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

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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.