This Career award by the Biomaterials program in the Division of Materials Research to Rensselaer Polytechnic Institute is to develop novel biomaterials and cell culture techniques that modulate the reactivity of astrocytes. Astrocytes formed in the scar tissues after spinal cord injury create a barrier, and this barrier prevents the regeneration of axons and recovery from spinal cord injury. This proposal aims to develop biomaterials that attenuate astrocyte response following spinal cord injury and construct novel biomaterial approaches to support axonal migration through glial-scar interfaces. To attenuate astrocyte response, different peptides and proteins will be doped within aligned polymer fiber substrates. Astrocytes will be seeded onto the nanofiber substrates and the following parameters will be assessed: 1) dynamic and static astrocyte migration; 2) astrocyte activation/reactivity using molecular biology techniques; and 3) astrocyte stiffness using atomic force microscopy. Polymer spheres containing iron oxide nanoparticles with the chemo-attractants such as cyclic adenosine monophophate and brain derived neurotrophic factor will be developed to create magnetically moveable chemo-attractant gradients. These moveable gradients are expected to foster the directed extension of axonal growth cones through astrocytes or the inhibitory proteoglycan aggrecan. The proposal supports the education of undergraduate and graduate students in developing novel biomaterial scaffolds, isolation and culture of astrocytes and neurons. In addition, students will be trained in the assessment of cellular behavior using molecular biology and advanced microscopy techniques.
Individuals with spinal cord injury lose body functions below the site of injury leading to life-long paralysis. At present, no FDA approved biological, pharmacological, and/or biomaterial treatments exist to restore the lost functions. The goal of this proposal is to develop novel biomaterials to attenuate or eliminate the reactivity of astrocytes, a glial cell found in the scar tissues of the spinal cord that are known to produce factors inhibiting the nerve regeneration. Additionally, magnetically inducible polymer spheres will be developed to guide axons through inhibitory domains. It is believed that these biomaterials can reduce the inhibitory nature of astrocytes and help promote directed migration and regeneration of nerve axons. The experiments proposed within this proposal will provide the framework for developing novel strategies and treatments for spinal cord injury. In addition, the proposal supports the education of undergraduates and graduate students in the areas of spinal cord injury research and biomaterial fabrication. Further, the proposal supports initiatives to educate students from elementary, junior high school and high school, and the general public about spinal cord injury and the field of biomaterials.
