Attaining scalable storage-expansion dualism for bioartificial tissues

TL;DR

This paper introduces a biochemical space-based approach for designing non-toxic cryoprotectants that inhibit ice crystal growth, enabling scalable and safe cryopreservation of bioartificial tissues across various temperatures.

Contribution

It develops an analytic formalism for ice crystal inhibition using molecular topology and identifies chemical spaces for effective, low-toxicity cryoprotective agents.

Findings

Identified distinct regions in chemical space for anti-freeze glycoproteins.

Validated the robustness of the model across different protein classes.

Proposed a molecular design framework for non-cytotoxic cryoprotectants.

Abstract

The untenable dependence of cryopreservation on cytotoxic cryoprotectants has motivated the mining of biochemical libraries to identify molecular features marking cryoprotectants that may prevent ice crystal growth. It is hypothesized that such molecules may be useful across all temperatures eliminating cellular destruction due to equilibration cytotoxicity before and after cryopreservation. By probing the biochemical space using solvation-associated molecular topology and partition-distribution measures we developed an analytic formalism for ice crystal inhibition. By probing the union between a heat-shock protein cluster and an anti-freeze glycoprotein cluster, the model development process generated distinct regions of interest for anti-freeze glycoprotein and proved robust across different classes of proteins. These results confirm that there is a chemical space within which efficacious Ice Crystal Inhibitor molecular libraries can be constructed. These spaces contain latent projections drawn from solvent accessibility, hydrogen bonding capacity and molecular geometry. They also showed that molecular design can be a useful tool in the development of new-age cryoactive matrices to enable the smooth transition across culture, preservation and expansion. These chemical spaces provide low cytotoxicity since such amphipathic molecules occupy a continuum between solubizing and membrane stabilizing regions as shown by the free energy of translocation calculations. These biochemical design spaces are fundamentally the solution to efficient scale-up and deployment of cell therapies. Consequently, this article proposes the use of a molecular knowledge-mining approach in the development of a class of non-cytotoxic cryoprotective agents in the class of Ice Crystal Inhibitor compatible with continuous cryothermic and normothermic cell storage and expansion.