RESUMEN
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.
RESUMEN
Purpose: We compared 2 commercially available nerve conduits-the Axoguard Nerve Connector, made of porcine small intestine submucosa (SIS), and the NeuraGen Nerve Guide, made of cross-linked bovine type I collagen (Col)-using a rodent model at 4 weeks, specifically focusing on subchronic host responses to the implants. Methods: A unilateral 5-mm sciatic nerve defect was created in 18 male Lewis rats and was repaired with SIS or Col conduits. After 4 weeks, histological evaluations of morphology, collagen content, macrophage polarization, vascularization, axonal regeneration, and myelination were conducted. To achieve a blinded examination, an independent qualified pathologist evaluated the images that were stained with hematoxylin-eosin, α-smooth muscle actin, and Masson trichrome stains. Results: The results showed a dominant macrophage type 2 (M2) response in the SIS group and a dominant macrophage type 1 (M1) response in the Col group. The SIS group showed deeper implant vascularization and fibroblast ingrowth than the Col group. Collagen deposition was higher within the lumen of the Col group than the SIS group. All Col conduits were surrounded by a colocalized staining of Masson trichrome and α-smooth muscle actin, forming a capsule-like structure. Conclusion: Distinctive histological features were identified for each conduit at the cellular level. The SIS conduits had a significantly higher number of host macrophages expressing M2 surface marker CD163, and the Col conduits showed a predominance of host macrophages expressing the M1 surface marker CD80. Data suggest that promoting the M2 response for tissue engineering and regenerative medicine is associated with a remodeling response. In addition, an independent analysis revealed an encapsulation-like appearance around all Col conduits, which is similar to what is seen in breast implant capsules. Clinical relevance: The biomaterial choice for conduit material can play an important role in the host tissue response, with the potential to impact adverse events and patient outcomes.
