Properties and Characterization of Cryogels: Structural, Mechanical, and Functional Insights

Abstract

Cryogels are a distinct class of macroporous polymeric materials formed through cryopolymerization, where precursor monomers and polymers undergo polymerization and cross-linking under freezing conditions. Unlike conventional hydrogels, which exhibit nanoscale porosity and are synthesized at ambient temperatures, cryogels feature interconnected micrometer-sized pores that confer unique mechanical, structural, and functional properties. Their high porosity, rapid hydration, and efficient mass transport make them highly desirable for tissue engineering, biosensing, drug delivery, and environmental remediation applications. However, a critical challenge remains a comprehensive understanding of the intricate relationships among synthesis parameters, microstructure, and functional performance. This review provides a systematic discussion of cryogel properties, with a focus on their mechanical resilience, biocompatibility, and shape recovery behavior. We examine recent advancements in characterization techniques, including in situ imaging, advanced rheological assessments, and machine learning-assisted porosity evaluation, which have significantly improved our ability to assess cryogel performance. Additionally, we review the biophysical characterization of cryogels composed of different polymer systems, elucidating structure-property correlations in pore architecture and cellular interactions. Expanding beyond traditional biomedical applications, we briefly describe the emerging potential of cryogels in biosensors, soft robotics, and environmental sustainability, emphasizing the importance of an integrated approach that links the structure to functional outcomes. By providing a detailed discussion of established and cutting-edge characterization methodologies, this perspective is a valuable resource for researchers striving to develop next-generation cryogels with precisely tailored properties for specialized applications.

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Diagrammatic rendering of the process of cryogel formation.

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Cryogel pore structure imaged using various techniques. (A) Images of hydrated cryogel by ESEM adapted or reprinted in part with permission from cited ref. Copyright [2005/Royal Society of Chemistry]. (B) 3D reconstruction of the μCT images of poly­(HEMA)-cryogel reproduced with permission from cited ref. Copyright [2005/Royal Society of Chemistry]. (C) Optical image of 5% w/v poly­(N-isopropylacrylamide) (PNiPAAm)-chitosan cryogel; (D) 2D confocal image of 5% w/v polyacrylamide (PAAm) cryogel stained by eosin.

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Porosity and permeability of cryogels are dependent upon the starting monomer concentration. The figure shows PAAm cryogels made using the indicated monomer concentrations with different monomer to cross-linker ratios of acrylamide/methylene bis-acrylamide (AAm/MBAAm ratios) (■4:1; □ 5:1)). Adapted or reprinted in part with permission from cited ref. Copyright [2019/John Wiley and Sons].

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Swelling and deswelling of poly­(NiPAAm) gels over time. Water uptake capacity was measured at regular time intervals for (A) poly­(NiPAAm) cryogel and (C) poly­(NiPAAm) hydrogel. Water retention capacity was quantified at regular time intervals for (B) poly­(NiPAAm) cryogel and (D) poly­(NiPAAm) hydrogel. Gel concentrations were varied: 6, 7, and 8% and the respective cryogel and hydrogel were characterized. Note the difference in swelling rate of cryogels in A is in minutes, while hydrogels in B take hours to reach equilibrium. Adapted or reprinted in part with permission from cited ref. Copyright [2007/Elsevier].

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Temperature-responsive swelling characteristics of poly NiPAAm-HEMA-dextran cryogels. (A) Equilibrium swelling degree of poly NiPAAm-HEMA-dextran cryogels at varied temperatures. (B) Swelling–deswelling kinetics of poly NiPAAm-HEMA-dextran in response to temperature in water. Adapted or reprinted in part with permission from cited ref. Copyright [2013/Taylor & Francis].

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Storage modulus of cryogels vs concentration at 0.5 Hz (red) and 10 Hz (black) for PVA-A (a), PVA-B (b), and PVA-C (c) made using 1 and 3 freeze thaw cycles, respectively, at concentrations of 10, 15, 17.5, and 20% w/w. Note that PVA-C shows a higher storage modulus than PVA-B for the same concentrations. Error bars show 95% confidence intervals (n = 6). Adapted or reprinted in part from cited reference with permission. Copyright [2021/Elsevier].

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Mechanical properties of cryogels. (A–C) Images of the water-swelled chitosan hybrid micronanofiber (CMNF) cryogel for shape recovery after compression, Photograph courtesy of Luhe et al., Copyright 2023 (D, E) Stress–strain curves of the CMNF with 97% strain (50 cycles) and 60% strain (3200 cycles). Adapted or reprinted in part with permission from cited ref. Copyright 2023/American Chemical Society.

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Schematic representation of the cryoprinting method (redrawn inspired by cited reference).