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Molecular Mechanisms of Foreign Body Responses to Neural Electrodes and Surface Biofunctionalization Strategies for
Ziliang He1,2,3, Junlong Ma3,4,5, Yun Liu4,5
1Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen 518055, China.
International Journal of Molecular Sciences
|August 13, 2026
Summary
The foreign body response (FBR) to neural electrodes limits device longevity by causing tissue damage and scar formation. Biofunctionalization strategies are crucial for designing durable neural electrodes by addressing these molecular mechanisms.
Area of Science:
- Biomedical Engineering
- Neuroscience
- Materials Science
Background:
- Long-term neural electrodes are vital for brain-machine interfaces and neuromodulation therapies.
- The foreign body response (FBR) at the electrode-tissue interface significantly degrades neural electrode performance over time.
- This FBR involves complex molecular events including inflammation, glial scarring, and neuronal loss.
Purpose of the Study:
- To review the molecular mechanisms underlying the neural-electrode foreign body response.
- To connect these mechanisms with various surface biofunctionalization strategies.
- To guide the rational design of durable neural electrodes.
Main Methods:
- Literature review of molecular mechanisms of neural-electrode FBR.
- Analysis of surface biofunctionalization strategies.
- Establishing links between molecular events, material interfaces, and functionalization.
Main Results:
- The FBR involves implantation injury, protein adsorption, blood-brain barrier disruption, complement activation, glial reactivity, oxidative stress, glial scar formation, and neuronal loss.
- These events lead to increased impedance, reduced signal quality, and higher stimulation thresholds.
- Current biofunctionalization strategies include antifouling coatings, bioactive ligands, neurotrophic factors, drug-eluting electrodes, and immunomodulatory interfaces.
Conclusions:
- The foreign body response is a multifactorial process, not solely due to material aging or encapsulation.
- Understanding the molecular mechanisms is key to developing effective biofunctionalization strategies.
- Rational design of durable neural electrodes requires mechanistic insights into FBR and biofunctionalization.
