Sustained delivery of dbcAMP by poly(propylene carbonate) micron fibers promotes axonal regenerative sprouting and functional recovery after spinal cord hemisection

Abstract

This study describes the use of poly(propylene carbonate) (PPC) electrospun fibers as vehicle for the sustained delivery of dibutyryl cyclic adenosine monophosphate (dbcAMP) to the hemisected spinal cord. The dbcAMP and PPC were uniformly mixed with acetonitrile; then, electrospinning was used to generate micron fibers. The release of dbcAMP was assessed by ELISA in vitro. Our results showed that the encapsulation of dbcAMP in the fibers led to stable and prolonged release in vitro. The PPC micron fibers containing dbcAMP and the PPC micron fibers without dbcAMP were then implanted into the hemisected thoracic spinal cord, followed by testing of the functional recovery and immunohistochemistry. Compared with the control group, sustained delivery of dbcAMP promoted axonal regenerative sprouting and functional recovery and reduced glial scar formation, and the PPC micron fibers without dbcAMP did not have these effects. Our findings demonstrated the feasibility of using PPC electrospun fibers containing dbcAMP for spinal cord injury. The approach described here also will provide a platform for the potential delivery of other axon-growth-promoting or scar-inhibiting agents.

Keywords: 3,3′-diaminobenzidine; BBB; Basso, Beattie, and Bresnahan; CO(2); DAB; DMEM; Dulbecco's modified Eagle's medium; ELISA; Electrospinning; GAP-43; GFAP; NF-200; PPC; SCI; SEM; Spinal cord injury; carbon dioxide; chABC; chondroitin sulfate ABC; dbcAMP; dibutyryl cyclic adenosine monophosphate; enzyme-linked immunosorbent assay; glial fibrillary acidic protein; growth-associated protein 43; neurofilament-200; poly(propylene carbonate); scanning electron microscopy; spinal cord injury.