Abstract
The surface of aligned, electrospun poly-L-lactic acid (PLLA) fibers was chemically modified to determine if surface chemistry and hydrophilicity could improve neurite extension from chick dorsal root ganglia. Specifically, diethylenetriamine (DTA, for amine functionalization), 2-(2-aminoethoxy)ethanol (AEO, for alcohol functionalization), or GRGDS (cell adhesion peptide) were covalently attached to the surface of electrospun fibers. Water contact angle measurements revealed that surface modification of electrospun fibers significantly improved fiber hydrophilicity compared to unmodified fibers (p < 0.05). Scanning electron microscopy (SEM) of fibers revealed that surface modification changed fiber topography modestly, with DTA modified fibers displaying the roughest surface structure. Degradation of chemically modified fibers revealed no change in fiber diameter in any group over a period of seven days. Unexpectedly, neurites from chick DRG were longest on fibers without surface modification (1651 ± 488 μm) and fibers containing GRGDS (1560 ± 107 μm). Fibers modified with oxygen plasma (1240 ± 143 μm) or DTA (1118 ± 82 μm) produced shorter neurites than the GRGDS or unmodified fibers, but were not statistically shorter than unmodified and GRGDS modified fibers. Fibers modified with AEO (844 ± 151 μm) were significantly shorter than unmodified and GRGDS modified fibers (p<0.05). Based on these results, we conclude that fiber hydrophilic enhancement alone on electrospun PLLA fibers does not enhance neurite outgrowth. Further work must be conducted to better understand why neurite extension was not improved on more hydrophilic fibers, but the results presented here do not recommend hydrophilic surface modification for the purpose of improving neurite extension unless a bioactive ligand is used.
Highlights
Autologous peripheral nerve grafts have been used to restore function after spinal cord injury (SCI) in animal models to recover limb function,[1] respiratory function,[2] and most recently bladder control.[3]
The longevity of the surface modification may be an important consideration for some applications, such as spinal cord injury where months of axonal extension are required in order to achieve recovery of lost function in rodents.[2,3]
We determined the presence of functional groups on the surface of electrospun, poly-L-lactic acid (PLLA) fibers at short time points after degradation in PBS to understand how long the functional groups remained on the surface
Summary
Autologous peripheral nerve grafts have been used to restore function after spinal cord injury (SCI) in animal models to recover limb function,[1] respiratory function,[2] and most recently bladder control.[3]. Many synthetic guidance approaches are studied in animal models of SCI.[5,6] One alternative approach to the autologous nerve graft is electrospinning, which is capable of creating aligned fibers with diameters on the nano to micro scale (reviewed by Lee and Livingston Arinzeh).[7] Electrospun fibers have the potential to direct axonal regeneration when fibers are highly aligned.[8,9,10,11,12] therapeutic agents can be encapsulated in the polymer [13] for local, sustained delivery without compromising the fiber’s ability to guide axons.[14,15] Several recent studies have used electrospun fibers in animal models of SCI The results from these studies reveal the ability of electrospun containing scaffolds to direct axonal regeneration [16,17] and astrocyte migration.[18] Some studies have observed recovery of lost function when animals received electrospun fiber treatment in specific injury models more conducive to functional recovery (hemisection model vs complete transection model).[19] Some studies have observed recovery of lost function when animals received electrospun fiber treatment in specific injury models more conducive to functional recovery (hemisection model vs. complete transection model).[19]
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