Dual Functional Collagen Nerve Conduits for Bridging Critical Nerve Gaps

Aim: Peripheral nerve injuries affect more than one million people each year and often result in lifelong disabilities. Currently available treatment options are associated with several drawbacks. For addressing some of these problems, we have developed dual functional collagen nerve conduits (C-NCs) for triggering axonal regeneration in a rabbit sciatic nerve gap (˃40 mm) model. Dual functionality consisted in an embedded growth factor [GDNF] and aligned microfibers in the C-NC. Methods: GDNF, a potent growth factor (GF) for motor neurons, was engineered with collagen binding domain (CBD-GDNF) and expressed in eukaryotic cells. Resulting recombinant GF was loaded into C-NCs reinforced with aligned PLGA microfibers. As a control, unmodified GDNF was loaded into C-NCs. In vitro release kinetics was studied over 28 days followed by bioactivity assay of the released GF. Subsequently, biological performance of dual functional NC was tested in vitro using chicken embryonic motor neurons. Bioactive C-NC was further optimized for testing their biological performance in a rabbit sciatic nerve gap model. In the line of establishing this model, perfusion-fixed rabbit lower limbs were used for anatomical evaluation. Surgical procedures were reviewed and key requirements were identified.