Dual Delivery and Sustained Release of Growth Factors from Electrospun Bicomponent Scaffolds for Nerve Tissue Engineering

Abstract

Repairing peripheral nerve damages caused by nerve trauma, compression or tumor is still a challenge. For severe nerve defects, appropriate devices for bridging and guiding axons are necessary. Neural autograft segments can be used for such purposes but limited availability of donor nerves and function loss of donor sites have hampered the use of autografts. Tissue engineering nerve guides are a promising alternative. A variety of techniques can produce 3D scaffolds with various architectures and properties but electrospinning and electrospun fibrous scaffolds have attracted great attention owing to many advantages. In nerve tissue repair, nanofibrous scaffolds can provide favourable conditions for Schwann cell migration and for guiding neurite outgrowth. Delivering locally growth factors such as nerve growth factor (NGF) and glial cell line-derived growth factor (GDNF) can promote a range of neural responses and affect cell fate. In this investigation, for dual delivery and sustained release of growth factors, bicomponent nanofibrous scaffolds containing NGF and GDNF were fabricated via dual-source dual-power electrospinning and then evaluated. NGF and GDNF were encapsulated in PDLLA fibers and PLGA fibers, respectively, through emulsion electrospinning. The mass ratio of NGF/PDLLA fibers to GDNF/PLGA fibers in bicomponent scaffolds could be varied to modulate growth factor release. Through optimization, uniform fibers were made and both types of fibers were evenly distributed in bicomponent scaffolds. Using various techniques, the structure and properties of bicomponent scaffolds were studied. Core-shell structures were formed for both types of fibers, with the growth factor-containing water phase being the core. All fibrous scaffolds exhibited good wettability. In vitro degradation of scaffolds and in vitro release of both growth factors were investigated for up to 42 days. The degradation rate of NGF/PDLLA fibers was much lower than that of GDNF/PLGA fibers due to slower degradation of PDLLA. The degradation rate of bicomponent scaffolds increased with an increasing amount of GDNF/PLGA fibers. Scaffolds with fibers of different diameters exhibited different degradation rates. NGF and GDNF were both successfully incorporated in bicomponent scaffolds with relatively high encapsulation efficiency. Sustained release of both growth factors was observed. The release of GDNF from mono- or bicomponent scaffolds was much faster than that of NGF. The cumulative release amount of NGF or GDNF increased with an increasing amount of NGF/PDLLA fibers or GDNF/PLGA fibers in bicomponent scaffolds, and increased with a decrease in fiber diameter. The cellular response, including cytocompatibility, cell migration and neurite outgrowth, to the scaffolds was also assessed.