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A three-dimensional biomimetic peripheral nerve model for drug testing and disease modelling
Afonso Malheiro1, Francis Morgan1, Matthew Baker1
1Department of Complex Tissue Regeneration, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, 6200 MD, Maastricht, the Netherlands.
Biomaterials
|August 1, 2020
Summary
We developed a novel 3D biomimetic peripheral nerve model using Schwann cells and PC12 cells for cost-effective drug screening. This platform accurately mimics nerve development and pathology, reducing the need for animal testing.
Area of Science:
- Biomaterials Science
- Neuroscience
- Drug Discovery
Background:
- In vitro peripheral nerve models are crucial for studying neurobiology and drug efficacy in regenerative medicine and disease contexts.
- Existing models often lack the complexity of native nerve tissue, limiting their predictive power for drug screening.
Purpose of the Study:
- To develop a simple, low-cost, and representative in vitro model of peripheral nerve tissue.
- To create a 3D platform that exhibits neural anisotropy and myelination for drug screening applications.
Main Methods:
- Constructed a 3D model using rat primary Schwann cells (SCs) on electrospun scaffolds (forming Bands of Büngner), primed PC12 cells as neurons, and fibrin hydrogel.
- Validated PC12 cells against rat dorsal root ganglion (DRG) neurons, observing aligned neurites and myelination in both.
- Assessed neurite outgrowth and myelination under various conditions, including short-term (7 days) and mature (28 days) cultures, and tested drug effects and pathological mimicry (hyperglycemia).
Main Results:
- The 3D model successfully demonstrated neural anisotropy and myelination, with SCs and fibrin hydrogel enhancing neurite outgrowth.
- The model accurately mimicked immature and mature nerve development, allowing for the observation of drug effects (e.g., suramin neurotoxicity, epalrestat's effect on myelin) and pathological conditions (hyperglycemic-induced myelin deformation).
- The platform using PC12 cells yielded results comparable to primary DRG neurons, avoiding the need for repeated animal sacrifice.
Conclusions:
- A biomimetic 3D peripheral nerve model was successfully developed using accessible cell lines and materials.
- This platform offers a cost-effective and convenient method for drug screening in both normal and pathological peripheral nerve states.
- The model holds significant promise for advancing peripheral nerve research and pharmaceutical development.
