NEUral Regeneration with conducTivE Scaffolds

Project PTDC/CTM-COM/32606/2017

Regrowth of severed axons, observed in the peripheral nervous system, is controlled by cellular and molecular responses. Macrophages are among the cells supporting axonal regeneration. The lack of cues to guide axonal growth cones from the proximal to the distal segments of the lesion, delays re-connection. Meanwhile, Wallerian degeneration at the distal segment ends up impairing functional recovery of large gaps. With the current grafting solutions, regeneration is limited to gaps below a critical size (~ 5 cm in humans). In the Central Nervous System, the problem gets worse due to the local immune response that amplifies damage and leads to a cystic cavity surrounded by a scar that prevents axonal regrowth. Nevertheless, the potential for axonal regrowth still exists.

Multiple strategies to promote neuronal regeneration have been studied. Some conclusions are: nerve conduit scaffolds promote neural regeneration; guidance cues can be included in the scaffold by aligned electrospun fibres; scaffolds support cell transplantation; electrical stimulation applied through the scaffold guides neurite growth and influences proliferation and differentiation of various cell types.

In this project, we will optimize electrospun scaffolds of aligned fibres to be used in electrical stimulation (ES) of cells envisioning the promotion of neural regeneration. Electrical conductivity will be imparted to the scaffold, based on a biocompatible and biodegradable polymers (BP), by a conducting polymer (CP).

To achieve a scaffold with satisfactory conductivity, a CP percolating network should be interspersed in the BP. We will use some new strategies to polymerize the CP in order to achieve such a structure. The parameters of these strategies will be optimized. The electrospinning solutions will also be optimized to enhance solution and fiber uniformity.

ES will be applied to various human cells types. Some of these studies have never been done. We will correlate ES parameters with cell morphology, proliferation and differentiation. The results will elucidate on possible strategies to promote neuronal regeneration through ES.