A 3D Tissue Model of Traumatic Brain Injury with Excitotoxicity That Is Inhibited by Chronic Exposure to Gabapentinoids

Injury progression associated with cerebral laceration is insidious. Following the initial trauma, brain tissues become hyperexcitable, begetting further damage that compounds the initial impact over time. Clinicians have adopted several strategies to mitigate the effects of secondary brain injury; however, higher throughput screening tools with modular flexibility are needed to expedite mechanistic studies and drug discovery that will contribute to the enhanced protection, repair, and even the regeneration of neural tissues. Here we present a novel bioengineered cortical brain model of traumatic brain injury (TBI) that displays characteristics of primary and secondary injury, including an outwardly radiating cell death phenotype and increased glutamate release with excitotoxic features. DNA content and tissue function were normalized by high-concentration, chronic administrations of gabapentinoids. Additional experiments suggested that the treatment effects were likely neuroprotective rather than regenerative, as evidenced by the drug-mediated decreases in cell excitability and an absence of drug-induced proliferation. We conclude that the present model of traumatic brain injury demonstrates validity and can serve as a customizable experimental platform to assess the individual contribution of cell types on TBI progression, as well as to screen anti-excitotoxic and pro-regenerative compounds

Evaluation of the Osteoinductive Capacity of Polydopamine-Coated Poly(ε-caprolactone) Diacrylate Shape Memory Foams

Recently, a novel shape memory polymer foam based on the photopolymerization of poly­(ε-caprolactone) diacrylate (PCLDA) has been developed. These PCLDA foams enter a temporary softened state when briefly treated with warm saline (<i>T</i>_saline > <i>T</i>_m of PCLDA), allowing them to conform to irregular bone defect “boundaries” prior to shape setting. When coated with a mechanically stable polydopamine (PD) layer, these PCLDA foams have previously been demonstrated to induce hydroxyapatite deposition. In the present study, the osteoinductivity of these “self-fitting” PD-coated PCLDA (PD–PCLDA) materials was evaluated relative to uncoated PCLDA (U-PCLDA) controls using bone marrow-derived human mesenchymal stem cells (h-MSCs). When cultured in the absence of osteogenic media supplements, PD–PCLDA scaffolds expressed similar levels of Runx2, alkaline phosphatase, and osteopontin protein as U-PCLDA scaffolds cultured in the presence of osteogenic media supplements. In addition, PD–PCLDA scaffolds cultured without osteogenic supplements did not significantly promote undesired lineage progression (e.g., adipogenesis or chondrogenesis) of h-MSCs. Cumulatively, these data indicate that PD–PCLDA materials display increased osteoinductivity relative to U-PCLDA substrates. Future studies will examine tethered osteogenic factors or peptides toward augmenting the osteoinductive properties of the PD–PCLDA foams