Nerve implants with bioactive interfaces enhance neurite outgrowth and nerve regeneration in vivo

Abstract

Nerve implants functionalized with growth factors and stem cells are critical to promote neurite outgrowth, regulate neurodifferentiation, and facilitate nerve regeneration. In this study, human umbilical cord mesenchymal stem cells (hUCMSCs) and 3,4-hydroxyphenalyalanine (DOPA)-containing insulin-like growth factor 1 (DOPA-IGF-1) were simultaneously applied to enhance the bioactivity of poly(lactide-co-glycolide) (PLGA) substrates which will be potentially utilized as nerve implants. In vitro and in vivo evaluations indicated that hUCMSCs and DOPA-IGF-1 could synergistically regulate neurite outgrowth of PC12 cells, improve intravital recovery of motor functions, and promote conduction of nerve electrical signals in vivo. The enhanced functional and structural nerve regeneration of injured spinal cord might be mainly attributable to the synergistically enhanced biofunctionality of hUCMSCs and DOPA-IGF-1/PLGA on the bioactive interfaces. Findings from this study demonstrate the potential of hUCMSC-seeded, DOPA-IGF-1-modified PLGA implants as promising candidates for promoting axonal regeneration and motor functional recovery in spinal cord injury treatment.