Combinatorial Biomaterials Discovery Strategy to Identify New Macromolecular Cryoprotectants

Area of Science:

• Biomaterials Science
• Cell Biology
• Polymer Chemistry

Background:

• Current cryoprotective agents (CPAs) are often toxic small molecules, limiting cell yield and banking applications.
• Rational design of CPAs is challenging due to a lack of established structure-property relationships.
• There is a critical need for novel, less toxic CPAs for effective cell preservation.

Purpose of the Study:

• To identify novel macromolecular cryoprotectants using a photochemical high-throughput discovery platform.
• To explore the relationship between polymer composition and cryoprotective function.
• To assess the efficacy of identified polymers in reducing the need for traditional CPAs like DMSO.

Main Methods:

• Synthesis of 120 unique polyampholytes via photopolymerization utilizing RAFT agents.
• Utilized liquid handling systems for automated polymer synthesis and screening.
• Cryopreservation screening of synthesized polymers with a nucleated cell line.

Main Results:

• Identified "hit" polymers demonstrating significant cryoprotective activity.
• Observed nonlinear trends between polymer composition and cryoprotective function.
• Discovered polymer aggregation as a critical factor influencing CPA efficacy.
• The most effective polymers reduced the required volume of dimethyl sulfoxide (DMSO) for cell cryopreservation.

Conclusions:

• Photochemical high-throughput screening is a viable approach for discovering macromolecular CPAs.
• Macromolecular CPAs offer a promising alternative to traditional small-molecule agents.
• This strategy has the potential to advance cell banking, storage, and transport technologies.