Histological Comparison of Porcine Small Intestine Submucosa and Bovine Type-I Collagen Conduit for Nerve Repair in a Rat Model

Purpose:After nerve injury, macrophages and Schwann cells remove axon and myelin debris. We hypothesized that nerves repaired with different conduit materials will result in varying levels of these cell populations, which impacts Wallerian degeneration and axonal regeneration. Methods:We performed a unilateral sciatic nerve transection in 18 rats. The nerves were repaired with small intestine submucosa (SIS, n = 9) or isolated type-I collagen (CLC, n = 9) conduits. Rats were monitored for 4 weeks. Histology samples were obtained from the proximal nerve, mid-implant, and distal nerve regions. Samples were stained for total macrophages, M2 macrophages, foamy phagocytes, Schwann cells, vascular components, axon components, and collagen density. Results:Distal nerve analyses showed higher populations of total macrophages and M2 macrophages in SIS-repaired nerves and higher density of foamy phagocytes in CLC-repaired nerves. Proximal nerve, mid-implant, and distal nerve analyses showed higher Schwann cell and vascular component densities in SIS-repaired nerves. Axon density was higher in the mid-implant region of SIS-repaired nerves. Collagen staining in the mid-implant was scant, but less collagen density was observed in SIS-repaired versus CLC-repaired nerves. Conclusions:In the distal nerve, the following were observed: (1) lower total macrophages in CLC-repaired nerves, suggesting lower overall inflammation versus SIS-repaired nerves; (2) higher M2 macrophages in SIS-repaired versus CLC-repaired nerves, a driving factor for higher total macrophages and indicative of an inflammation resolution response in SIS-repaired nerves; and (3) a lower foamy phagocyte density in SIS-repaired nerves, suggesting earlier resolution of Wallerian degeneration versus CLC-repaired nerves. In the proximal nerve, mid-implant, and distal nerve, higher Schwann cell and vascular component densities were noted in SIS-repaired nerves. In the mid-implant, a higher axon component density and a lower collagen density of the SIS-repaired nerves versus CLC-repaired nerves were noted. These results indicate more robust nerve regeneration with less collagen deposition. Clinical relevance:This in vivo study evaluated two common conduit materials that are used in peripheral nerve repair. Clinical outcomes of nerves repaired with conduits may be impacted by the response to different conduit materials. These nerve repair responses include Wallerian degeneration, nerve regeneration, and nerve scarring. This study evaluated Wallerian degeneration using total macrophages, M2 macrophages, and foamy phagocytes. Nerve regeneration was evaluated using Schwann cells and axons. Nerve scarring was evaluated using vascular and collagen density.