Ice Templating Soft Matter: Fundamental Principles and Fabrication Approaches to Tailor Pore Structure and Morphology and Their Biomedical Applications

Abstract

Porous scaffolds are widely used in biomedical applications where pore size and morphology influence a range of biological processes, including mass transfer of solutes, cellular interactions and organization, immune responses, and tissue vascularization, as well as drug delivery from biomaterials. Ice templating, one of the most widely utilized techniques for the fabrication of porous materials, allows control over pore morphology by controlling ice formation in a suspension of solutes. By fine-tuning freezing and solute parameters, ice templating can be used to incorporate pores with tunable morphological features into a wide range of materials using a simple, accessible, and scalable process. While soft matter is widely ice templated for biomedical applications and includes commercial and clinical products, the principles underpinning its ice templating are not reviewed as well as their inorganic counterparts. This review describes and critically evaluates fundamental principles, fabrication and characterization approaches, and biomedical applications of ice templating in polymer-based biomaterials. It describes the utility of porous scaffolds in biomedical applications, highlighting biological mechanisms impacted by pore features, outlines the physical and thermodynamic mechanisms underpinning ice templating, describes common fabrication setups, critically evaluates complexities of ice templating specific to polymers, and discusses future directions in this field.

High‐Yield of Nucleic Acid Adsorption via Poly(Vinyl Alcohol‐co‐Ethylene) Nanofiber‐Based Anion‐Exchange Chitosan Aerogel Membrane with Controllable Porosity

“…Faster freezing rate leads to smaller pore size, which is matched with the conclusion from previous work. [ 22 ] The fast solidification process of two different molecules, namely water and isopropanol, leads to multidirectional freezing and forms various spatial shapes as shown in Figure 2c; meanwhile the slow solidification process leads to unidirectional freezing and forms a ladder‐like pore shape as shown in Figure 2g. Several gullies are observed on the surface of the membrane (−20 °C), which is due to the formation of amorphous regions between solvent crystal zones.…”

“…[ 19,20 ] Among numerous porous aerogels for adsorbents, chitosan (CS) aerogel with high porosity, large specific surface area, and biocompatibility is particularly suitable for the adsorption of biomolecules in comparison to synthetic materials. [ 21 ] By controlling the condition of the gelation process (freezing temperature and solution viscosity), pore size and morphology of chitosan aerogel can be intentionally tailored, [ 22–24 ] in which the large surface area of aerogels is modified with different functional groups such as imide, [ 25 ] amine, [ 21,24 ] methyl, [ 26 ] and carbamate [ 27 ] for various applications of molecular adsorption. Therein, the cellulose‐based chitosan aerogel has widely been studied in the field of purification and separation of proteins, [ 28,29 ] whereas cellulose‐based chitosan adsorbents have to be modified with ligands in a relatively low adsorption efficiency and capacity, which have hindered large‐scale application in biomolecule adsorption.…”

Bone tissue engineering using 3D silk scaffolds and human dental pulp stromal cells epigenetic reprogrammed with the selective histone deacetylase inhibitor MI192

“…Moreover, these scaffolds exhibited a thin sheet-like lamellae network, where increasing the silk concentration resulted in thicker lamellae. This is expected as more ice crystals form within the negative cast of the pores during the fabrication process, thus displacing the silk dissolved in the solution and creating a concentrated silk layer surrounding the fully formed crystal (Joukhdar et al 2021). Hence, the increased lamellae thickness of the 5 wt% scaffold can be attributed to an increased quantity of silk available to concentrate around the ice crystals during fabrication.…”

Vertical Extrusion Cryo(bio)printing for Anisotropic Tissue Manufacturing

“…[10,11] In particular, ice-templating, one of the most widely utilized techniques for the fabrication of materials with anisotropic microchannels, allows control over pore morphologies by controlling directional ice formation in a suspension of solute(s). [12][13][14][15] During the freezing process, ice crystals form and propagate through a set direction within the biomaterial solution. When the construct cross-links and thaws, the melted ice crystals form interconnected anisotropic microchannels within the scaffold.…”