Engineering a Core-Shell Electrospun Nerve Wrap For The Controlled Release Of FK506
Katelyn Chan, B.Eng BioSci1,2; Marina Manoraj,1,2; Kasra Tajdaran, MASc, PhD1,2; Tessa Gordon, PhD2,3; Gregory H. Borschel, MD, FAAP, FACS1,2,3
1Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada, 2Division of Plastic and Reconstructive Surgery, The Hospital for Sick Children, Toronto, ON, Canada, 3Division of Plastic and Reconstructive Surgery, University of Toronto, Toronto, ON, Canada
Introduction: Locally delivered FK506, an FDA-approved drug, encapsulated in biodegradable poly(lactic-co-glycolic) acid (PLGA) microspheres and fibrin gel, enhances peripheral nerve regeneration in rats. Though effective, this process may be made more clinically feasible by reducing the number of components and manufacturing steps. Electrospinning is a one-step process to create polymer fibrous mats with tunable properties. Co-axial electrospinning allows a drug to be encapsulated as a core fiber within an outer layer to sustain drug release and minimize burst release. Our aim is to control FK506 release for effective enhancement of nerve regeneration by incorporating FK506 in core-shell electrospun polymer fibers that can be shaped and applied as a nerve wrap to localize FK506 at the nerve repair site.
Materials/Methods: A co-axial nozzle of two concentric 22 and 18 gauge blunt-tip needles for inner and outer shells, respectively, was used to form core-shell fibers with an outer shell of 20 w/v% PLGA [85 lactic acid (LA): 15 glycolic acid (GA) groups] and an inner shell of 20 w/v% PLGA (85 LA :15 GA) and 1 w/v% FK506. The fibers were compared to uniaxial electrospun fibers of the same composition, spun with an 18-gauge needle, but with or without FK506. A constant flow rate of 1 mL/h was used with a voltage difference of 1 kV/cm. Separate mats were used for all experiments (n=3). Scanning electron microscopy and ImageJ and DiameterJ software were used to determine fiber diameter and porosity.
Results: Electrospun core-shell fibers with FK506 were smooth with no beading, indicating their successful formation as beaded fibers are undesirable because of likely mechanical instability. The mean ± SE of core-shell fiber diameter and the porosity were 770 ± 34 nm and 40 ± 2%, respectively. The mean fiber diameters and porosity for the uniaxial fibers with or without FK506 were 793 ± 26 nm and 42 ± 1.4% or 678 ± 26 nm and 41 ± 1.5%, respectively. There were no significant differences between groups.
Conclusions: No significant differences in mean fiber diameter and porosity between all groups indicate that FK506 inclusion does not affect fiber morphology. The relatively large fiber diameter and low porosity of the core-shell electrospun fibers may result in better drug loading and an extended drug release period, along with protection from burst release of drug. The smooth viable electrospun fibers have the potential to form nerve wraps to enhance peripheral nerve regeneration with FK506 release.
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