DNase I functional microgels for neutrophil extracellular trap disruption
Aisa Hosseinnejad1, Nadine Ludwig2, Ann-Katrin Wienkamp2
1DWI-Leibniz-Institute for Interactive Materials e.V., Forckenbeckstr. 50, 52056 Aachen, Germany.
Biomaterials Science
|November 23, 2021
Summary
Neutrophil extracellular traps (NETs) cause thrombosis on artificial surfaces. Conjugating DNase I to microgels improved its stability and NET-degrading ability, offering a novel anti-thrombotic coating.
Area of Science:
- Biomaterials Science
- Immunology
- Hematology
Background:
- Neutrophil extracellular traps (NETs) are implicated in thrombosis, particularly on artificial surfaces like medical devices.
- The enzyme DNase I degrades NETs but has limited therapeutic use due to poor serum stability.
Purpose of the Study:
- To develop a stable and effective DNase I formulation for treating NET-mediated thrombosis.
- To create a biohybrid platform using DNase I conjugated to non-fouling microgels.
Main Methods:
- DNase I was conjugated to microgels synthesized from HPMA and CBMAA.
- Enzymatic activity (Km) and protein repellency of the conjugate were evaluated.
- NET degradation efficiency was compared between free DNase I and DNase I microgels in biological media.
Main Results:
- DNase I conjugation to microgels preserved enzyme structure and showed high substrate affinity (Km = 0.063 μM).
- DNase I microgels exhibited protein repellency and superior NET degradation compared to free DNase I.
- The conjugate remained effective even with continuous NET release from stimulated neutrophils.
Conclusions:
- Conjugating DNase I to non-fouling microgels creates a stable, active biohybrid platform.
- This platform can serve as an active coating for blood-contacting surfaces to prevent NET-mediated thrombosis and inflammation.
