**7. Novel Technique**

A novel technique was tested clinically for bridging a nerve gap. It involved bridging a 12-cm-long ulnar nerve gap with a PRP-filled collagen tube [205]. The subject was a 58-year-old male, and the repair was performed post-nerve trauma (Figure 1). The subject recovered good motor and sensory function [205]. Thus, both sensory and motor function can be restored, even when simultaneously, all three nerve trauma values far exceeded those where sensory nerve grafts alone are effective. This result shows that functional recovery can be restored under conditions where sensory nerve grafts, allografts, and conduits are not effective. The technique is presently being further tested.

Support for the clinically observed efficacy of a PRP-filled collagen tube enhancing axon regeneration comes from both a clinical study and a number of animal studies. Clinically, the application of PRP eye drops to the cornea enhances the regeneration of sensory innervation [206]. PRP applied to the site of anastomosed rat nerve stumps enhances the extent of axon regeneration in rats [207–209] and guinea pigs, In rabbits, PRP applied to an autograft increases Schwann cell proliferation and the extent of axon regeneration [210]. Bridging a rat sciatic nerve gap with a PRP-filled silicon tube [198,211] or surrounding the sciatic nerve anastomosis site with a PRP-saturated membrane [212] enhances axon regeneration. In rabbits, filling vein grafts with PRP induces significant axon regeneration compared to empty vein grafts [198,206,213–215].

The influence of PRP in enhancing axon regeneration has been proposed to result from platelet-released neurotrophic and other factors [214–217]. An additional platelet potential contributor to enhanced axon regeneration is VEGF, which, as discussed earlier, induces enhanced axon regeneration by inducing rapid vascularization of the entire nerve gap [218,219]. This result suggests that platelet-released neurotrophic and other factors create an environment within the collagen tube that promotes axon regeneration despite a long nerve gap, a long delay between nerve trauma and repair, and an old patient. These results sugges<sup>t</sup> that the platelet-released factors play a number of roles to induce axon regeneration and functional recovery: (1) They induce neurons to extend axons long after they normally do not; (2) induce the Schwann cells of the proximal nerve stump to proliferate, and release axon regeneration-promoting factors; (3) induce the Schwann cells of the proximal stump to migrate with the elongating axons; (4) induce the Schwann cells of the distal nerve to proliferate and

release neurotrophic factors and support axon regeneration into and through the distal nerve to the denervated targets; (5) a platelet-released factor, potentially VEGF, promotes vascularization of the gap region.

**Figure 1.** Repairing an ulnar nerve with a 12-cm-long gap. (**A**) Sewing two 4 × 8 cm collagen sheets together end to end, and then into a 16-cm-long tube around the handle of a surgical tool. (**B**) The collagen tube cut to a 12.6 cm length and placed in the nerve gap. (**C**) The proximal and distal nerve stumps secured about 3 mm into the collagen tube. (**D**) Completed nerve gap repair with the collagen tube filled with autologous platelet-rich plasma (PRP).

Confirmation of this result will mean that, without sacrificing a sensory nerve function, neurological recovery can be restored under conditions of long nerve gaps, when repairs are performed years post-trauma and to older patients.
