Enhancing the Biological Functionality of Hydrogels Using Self-Assembling Peptides

Hydrogels are ECM-mimicking three-dimensional (3D) networks that are widely used in biomedical applications; however, conventional natural and synthetic polymer-based hydrogels present limitations such as poor mechanical strength, limited bioactivity, and low reproducibility. Self-assembling peptides (SAPs) offer a promising alternative, as they can form micro- and nanostructured hydrogels through non-covalent interactions and allow precise control over their biofunctionality, mechanical properties, and responsiveness to biological cues. Through rational sequence design, SAPs can be engineered to exhibit tunable mechanical properties, controlled degradation rates, and multifunctionality, and can dynamically regulate assembly and degradation in response to specific stimuli such as pH, ionic strength, enzymatic cleavage, or temperature. Furthermore, SAPs have been successfully incorporated into conventional hydrogels to enhance cell adhesion, promote matrix remodeling, and provide a more physiologically relevant microenvironment. In this review, we summarize recent advances in SAP-based hydrogels, particularly focusing on their novel biofunctional properties such as anti-inflammatory, antimicrobial, and anticancer activities, as well as bioimaging capabilities, and discuss the mechanisms by which SAP hydrogels function in biological systems.