Curcumin-releasing mechanically adaptive intracortical implants improve the proximal neuronal density and blood-brain barrier stability.
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 4weeks 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. 12weeks 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.
Department of Biomedical Engineering, Case Western Reserve University, 2071 Martin Luther King Jr Drive, Wickenden Building, Cleveland, OH 44106, USA; Advanced Platform Technology Center, L. Stokes Cleveland VA Medical Center, 10701 East Boulevard Mail Stop 151 AW/APT, Cleveland, OH 44106-1702, USA.
Kelsey A
KA
Potter
Adolphe Merkle Institute, University of Fribourg, Rte de l'Ancienne Papeterie, CH-1723 Marly, Switzerland.
Mehdi
M
Jorfi
Department of Biomedical Engineering, Case Western Reserve University, 2071 Martin Luther King Jr Drive, Wickenden Building, Cleveland, OH 44106, USA; Advanced Platform Technology Center, L. Stokes Cleveland VA Medical Center, 10701 East Boulevard Mail Stop 151 AW/APT, Cleveland, OH 44106-1702, USA.
Kyle T
KT
Householder
Adolphe Merkle Institute, University of Fribourg, Rte de l'Ancienne Papeterie, CH-1723 Marly, Switzerland.
E Johan
EJ
Foster
Adolphe Merkle Institute, University of Fribourg, Rte de l'Ancienne Papeterie, CH-1723 Marly, Switzerland.
Christoph
C
Weder
Department of Biomedical Engineering, Case Western Reserve University, 2071 Martin Luther King Jr Drive, Wickenden Building, Cleveland, OH 44106, USA; Advanced Platform Technology Center, L. Stokes Cleveland VA Medical Center, 10701 East Boulevard Mail Stop 151 AW/APT, Cleveland, OH 44106-1702, USA. Electronic address: jeffrey.capadona@case.edu.
Jeffrey R
JR
Capadona
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D001713:Biphenyl Compounds / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002452:Cell Count; D002482:Cellulose / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology*; D002921:Cicatrix / Q000473:pathology; D003474:Curcumin / Q000737:chemistry / Q000494:pharmacology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D024243:HMGB1 Protein / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D020007:Implants, Experimental; D007249:Inflammation / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D053758:Nanoparticles; D009439:Neuraminidase / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D010539:Permeability / Q000187:drug effects; D010851:Picrates / Q000378:metabolism; D011142:Polyvinyl Alcohol / Q000737:chemistry; D051381:Rats; D014561:Urochordata / Q000737:chemistry; D014945:Wound Healing / Q000187:drug effects
D000975:Antioxidants; D001713:Biphenyl Compounds; D005904:Glial Fibrillary Acidic Protein; D024243:HMGB1 Protein; D007074:Immunoglobulin G; D010851:Picrates; D011142:Polyvinyl Alcohol; D002482:Cellulose; C004931:1,1-diphenyl-2-picrylhydrazyl; D009439:Neuraminidase; D003474:Curcumin
Blood–brain barrier; Curcumin; Intracortical microelectrodes; Mechanically adaptive; Neuroinflammation