TABLE 1.

The detailed properties of amyloid fibrils and its use in albumin-based hydrogels.

Type	Specific properties	Description
Physical properties	Large aspect ratio	Amyloid fibrils are typically a few nanometres wide (d), while having a length (L) of several tens of micrometres, so it has a large aspect ratio (L/d) (Chiti and Dobson, 2017; Cao and Mezzenga, 2019). Scanning electron microscopic observations of the BSA-based hydrogel constructed by Chiang et al. showed that it was also composed of an amyloid fibrous structure, which also showed a large aspect ratio (Chiang et al., 2020). Meanwhile, this BSA-based hydrogel exhibits a slow-release effect due to its porous structure and hybrid siloxane bridges
	High Young’s modulus	The presence of a densely ordered network of hydrogen bonds in the crossed beta structure, similar to the crystalline region of a polymer, gives the fibrils a Young’s modulus of 2–4 GPa and makes them one of the hardest protein materials (Adamcik et al., 2012). A BSA-based conductive hydrogel prepared by physical cross-linking has excellent mechanical properties (1.61 MPa elastic modulus, 17.66 MJ/m3 toughness, and 5.36 MPa tensile stress) and shows good promise for biomedical applications (Xu et al., 2023)
	High surface hydrophobicity	The fibrillation process often involves the unfolding of the internal structure of the protein, leading to the exposure of more hydrophobic amino acids (Mohammadian et al., 2019; Zhou et al., 2020). The HSA hydrogel was constructed by Ana et al., which has a good hydrophobic drug-binding pocket and can be loaded with various substances (especially for hydrophobic drugs) (Vesković et al., 2022)
	Controlled flexibility	Nanofibers with different flexibility, including flexible, semi-flexible and rigid dimensions, can be prepared by simply adjusting the fibrillation conditions, such as pH, ionic strength, protein concentration, etc (Cao and Mezzenga, 2019; Jirkovec et al., 2021). Injectable redox albumin-based hydrogel with in-situ loaded dihydromyricetin constructed by Deng et al., which shows excellent self-healing property, elasticity and biocompatibility and can be used for drug delivery (such as dihydromyricetin) (Deng et al., 2022)
Chemical properties	Highly tolerant of the environment	Compared to protein monomers, amyloid fibrils are more tolerant of extreme environments such as acid, heat and enzymes. Which is due to the low free energy of the crossed ß-structure and the regular and dense structure (Adamcik and Mezzenga, 2018; Babinchak and Surewicz, 2020). A kind of hydrogel capsules based on HSA developed by Chen et al., which is well tolerated in acidic environments and acts better as a protective layer for MRI probes, providing the prerequisite for more accurate results in complex physiological environments (Xu et al., 2021)
	More active sites	Fibrillation exposes more functional groups in the protein, enhancing their ability to interact with drug molecules. In addition, the ordered ß-sheet arrangement enhances the synergistic effect between amino acids (Bhattacharya et al., 2014; Mohammadian and Madadlou, 2016; Maciążek-Jurczyk et al., 2020). There are numerous drug-binding sites on albumin, two main drug-binding sites for albumin are Sudlow site I and Sudlow site II, and albumin can bind more drugs when these two sites are sufficiently exposed (Rong et al., 2022; Bercea et al., 2023)
Biological properties	Low allergenicity	Protein amyloid fibrils are derived from natural proteins, which are more biocompatible and have a lower probability of causing allergic reactions (Willbold et al., 2021). Amyloid fibrils can be used as building blocks for novel albumin-based hydrogel materials that are biocompatible, low cost and hypoallergenic (Diaz and Missirlis, 2022)
	High biological activity	Compared to protein monomers, some amyloid fibrils have stronger antioxidant and antibacterial activity. Some amino acids have high antioxidant activity, such as cysteine, methionine, tryptophan, tyrosine and phenylalanine, and these amino acids are also often involved in the formation of amyloid fibrils. Tryptophan and phenylalanine are involved in protein fibrillation through p-π stacking (Makin et al., 2005). Albumin amyloid fibrils still retain more bioactive sites of natural albumin and can be used as drug carriers to bind a wide range of biomolecules and drugs (Ong et al., 2019; Kong et al., 2023)
	High cell permeability	The ability of nanoparticles to penetrate cell membranes is closely related to their size, shape and charge, and the rod-like structure of amyloid fibrils facilitates cellular phagocytosis (Albanese et al., 2012; Sokolova et al., 2020)