AccScience Publishing / IJB / Online First / DOI: 10.36922/ijb.5717
RESEARCH ARTICLE
Early Access

A 3D bioprinted neuroinflammatory co-culture model for in vitro study of parkinson's disease pathology

Hongliang Mao1 Liangchen Yu1 Yang Qiao1 Menghui Liu1 Xingliang Dai1, 2* Hongwei Cheng1*
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1 Department of Neurosurgery, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, P. R. China
2 Department of Research & Development, East China Institute of Digital Medical Engineering, Shangrao, 334000, P. R. China
Submitted: 29 October 2024 | Accepted: 16 December 2024 | Published: 16 December 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

This study developed a 3D bioprinted neuroinflammatory co-culture model to simulate key pathological features of Parkinson’s disease (PD) in vitro. PD, a common neurodegenerative disorder, is characterized by dopaminergic (DA) neuron apoptosis, mitochondrial dysfunction, and aggregation of α-synuclein (α-syn). Traditional 2D cell culture models fail to accurately replicate the complex microenvironment of PD, leading to the development of this 3D bioprinted model. Utilizing a polyethylene glycol-hyaluronic acid methacryloyl (PEG-HAMA) hydrogel matrix, this model supports the co-culture of DA  neurons and microglia, allowing a more accurate representation of PD pathology. Experimental results demonstrated that, under 6-hydroxydopamine (6-OHDA) induction, the 3D model successfully mimicked neuroinflammatory responses associated with PD, including M1 polarization of microglia and increased secretion of pro-inflammatory factors. Compared to traditional 2D models, DA  neurons in the 3D model exhibited greater resistance to oxidative stress and neurotoxic challenges, with significantly slower rates of apoptosis. Additionally, the 3D model displayed key PD-specific pathological features, such as altered mitochondrial membrane potential, elevated reactive oxygen species (ROS) levels, and overexpression of α-syn. This 3D bioprinted PD model provides a closer-to-physiological platform for investigating the pathogenesis of PD and holds potential for use in drug screening. However, further optimization is required to enhance the model’s complexity and long-term stability, including incorporating peripheral immune cells to better simulate the progression of chronic neuroinflammation.

Keywords
3D bioprinting
Parkinson’s disease
Neuroinflammation
Dopaminergic neurons
α-synuclein aggregation
Funding
This article was partially supported by: the National Natural Science Foundation of China (82473256); the Anhui Province Higher Education Scientific Research Project, China (2024AH050818); the Research Fund of Anhui Institute of Translational Medicine (2023zhyx-C19); the Health Research Program of Anhui (AHWJ2023A30007); the Anhui Provincial Natural Science Foundation (2208085MH251); the Anhui Provincial Quality Engineering Project for Higher Education (2022jyxm761); the Fundamental Research Funds for the Anhui Medical University (2021xkj131); the Jiangxi Provincial Natural Science Foundation (20242BAB25521); Ganpo Promising Talents Supporting Plan: Talent Development Project of Leading Academic and Technological Researchers in Key Disciplines (20243BCE51060).
Conflict of interest
The authors declare they have no competing interests.
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing