Abstract
The central nervous system shows limited regenerative capacity after injury. Spinal cord injury (SCI) is a devastating traumatic injury resulting in loss of sensory, motor, and autonomic function distal from the level of injury. An appropriate combination of biomaterials and bioactive substances is currently thought to be a promising approach to treat this condition. Systemic administration of valproic acid (VPA) has been previously shown to promote functional recovery in animal models of SCI. In this study, VPA was encapsulated in poly(lactic-co-glycolic acid) (PLGA) microfibers by the coaxial electrospinning technique. Fibers showed continuous and cylindrical morphology, randomly oriented fibers, and compatible morphological and mechanical characteristics for application in SCI. Drug-release analysis indicated a rapid release of VPA during the first day of the in vitro test. The coaxial fibers containing VPA supported adhesion, viability, and proliferation of PC12 cells. In addition, the VPA/PLGA microfibers induced the reduction of PC12 cell viability, as has already been described in the literature. The biomaterials were implanted in rats after SCI. The groups that received the implants did not show increased functional recovery or tissue regeneration compared to the control. These results indicated the cytocompatibility of the VPA/PLGA core-shell microfibers and that it may be a promising approach to treat SCI when combined with other strategies.
Highlights
Electrospun nanofibers are regarded as a very promising extracellular matrix-mimicking system and an effective delivery system of biomolecules, which can provide physical support for cellular growth to modulate tissue regeneration [1,2].Spinal cord injury (SCI) is a major cause of paralysis
Poly(lactic-co-glycolic acid) (PLGA) has been used in many tissue engineering applications due to its biodegradability and biocompatibility [16]. This is the first study to demonstrate the potential of encapsulating valproic acid (VPA) in electrospun microfibers and its application in SCI repair
To provide evidence of the successful incorporation of VPA into fibers, fluorescein was loaded as the core solution and its distribution inside the nanofiber was observed by confocal microscopy
Summary
Spinal cord injury (SCI) is a major cause of paralysis This lesion damages axonal pathways, interrupting synaptic transmission between the brain and spinal cord and subsequently altering motor, sensory, and autonomic functions below the level of injury [3]. There is no effective clinical treatment to date for this condition and current treatment focuses on stabilization and prevention of further damage. For this reason, many studies propose the use of biomaterials to repair the broken neuronal circuitry of the injured spinal cord. Implantable biomaterials can be mainly used to regenerate a damaged area of the spinal cord, bridge the formed gap, and act as support for axonal re-growth [5]
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