Electrospun PCL Nerve Conduit Filled with GelMA Gel for CNTF and IGF-1 Delivery in Promoting Sciatic Nerve Regeneration in Rat.

ABSTRACT

Neural tissue engineering is an essential strategy to repair long-segment peripheral nerve defects. Modification of the nerve conduit is an effective way to improve the local microenvironment of the injury site and facilitate nerve regeneration. However, the concurrent release of multiple growth cues that regulate the activity of Schwann cells and neurons remains a challenge. The present study involved the fabrication of a composite hydrogel, specifically methacrylate-anhydride gelatin-ciliary neurotrophic factor/insulin-like growth factor-1 (GelMA-CNTF/IGF-1), with the aim of providing a sustained release of CNTF and IGF-1. The GelMA-CNTF/IGF-1 hydrogels exhibited a swelling rate of 10.2% following a 24 h incubation in vitro. In vitro, GelMA hydrogels demonstrated a high degree of efficiency in the sustained release of CNTF and IGF-1 proteins, with a release rate of 85.9% for CNTF and 90.9% for IGF-1 shown at day 28. In addition, the GelMA-CNTF/IGF-1 composite hydrogel promoted the proliferation of Schwann cells and the production of nerve growth factor (NGF), connective tissue growth factor (CTGF), fibronectin, and laminin and also considerably promoted the axonal growth of neurons. Furthermore, GelMA-CNTF/IGF-1 hydrogels were loaded into PCL electrospun nerve conduits to repair 15 mm sciatic nerve defects in rats. In vivo studies indicated that PCL-GelMA-CNTF/IGF-1 could efficiently accelerate the regeneration of the rat sciatic nerve, promote the formation of the myelin sheath of new axons, promote the electrophysiological function of regenerated nerves, and eventually improve the recovery of motor function in rats. Overall, the PCL-GelMA-CNTF/IGF-1 scaffold presents an attractive new approach for generating an optimal therapeutic alternative for peripheral nerve restoration.