Accuracy of Motor Axon Regeneration Across Autograft, Single-Lumen, and Multichannel Poly(lactic-Co-Glycolic Acid) Nerve Tubes

Abstract

Objective Accuracy of motor axon regeneration becomes an important issue in the development of a nerve tube for motor nerve repair. Dispersion of regeneration across the nerve tube may lead to misdirection and polyinnervation. In this study, we present a series of methods to investigate the accuracy of regeneration, which we used to compare regeneration across autografts and single lumen poly(lactic-co-glycolic acid) (PLGA) nerve tubes. We also present the concept of the multichannel nerve tube that may limit dispersion by separately guiding groups of regenerating axons. Methods Simultaneous tracing of the tibial and peroneal nerves with fast blue (FB) and diamidino yellow (DY), 8 weeks after repair of a 1-cm nerve gap in the rat sciatic nerve, was performed to determine the percentage of double-projecting motoneurons. Sequential tracing of the peroneal nerve with DY 1 week before and FB 8 weeks after repair was performed to determine the percentage of correctly directed peroneal motoneurons. Results In the cases in which there was successful regeneration across single lumen nerve tubes, more motoneurons had double projections to both the tibial and peroneal nerve branches after single lumen nerve tube repair (21.4%) than after autograft repair (5.9%). After multichannel nerve tube repair, this percentage was slightly reduced (16.9%), although not significantly. The direction of regeneration was nonspecific after all types of repair. Conclusion Retrograde tracing techniques provide new insights into the process of regeneration across nerve tubes. The methods and data presented in this study can be used as a basis in the development of a nerve tube for motor nerve repair.

Controlling dispersion of axonal regeneration using a multichannel collagen nerve conduit

“…In the second experimental group, after sixteen weeks, all animals were anesthetized for simultaneous retrograde tracing [16]. The nerve graft and distal tibial and peroneal nerve branches were exposed.…”

“…Multichannel conduits, fabricated from poly(lactide-co-glycolide), showed promise for directed nerve growth over short observation times (six weeks) and limited gap size (7 mm) [14]; however, swelling has been shown in in vitro and in vivo studies to close the conduit cavities and block axonal growth over long-term study (twelve weeks) and larger gap sizes (10 mm) [15,16]. The precise function of multichannel on limiting dispersion compared with single channel nerve tubes has not been explored due to the dimensional instability of the synthetic polymer [16]. A multichannel nerve conduit with structural stability and favorable material and mechanical properties is needed to provide a reliable platform from which to investigate this mechanism.…”

Advances in Nerve Guidance Conduit-Based Therapeutics for Peripheral Nerve Repair

“…For example, molding of tubular constructs with shapes and macroscale patterns led to the development multichannel designs. This involves creating a defined number of channels within the luminal space of tubular constructs to control axonal target reinnervation 69 . The number of channels has been shown to influence successful repair of rat sciatic nerve defects, with 1 and 4-channel molded collagen-based tubular constructs both supporting excellent axonal regeneration, while only 4-channel tubular constructs were capable of promoting enhanced target reinnervation 70 .…”

Misdirection and guidance of regenerating axons after experimental nerve injury and repair

“…66 We have shown, for example (using the simultaneous tracing technique described above) that 8 weeks after repair of a 1-cm gap of the rat sciatic nerve with a single-lumen poly(lactic-coglycolic acid) nerve tube, 21.4% of the motoneurons had projections to both the tibial and peroneal nerve branch, compared with 5.9% after autograft repair. 15 This difference may be par- tially explained by the difference in the degree of axonal branching, but also by more dispersed regeneration of axonal branches in single-lumen nerve tube repair compared with contained regeneration of axonal branches inside the basal lamina tubes in autograft repair. Our hypothesis was that introduction of multiple channels inside the nerve conduit would decrease the percentage of axonal dispersion (Fig.…”