Hyaluronic Acid Aerogels Made Via Freeze–Thaw-Induced Gelation

Abstract

The biodegradability, biocompatibility, and bioactivity of hyaluronic acid (HA), a natural polysaccharide, combined with the low density, high porosity, and high specific surface area of aerogels attract interest for biomedical applications such as wound dressings. In this work, physically cross-linked HA aerogels were prepared via the freeze–thaw (FT) induced gelation method, solvent exchange, and drying with supercritical CO2. The morphology and properties of HA aerogels (volume shrinkage, density, and specific surface area) were investigated as a function of several process parameters: HA concentration, solution pH, number of FT cycles, and type of nonsolvent used during solvent exchange. We demonstrate that the HA solution pH plays a key role in the aerogel formation, as not all conditions result in materials with high specific surface area. HA aerogels were of low density (<0.2 g/cm3), high specific surface area (up to 600 m2/g), and high porosity (≥90%). Scanning electron microscopy pictures revealed that HA aerogels present a porous structure with meso- and small macropores. The results show that HA aerogels are promising biomaterials with tunable properties and internal structure that offer high potential as, e.g., wound dressings.

Exploring the Progress of Hyaluronic Acid Hydrogels: Synthesis, Characteristics, and Wide-Ranging Applications

“…Porous structure, controlled drug release [43,44] Enzymatic cross-linking Horseradish peroxidase, tyramine Tissue engineering, drug delivery, wound healing [45,46] 2.1. Chemical Cross-Linking Chemical cross-linking is a method used to create stable three-dimensional networks in HA hydrogels.…”

“…Freeze-thawing is a physical technique employed for modifying HA hydrogels. The procedure entails placing the HA solution or hydrogel in a freezer, lowering the temperature below freezing point to solidify it [43,106]. Subsequently, the solution or hydrogel is thawed by raising the temperature, usually to room temperature or higher, facilitating the melting process [107].…”

“…Subsequently, the solution or hydrogel is thawed by raising the temperature, usually to room temperature or higher, facilitating the melting process [107]. This freeze-thaw cycle is repeated multiple times, involving the successive freezing and thawing of the hydrogel [43,107]. As a result of this freeze-thaw process, the HA/PVA hydrogels undergo physical transformations, leading to the creation of interconnected networks and modifying their properties [43,44].…”

“…This freeze-thaw cycle is repeated multiple times, involving the successive freezing and thawing of the hydrogel [43,107]. As a result of this freeze-thaw process, the HA/PVA hydrogels undergo physical transformations, leading to the creation of interconnected networks and modifying their properties [43,44]. These alterations can impact the structure, porosity, mechanical strength, and release characteristics of the hydrogel.…”

“…Cryogels synthesized via chemical cross-linking possess a high surface area and easily tunable porosity characteristics. These properties make cryogels well suited for applications such as tissue engineering, drug delivery, wound dressings, and other biomedical uses [43,110].…”