Comparison of acellular nerve allograft modification with Schwann cells or VEGF.
BACKGROUND
Individual contributions of exogenous Schwann cells (SCs) and vascular endothelial growth factor (VEGF) were evaluated in acellular nerve allografts (ANAs). ANA processing removes SCs and vasculature, likely contributing to reduced regeneration compared to autografts. Exogenous SCs may improve the regenerative microenvironment, and VEGF has been shown to stimulate angiogenesis. Replacing these components in ANAs may improve regeneration.


METHODS
A rat sciatic nerve transection model was used to study 20-mm grafts. Four graft types were studied: (1) isograft, (2) ANA, (3) ANA-SCs, and (4) ANA-VEGF. After 10 weeks in vivo, the midgraft and distal nerve to the grafts were analyzed for axonal regeneration using histomorphometry to assess total myelinated axon counts, density, width, and percent neural tissue.


RESULTS
The most axons in the distal nerve were regenerated in the isograft followed by the ANA- SC group, with 9171 ± 1822 and 7103 ± 1576 regenerated axons respectively. Both the ANA and ANA-VEGF groups had significantly fewer regenerated axons compared to the isograft (p < 0.05) with 5225 ± 2994 and 5709 ± 2657 regenerated axons, respectively. The ANA and ANA-VEGF groups also had significantly reduced fiber density and percent nerve compared to the isograft; the isograft and ANA-SC groups were not significantly different (p < 0.05).


CONCLUSIONS
These results show that SCs improve axonal regeneration in a 20 mm ANA to a greater extent than VEGF. VEGF treatment showed a trend toward increased axonal regeneration but was not significantly different compared to the untreated ANA. The role of VEGF may be clearer in longer grafts where ischemia is a greater factor.
Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, Campus Box 8238, 660 South Euclid Avenue, St. Louis, MO 63110 USA.
Gwendolyn
G
Hoben
Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, Campus Box 8238, 660 South Euclid Avenue, St. Louis, MO 63110 USA.
Ying
Y
Yan
Department of Biomedical Engineering, Washington University, Campus Box 1097, One Brookings Drive, St. Louis, MO 63130 USA.
Nisha
N
Iyer
Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, Campus Box 8238, 660 South Euclid Avenue, St. Louis, MO 63110 USA.
Piyaraj
P
Newton
Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, Campus Box 8238, 660 South Euclid Avenue, St. Louis, MO 63110 USA.
Dan A
DA
Hunter
Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, Campus Box 8238, 660 South Euclid Avenue, St. Louis, MO 63110 USA.
Amy M
AM
Moore
Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, Campus Box 8238, 660 South Euclid Avenue, St. Louis, MO 63110 USA ; Department of Biomedical Engineering, Washington University, Campus Box 1097, One Brookings Drive, St. Louis, MO 63130 USA.
Shelly E
SE
Sakiyama-Elbert
Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, Campus Box 8238, 660 South Euclid Avenue, St. Louis, MO 63110 USA.
Matthew D
MD
Wood
Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, Campus Box 8238, 660 South Euclid Avenue, St. Louis, MO 63110 USA.
Susan E
SE
Mackinnon
Nerve allografts; Nerve grafts; Nerve regeneration; Peripheral nerve; Schwann cell; VEGF; Vascular endothelial growth factor