Engineering a core-shell electrospun fiber nerve wrap for the localized release of FK506

Katelyn Chan (1,2), Marina Manoraj (1), Jenny Cheung (2), Tessa Gordon(2), Gregory Borschel (1,2)

(1) Institute of Biomaterials and Biomedical Engineering, University of Toronto

(2) Division of Plastic and Reconstructive Surgery, The Hospital for Sick Children

FK506, an FDA-approved drug, encapsulated in biodegradable microspheres and hydrogel, enhances peripheral nerve regeneration in rats. Though effective, this process is not user-friendly enough for human surgical use. We hypothesize that incorporating FK506 in a nerve wrap will be a simpler and more clinically-feasible method to locally deliver FK506 and improve regeneration following microsurgical repair. We aim to develop an implantable FK506 delivery nerve wrap with suitable properties for clinical application, to sustain bioactive release of FK506, and be biocompatible and biodegradable. Electrospinning is a one-step process to create polymer fibrous mats. Co-axial electrospinning allows a drug to be encapsulated as a core fiber within an outer layer to sustain and optimize drug release. A co-axial nozzle was used to electrospin core-shell fibers with an outer shell of 20 w/v% polycarbonate urethane (PCNU), an inner shell of 14 w/v% PCNU and 1 w/v% FK506. The resulting fibrous mats were then vacuum dried and sectioned into nerve wraps. Fiber diameter and porosity were determined using scanning electron microscopy. Tensile tests were conducted to measure the dry elastic modulus. Thermogravimetric analysis was conducted to understand the degradation and thermal stability of the nerve wraps. Mass spectrometry was used to determine the encapsulation efficiency of FK506 within the core-shell fibers. The means ± standard deviation of the fiber diameter and porosity were 320 ± 70 nm and 40 ± 10%, respectively, and of the dry elastic modulus, 2.38 ± 1.05 MPa. The physical properties of the nerve wrap indicate a longer degradation rate to prolong FK506 delivery and high tensile strength to withstand surgical forces. The core-shell PCNU and FK506 fibrous nerve wraps were thermally stable up to around 260°C and thus, could resist temperature-induced degradation under physiological conditions (37°C). The FK506 encapsulation efficiency was 92 ± 14%, indicating complete availability of FK506 to encourage peripheral nerve regeneration following implantation of the nerve wrap. Therefore, the electrospun PCNU and FK506 fibers have the potential to form clinically useful and feasible nerve wraps that enhance peripheral nerve regeneration due to their simplicity and ideal physical properties. Future work is being conducted to extend the FK506 release profile and quantify biocompatibility and bioactivity of FK506 following encapsulation.

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