Dopaminergic Axon Tracts Within a Hyaluronic Acid Hydrogel Encasement to Restore the Nigrostriatal Pathway.

Autor: Gordián-Vélez WJ; Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael Crescenz Veterans Affairs Medical Center, Philadelphia, PA, 19104, USA., Browne KD; Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael Crescenz Veterans Affairs Medical Center, Philadelphia, PA, 19104, USA., Galarraga JH; Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, 19104, USA., Chouhan D; Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael Crescenz Veterans Affairs Medical Center, Philadelphia, PA, 19104, USA., Duda JE; Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael Crescenz Veterans Affairs Medical Center, Philadelphia, PA, 19104, USA.; Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA., España RA; Department of Neurobiology & Anatomy, College of Medicine, Drexel University, Philadelphia, PA, 19104, USA., Chen HI; Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael Crescenz Veterans Affairs Medical Center, Philadelphia, PA, 19104, USA., Burdick JA; Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, 19104, USA.; BioFrontiers Institute and Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, CO, 80303, USA., Cullen DK; Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael Crescenz Veterans Affairs Medical Center, Philadelphia, PA, 19104, USA.
Jazyk: angličtina
Zdroj: Advanced healthcare materials [Adv Healthc Mater] 2024 Nov 04, pp. e2402997. Date of Electronic Publication: 2024 Nov 04.
DOI: 10.1002/adhm.202402997
Abstrakt: Parkinson's disease is characterized by motor deficits emerging from insufficient dopamine in the striatum after degeneration of dopaminergic neurons and their long-projecting axons comprising the nigrostriatal pathway. To address this, a tissue-engineered nigrostriatal pathway (TE-NSP) featuring a tubular hydrogel with a collagen/laminin core that encases aggregated dopaminergic neurons and their axonal tracts is developed. This engineered microtissue can be implanted to replace neurons and axons with fidelity to the lost pathway and thus may provide dopamine according to feedback from host circuitry. While TE-NSPs have traditionally been fabricated with agarose, here a hyaluronic acid (HA) hydrogel is utilized to have a more bioactive encasement while expanding control over physical and biochemical properties. Using rat ventral midbrain neurons, it is found that TE-NSPs exhibited improved neurite growth with HA relative to agarose, with no differences in electrically-evoked dopamine release. When transplanted, HA hydrogels reduced average host neuron loss and inflammation around the implant compared to agarose, and TE-NSP neurons and axonal tracts survived for at least 2 weeks to structurally emulate the lost pathway. This study represents an innovative use of HA hydrogels for neuroregenerative medicine and enables future studies expanding the control and functionality of TE-NSPs.
(© 2024 Wiley‐VCH GmbH.)
Databáze: MEDLINE
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