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Microparticles Releasing GDNF and NGF Improve Axonal Growth and Functional Recovery after Sciatic Nerve Injury in Rats
Amgad Hanna, MD1, Daniel Hellenbrand, BS2 and Clayton Haldeman, MD2, (1)Neurosurgery, University of Wisconsin, Madison, WI, (2)University of Wisconsin, Madison, WI

Introduction: Autologous nerve grafts and end-to-end neurorrhaphy are

considered the gold standard for large nerve gaps (i.e.>5 mm

gaps) for peripheral nerve injury repair. During nerve regeneration,

the local presence of growth factors plays an important role. In

order to aid in delivery of growth factors, we have modified

standard surgical micro-sutures with calcium phosphate (CaP)

coatings, which we have designed to deliver cytokines in a

temporally modulated manner, specifically GDNF (glial derived

neurotrophic factor) and NGF (nerve growth factor). In this study,

rat sciatic nerve injury is repaired with autograft with sutures

coated with GDNF and NGF with the goal of promoting more

axonal growth and improved functional outcomes compared to

control rats repaired with non-coated suture.

Methods: To create the injury, all rats had 6 mm of the right sciatic nerve

removed, and then a 10 mm isograft from a donor rat microsutured

end-to-end with two standard 9-0 Nylon sutures on the

proximal end and two sutures of the correct treatment on the distal

end. There were 5 groups (control, CaP only, GDNF, NGF, GDNF

+ NGF), each group consisted of 6-8 rats. Functional testing was

done weekly for each rat from week 5 to 12 post repair. The

experiment was terminated at 12 weeks and axonal growth was

assessed with electron microscopy

Results: Rats treated with MCM sutures coated with GDNF + NGF had

significantly increased (p=0.0014) axonal counts (mean: 8511) in

the sciatic nerve distal to neurorrhaphy compared to controls

(mean: 5123). Functional testing as measured by ankle

contracture, showed statistically significant improvement (p =

0.0014) starting at week 7 and continuing to week 12 compared to

control groups.

Conclusions: Mineral coated microparticle (MCM) sutures releasing GDNF

increase the amount of axons in the graft and distal to the graft.

MCMs releasing NGF and GDNF increase functional recovery

after week 7.

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