Screening biomaterials for functional complement activation in serum.

Area of Science:

• Biomaterials Science
• Immunology
• Medical Device Engineering

Background:

• The complement system is crucial for immunity but can be inappropriately activated by medical device biomaterials.
• This inappropriate activation, via classical or alternative pathways, can lead to adverse host or device effects.
• Existing screening methods may not fully capture functional complement activation by biomaterials.

Purpose of the Study:

• To describe and validate methods for screening biomaterials for functional whole complement activation.
• To specifically assess activation of the classical and alternative complement pathways.
• To confirm functional test results using pathway-specific complement activation markers.

Main Methods:

• Utilizing normal human serum for whole complement activation screening.
• Employing C4-deficient guinea pig serum for specific alternative pathway assessment.
• Combining sera and detecting complement markers C4d (classical) and Bb (alternative).
• Following established American Society for Testing and Materials (ASTM) protocols (F1984, F2065, F2567).

Main Results:

• Demonstrated dose- and time-dependent complement activation on example biomaterials like beaded agarose, cellulose acetate, and alginate.
• Confirmed functional complement activation through detection of classical (C4d) and alternative (Bb) pathway markers.
• Showcased significant differences in functional endpoints indicating specific complement pathway activation.

Conclusions:

• Functional whole complement activation assays are appropriate for screening medical device biomaterials.
• These methods can identify biomaterials that may cause adverse events upon implantation or blood contact.
• Accurate screening is essential for developing safer blood-contacting medical devices.