Abstract
Electrospun fibrous scaffolds capable of providing dual growth factor delivery in a controlled manner have distinctive advantages for tissue engineering. In this study, we have investigated the formation, structure, and characteristics/properties of fibrous bicomponent scaffolds for the dual delivery of glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor (NGF) for peripheral nerve tissue regeneration. GDNF and NGF were incorporated into core-shell structured poly(lactic-co-glycolic acid) (PLGA) and poly (d,l-lactic acid) (PDLLA) nanofibers, respectively, through emulsion electrospinning. Using dual-source dual-power electrospinning, bicomponent scaffolds composed of GDNF/PLGA fibers and NGF/PDLLA fibers with different fiber component ratios were produced. The structure, properties, and in vitro release behavior of mono- and bicomponent scaffolds were systematically investigated. Concurrent and sustained release of GDNF and NGF from bicomponent scaffolds was achieved and their release profiles could be tuned. In vitro biological investigations were conducted. Rat pheochromocytoma cells were found to attach, spread, and proliferate on all scaffolds. The release of growth factors from scaffolds could induce much improved neurite outgrowth and neural differentiation. GDNF and NGF released from GDNF/PLGA scaffolds and NGF/PDLLA scaffolds, respectively, could induce dose-dependent neural differentiation separately. GDNF and NGF released from bicomponent scaffolds exerted a synergistic effect on promoting neural differentiation.
Highlights
Functional recovery of injured peripheral nerves still needs to be improved in clinic, especially for critical-size peripheral nerve injury
The results indicated that cumulative release amount of glial cell line-derived neurotrophic factor (GDNF) from scaffolds increased with the increase of GDNF/poly(lactic-co-glycolic acid) (PLGA) fiber to nerve growth factor (NGF)/PDLLA fiber ratio but with the decrease of fiber diameter
Fibrous bicomponent scaffolds for the dual delivery of growth factors were successfully produced through emulsion electrospinning and dual-source dual-power electrospinning (DSDP-ES)
Summary
Functional recovery of injured peripheral nerves still needs to be improved in clinic, especially for critical-size peripheral nerve injury. Local delivery of neurotrophic factors including nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) at surgical sites have been proposed to enhance peripheral nerve regeneration. These neurotrophic factors play important roles in neuronal survival, neural differentiation, and axonal regeneration independently or synergistically at different effective concentrations [1,2,3,4,5]. Few studies have been conducted to investigate the influence of dual and sustained neurotrophic factor delivery at biologically effective neurotrophic factor concentrations on neurite outgrowth that may be important for enhanced nerve repair and functional recovery. Suitable delivery vehicles are needed for controlled and sustained delivery of these therapeutic biomolecules due to their vulnerability and short half-life through direct administration [7, 8]
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