axonal profiles were restricted to proximal sections and were not seen in the middle and distal sections for both chemical environments for this 8 week implantation period. Schwann cells were consistently observed in the core of the majority of cables. Blood vessels were common in proximal and distal cable sections and were seldom seen in the middle cable sections. No blood vessels were observed in the middle cable sections from the collagen-filled lumens. Several layers of concentrically arranged tissue containing fibroblasts were observed in the form of epineurial rims for cables formed in both chemical environments. Acellular material associated with the gel or the fibrin matrix within the lumens was seen in the cores of the cables from both environments. However, the cores of cables from the mixture-filled lumens had relatively small acellular region fractions as compared to those from the collagen-filled lumens when area data were normalized using an acellular area of core to total area of core ratio for comparison for the two environments (collagen versus mixture), especially for sections in the middle regions (p = 0.003). The stimulation of a microenvironment offered by the mixture of laminin, fibronectin, and collagen provided a more advanced development for regenerating cables compared to collagen lumen fillings.