Abstract
Cryogels obtained by the cryotropic gelation process are macroporous hydrogels with a well-developed system of interconnected pores and shape memory. There have been significant recent advancements in our understanding of the cryotropic gelation process, and in the relationship between components, their structure and the application of the cryogels obtained. As cryogels are one of the most promising hydrogel-based biomaterials, and this field has been advancing rapidly, this review focuses on the design of biodegradable cryogels as advanced biomaterials for drug delivery and tissue engineering. The selection of a biodegradable polymer is key to the development of modern biomaterials that mimic the biological environment and the properties of artificial tissue, and are at the same time capable of being safely degraded/metabolized without any side effects. The range of biodegradable polymers utilized for cryogel formation is overviewed, including biopolymers, synthetic polymers, polymer blends, and composites. The paper discusses a cryotropic gelation method as a tool for synthesis of hydrogel materials with large, interconnected pores and mechanical, physical, chemical and biological properties, adapted for targeted biomedical applications. The effect of the composition, cross-linker, freezing conditions, and the nature of the polymer on the morphology, mechanical properties and biodegradation of cryogels is discussed. The biodegradation of cryogels and its dependence on their production and composition is overviewed. Selected representative biomedical applications demonstrate how cryogel-based materials have been used in drug delivery, tissue engineering, regenerative medicine, cancer research, and sensing.
Highlights
Introduction published maps and institutional affilHydrogels are physically or chemically cross-linked hydrophilic polymer networks, which are capable of retaining large amounts of water without dissolving
It is noteworthy that the presence of a low-molecular-weight chitosan in apple pectin (AP) cryogels inhibits macrophage adhesion and does not induce the activation of the complement system, in contrast to cryogels based on Heracleum pectin (HP)
Hydroxyapatite nanoparticles added to cryogel scaffold produced from silk-fibroin, chitosan, and agarose have been used for the controlled release of growth factors [110]
Summary
Cryotropic gelation is the formation of a hydrogel under semi-frozen conditions, when most of the solvent crystallizes, and gelation occurs in small non-frozen areas around the solvent crystals (Figure 1) [2,6,10]. Water is considered to be the best solvent for the formation of biocompatible cryogels for biomedical applications. Gelation can occur through different mechanisms, usually through the formation of covalent bonds, or physical interactions (ionic bonding, hydrogen bonding and others) [13]. Gels 2021, 7, 79 is the most commonly used method of preparing polymer cryogels. Variation of the cryotropic gelation parameters, such as the freezing temperature, cooling rate, and the presence of the ions or other solutes, as well as the polymer and solvent content, allows the tuning of cryogel properties for a specific application
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