Bridging polymer chemistry and cryobiology

Abstract

Polymers, especially charged polymers, are the key to a sustainable future, as they have the capability to act as alternatives to plastics, reduce the impact of global warming, and offer solutions to global environmental pollution problems. Biomaterial polymers have proven to be incredibly effective in a multitude of applications, including clinical applications. In the fields of cryobiology and cryopreservation, polymers have emerged as credible alternatives to small molecules and other compounds, yielding excellent results. This review outlines the results of research in the areas of polymer chemistry and cryobiology, which have not been discussed together previously. Herein, we explain how recent polymer research has enabled the development of polymeric cryoprotectants with novel mechanisms and the development of novel methods for the intracellular delivery of substances, such as drugs, using a cryobiological technique called the freeze-concentration effect. Our findings indicate that interdisciplinary collaboration between cryobiologists and polymer chemists has led to exciting developments that will further cell biology and medical research.

Fucose is an essential feature in cryoprotective polysaccharides

“…At very high fucose concentrations (above 80 mol%), PTV enhancement is expected to decline due to a trade-off between fucose and other monomers. UA content in particular also has a beneficial effect on cryoprotective outcome (Figure 4b), as expected from negatively charged monomers (Matsumura et al, 2022), following a linear increasing trend ( R 2 =0.202, N=24) until about 50 mol%, whereas an increase in UA stops generating a meaningful change in PTV. The absence of UA resulted in an average PTV fold-change of 1.0±0.2, indicating that polysaccharides not containing UA are not cryoprotective.…”

“…The metabolic and histological viability of cryopreserved Vero cells was determined in freezing media containing different polysaccharides supplemented with 10% DMSO. It is widely accepted that polyanionicity plays a major role in most biologically active polysaccharides, including cryopreservation (Matsumura et al, 2022). The property is mostly established by the presence of uronic acid (UA) monomers that contain a deprotonated carboxylate moiety at physiological pH (H. M. Wang et al, 1991), but may also be conferred by sulfate, phosphate or other acyl modifiers in the polymer chain.…”

“…Sun et al, 2022), biologically produced antifreeze proteins (AFPs) have excellent cryoprotective performance (Yeh & Feeney, 1996) but their purification and isolation is not cost-effective. Conversely, bio-based polysaccharides produced by microorganisms can leverage a byproduct-based circular economy of added value production (Freitas et al, 2011; Matsumura et al, 2022) that can rival AFP implementation in cryoprotective formulations both in cost and performance (Guerreiro, Silva, Torres, et al, 2021).…”

Cryopreservation in the Era of Cell Therapy: Revisiting Fundamental Concepts to Enable Future Technologies

“…Nevertheless, cells are subjected to significant osmotic and mechanical stress, as well as cryoprotectant toxicity for an extended period of time. [28,29] Although the cooling rate of 1 °C min −1 is most commonly used after it was popularized by Mazur in 1984, [24] systematic research verifying this optimal cooling rate has not yet been carried out. More on this fundamental concept of cryopreservation would be discussed in subsequent sections.…”

“…At the same time, biocompatible materials such as AFPs and hydrogels are also being studied and developed as CPAs. New chemical tools are being developed to address challenges in cryopreservation and describe the complex nature of this multivariate problem, [28,29] in which multiple mechanisms of damage need to be addressed and subtle differences between cell types and freezing methods exist. This section summarizes the mechanisms (Figure 4) and applications of all existing types of CPAs, and highlights their strengths and drawbacks (Table 2).…”