Living axonal scaffolds for peripheral nerve regeneration. Survival and integration of implanted living tissue engineered nerve grafts (TENGs) at 6 weeks following transplantation to bridge excised segments of sciatic nerve in rats. Constructs consisted of longitudinally aligned axonal tracts (GFP+) generated based on axonal “stretch-growth.” (A) Longitudinal section of continuous proximal (top) and distal (bottom) nerve across the repair site (scale bars = 0.5 mm). Note multiple transplanted ganglia on the proximal and distal ends with aligned axonal tracts spanning those neuronal populations (GFP+). (B) Regenerating host axons (neurofilament; red) entered into the proximal end of the constructs and were not co-localized with GFP. (C) However, host axons (red) across the center of the grafts were co-localized with GFP+ transplanted axons, suggesting host regeneration occurred along the transplanted axonal tracts. (D) A subset of GFP+ TENGs were transplanted across the excised sciatic nerve in transgenic rats expressing alkaline phosphatase (AP; red). Here, neurites from transplanted neurons (GFP+, short arrow) were observed in intimate contact with axons from the host (AP+, arrow heads) and were often intertwined (long arrows). These observations suggested that host axonal regeneration occurred directly along the living scaffold of aligned axonal tracts presented by TENGs. Adapted with permission from [56].