Astrocytes (or astroglia) outnumber neurons 5-1 in the central nervous system, and are important in maintaining homeostasis within the CNS. In 2014, we showed that electrospun fiber scaffolds can increase glutamate uptake in astrocytes to protect neurons from excitotoxic death. We are currently optimizing the electrospun fiber scaffolds to promote astrocyte growth and to improve astrocyte neuroprotective potential after spinal cord injury. We also study how the nanotopography on implantable electrodes can help to reduce glial scarring on implanted alumina electrodes.
Dorsal Root Ganglia (DRG)
We utilize DRG in in vitro culture models to assess the neuroregenerative potential of our various biomaterial scaffolds. DRG isolate from chick embryos, rat, and mice, are also used within the Gilbert lab to assess bioactivity of drugs and proteins being released from our material scaffolds.
In SCI, macrophages infiltrate the lesion, phagocytosing debris, producing reactive oxygen species, and secreting cytokines. Using our biomaterials, we aim to dampen the pro-inflammatory macrophage response to enable white matter tract regeneration. We have incorporated anti-oxidants and anti-inflammatory cytokines into electrospun fibers and films and are studying the effect of these materials on peritoneal macrophage polarization in vitro. To determine whether these materials are pro-regenerative, we are co-culturing macrophages and dorsal root ganglion on these surfaces, studying neurite outgrowth.
Schwann Cells are the myelinating glial cells found in the peripheral nervous system, and play a key role in the response to peripheral nerve injury. Using biomaterials, we aim to promote a pro-regenerative Schwann Cell phenotype, in order to create a favorable microenvironment and facilitate nerve regeneration. Schwann Cells are being cultured on biomaterial scaffolds in the lab, and gene expression is analyzed to determine phenotypic changes.
Coated materials have the capability to provide a local, sustained release of drugs on the surfaces of implants and to lesion sites. Polymerized drug coatings are currently being used in the Gilbert lab with cortical microelectrodes to mitigate tissue damage at the implant site. We aim to dampen the pro-inflammatory macrophage and microglial response, reduce glial scarring, and prevent neuronal death around the electrode.
Electrospun fibers are frequently used as directional growth conduits for tissue regeneration applications. In the Gilbert lab, electrospun fibers are fabricated to promote regenerative phenotypes of astrocytes in cultures, and to facilitate directed neurite extension along the fibers. Alternatively, the Gilbert lab fabricates functionalized electrospun fiber scaffolds that can release a multitude of drugs or proteins to promote regeneration after SCI.
Hydrogels are polymer biomaterials that provide structural support and have the capability to deliver drugs to lesion sites. We use hydrogels for in vitro 3D spinal cord injury models. We study neuron and astrocyte extension and migration along electrospun fibers within hydrogels. Furthermore, we are using hydrogels to model drug release from biomaterials within a 3D space.
Nanoparticles & Microparticles
The Gilbert lab uses a variety of polymeric or magnetic nanoparticles for SCI applications. Polymeric nanoparticles are used frequently within the lab as drug or protein delivery vehicles. Magnetic nanoparticles are currently being used in the lab for their potential to allow electrospun fiber scaffolds to be magnetically aligned after implantation in animal models of SCI.