Mechanisms of Myofibroblast Activity and Phenotypic Modulation

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.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.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.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.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.