Journal article
Dopaminergic Axon Tracts Within a Hyaluronic Acid Hydrogel Encasement to Restore the Nigrostriatal Pathway
Advanced healthcare materials, v 14(2), 2402997
04 Nov 2024
Abstract
Abstract 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.
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Details
- Title
- Dopaminergic Axon Tracts Within a Hyaluronic Acid Hydrogel Encasement to Restore the Nigrostriatal Pathway
- Creators
- Wisberty J. Gordián-Vélez - University of PennsylvaniaKevin D. Browne - University of PennsylvaniaJonathan H. Galarraga - University of PennsylvaniaDimple Chouhan - University of PennsylvaniaJohn E. Duda - University of PennsylvaniaRodrigo A. España - Drexel UniversityH. Isaac Chen - University of PennsylvaniaJason A. Burdick - University of PennsylvaniaD. Kacy Cullen - University of Pennsylvania
- Publication Details
- Advanced healthcare materials, v 14(2), 2402997
- Publisher
- Wiley
- Number of pages
- 15
- Grant note
- Department of Veterans Affairs: I01-BX003748, IK2-RX002013 National Institutes of Health: R01-NS117757, R01-NS127895 National Science Foundation: DGE-1845298 Michael J. Fox Foundation: 9998.01
Financial support was provided by the Department of Veterans Affairs [Merit Review I01-BX003748 (Cullen) & Career Development Award #IK2-RX002013 (Chen)], the National Institutes of Health [R01-NS117757 (D.K.C.), R01-NS127895 (D.K.C.)], the National Science Foundation [Graduate Research Fellowship DGE-1845298 (Gordian-Velez, Galarraga)], and the Michael J. Fox Foundation [Therapeutic Pipeline Program 9998.01 (Cullen)]. Any opinion, findings, and conclusions or recommendations expressed in this material are those of the authors(s) and do not necessarily reflect the views of the Department of Veterans Affairs, National Institutes of Health, National Science Foundation, or the Michael J. Fox Foundation. The authors would like to acknowledge Matthew Fainor for helping with dynamic mechanical analysis.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:001358408700001
- Scopus ID
- 2-s2.0-85208031665
- Other Identifier
- 991021955215704721
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Engineering, Biomedical
- Materials Science, Biomaterials
- Nanoscience & Nanotechnology