Combining growth factor releasing microspheres within aligned nanofibers enhances neurite outgrowth

Abstract

Current treatments for peripheral nerve injuries include autografts, the gold standard, and commercially available nerve growth conduits (NGCs). Autografts have several drawbacks including donor site morbidity and nerve size mismatch, which lead to incomplete recovery. However, even with these drawbacks, autografts work better then commercially available NGCs that lack sufficient cues to promote complete regeneration. This study evaluated a combination of biomaterial components that can be added to the hollow internal space of a NGC to promote and direct nerve regeneration; specifically, mechanical, chemical, and topographical cues. Methacrylated hyaluronic acid (MeHA, mechanical cue) is electrospun into aligned fibers (topographical cue), with poly-lactic-co-glycolic acid microspheres to deliver nerve growth factor (NGF, chemical cue). The properties of the scaffold were evaluated under physiological conditions using environmental scanning electron microscopy and mechanical testing. The resulting scaffolds have hydrated porosities of 35-55% and Young's modulus in the range of 0.43-2.86 MPa. Enzyme-linked immunosorbent assay showed that NGF is released from the microspheres for up to 4 weeks. Dorsal root ganglia (DRG) neurons showed that the released NGF is bioactive. DRG testing on the scaffolds also showed that the combination of NGF released from the microspheres and the aligned nanofibers significantly enhanced neurite outgrowth. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 17-25, 2018.

Keywords: electrospinning; hyaluronic acid; microspheres; nerve growth conduit; peripheral nerve injury.