Reducing Astrocytic Scarring after Traumatic Brain Injury with a Multifaceted Anti-Inflammatory Hydrogel System

Traumatic brain injury results in devastating long-term functional damage due to the growth inhibition of the inflammatory response, and in particular, the complex response of astrocytes. Sustained, nonsteroidal anti-inflammatory approaches that can attenuate this response are of interest to improve therapeutic outcomes, particularly when combined with a tissue engineering construct that recapitulates the physiological microenvironment to facilitate functional repair. Here, we present a multifaceted, therapeutic extracellular-matrix mimic consisting of a coassembled scaffold with a laminin-inspired self-assembling peptide hydrogel, Fmoc-DIKVAV, and the anti-inflammatory macromolecule, fucoidan. At 7 days post-injury, our novel multicomponent hydrogel system presenting biologically relevant nanofibers and the anti-inflammatory fucoidan attenuated the primary glial scar to half that of a stab (control) injury. Further, the presentation of fucoidan increased the organization of astrocytes within the glial scar, while also significantly changing the morphology of astrocytes distal from the administered hydrogel and further into the parenchyma. This demonstrates that the anti-inflammatory fucoidan, present on the surface of the Fmoc-DIKVAV nanofibers, causes a change in astrocyte phenotype post-injury attenuating "reactive" astrocytosis. For the first time, we present a multicomponent tissue engineering construct to promote a growth-permissive environment in vivo and, thus, increase the potential for repair and regeneration after traumatic brain injury.