Spatio-temporal release of NGF and GDNF from multi-layered nanofibrous bicomponent electrospun scaffolds

Chaoyu Liu,Min Wang,Feiyue Xu,Zongxian Li,Haibo Cong,Xiaohua Li,Yuan Song

doi:10.1007/s10856-018-6105-x

Abstract

Scaffolds capable of providing dual neurotrophic factor (NTF) delivery with different release kinetics, spatial delivery of NTFs at different loci and topographical guidance are promising for enhanced peripheral nerve regeneration. In this study, we have designed and fabricated multi-layered aligned-fiber scaffolds through combining emulsion electrospinning, sequential electrospinning and high-speed electrospinning (HS-ES) to modulate the release behavior of glial cell line-derived growth factor(GDNF) and nerve growth factor (NGF). GDNF and NGF were incorporated into poly(lactic-co-glycolic acid) (PLGA) fibers and poly(D,L-lactic acid) (PDLLA) fibers, respectively. Aligned fibers were obtained in each layer of multi-layered scaffolds and relatively thick tri-layered and tetra-layered scaffolds with controlled layer thickness were obtained. Their morphology, structure, properties, and the in vitro release of growth factors were examined. Dual and spatio-temporal release of GDNF and NGF with different release kinetics from multi-layered scaffolds was successfully demonstrated. High separation efficiency by PDLLA fibrous barrier layer for spatial neurotrophic factor delivery from both tri-layered scaffolds and tetra-layered scaffolds was achieved.

Highlights

Peripheral nerve tissue repair is still a challenge in reconstructive surgery peripheral nerves are capable of regenerating to some extent
Wettability of electrospun fibrous scaffolds was investigated by measuring their water contact angles (WCAs) at room temperature with a WCA measuring machine (SL200B, Shanghai Solon Tech Inc Ltd, China)
The ultimate tensile strength (UTS), elastic modulus (EM), and elongation at break (EB) of scaffold samples were determined according to the recorded stress–strain curves

Summary

Introduction

Peripheral nerve tissue repair is still a challenge in reconstructive surgery peripheral nerves are capable of regenerating to some extent. Synthetic nerve guidance conduits (NGCs) mimicking the composition and structure of an autograft have been investigated as a promising alternative treatment for peripheral nerve injury. These artificial scaffold-based conduits may support axonal growth and provide various biological cues [3,4,5,6]. Neurotrophic factors (NTFs) including nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) are known to promote neuronal survival, axonal regeneration, and Schwann cells migration [7]. Contact guidance provided by topographical cues by NGCs can promote neuronal growth and axonal extension [10, 11]. Scaffolds capable of achieving delivery of multiple NTFs with distinct release kinetics, spatial delivery of NTFs at different loci and topographical guidance are expected for much enhanced peripheral nerve regeneration

Objectives

Methods

Results

Discussion

Conclusion