Journal
ACTA BIOMATERIALIA
Volume 10, Issue 5, Pages 2209-2222Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2014.01.018
Keywords
Curcumin; Intracortical microelectrodes; Mechanically adaptive; Blood-brain barrier; Neuroinflammation
Funding
- Department of Biomedical Engineering Case Western Reserve University through laboratory start-up funds (J.R.C.)
- Medtronic Graduate Fellowship
- Rehabilitation Research and Development of Veterans Affairs Merit Review [J.R.C., B71 22R]
- Swiss National Science Foundation [NRP 62: Smart Materials, 406240_126046]
- Adolphe Merkle Foundation (C.W.)
- Swiss National Science Foundation (SNF) [406240_126046] Funding Source: Swiss National Science Foundation (SNF)
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The cellular and molecular mechanisms by which neuroinflammatory pathways respond to and propagate the reactive tissue response to intracortical microelectrodes remain active areas of research. We previously demonstrated that both the mechanical mismatch between rigid implants and the much softer brain tissue, as well as oxidative stress, contribute to the neurodegenerative reactive tissue response to intracortical implants. In this study, we utilize physiologically responsive, mechanically adaptive polymer implants based on poly(vinyl alcohol) (PVA), with the capability to also locally administer the antioxidant curcumin. The goal of this study is to investigate if the combination of two independently effective mechanisms - softening of the implant and antioxidant release - leads to synergistic effects in vivo. Over the first 4 weeks of the implantation, curcumin-releasing, mechanically adaptive implants were associated with higher neuron survival and a more stable blood-brain barrier at the implant-tissue interface than the neat PVA controls. 12 weeks post-implantation, the benefits of the curcumin release were lost, and both sets of compliant materials (with and without curcumin) had no statistically significant differences in neuronal density distribution profiles. Overall, however, the curcumin-releasing softening polymer implants cause minimal implant-mediated neuroinflammation, and embody the new concept of localized drug delivery from mechanically adaptive intracortical implants. Published by Elsevier Ltd. on behalf of Acta Materialia Inc.
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