Ion-complementary self-assembling peptides have been studied in many fields for their distinct advantages, mainly due to their self-assembly properties. However, their shortcomings, such as insufficient specific activity and poor mechanical properties, also limited their application. For the better and wider application of these promising biomaterials, ion-complementary self-assembling peptides can be modified with their self-assembly properties not being destroyed to the greatest extent. The modification strategies were reviewed by taking RADA16-I as an example. For insufficient specific activity, RADA16-I can be structurally modified with active motifs derived from the active domain of the extracellular matrix or other related active factors. For weak mechanical properties, materials with strong mechanical properties or that can undergo chemical crosslinking were used to mix with RADA16-I to enhance the mechanical properties of RADA16-I. To improve the performance of RADA16-I as drug carriers, appropriate adjustment of the RADA16-I sequence and/or modification of the RADA16-I-related delivery system with polymer materials or specific molecules can be considered to achieve sustained and controlled release of specific drugs or active factors. The modification strategies reviewed in this paper may provide some references for further basic research and clinical application of ion-complementary self-assembling peptides and their derivatives.
Keywords: active motifs modification; hydrogel; regenerative medicine; self-assembling peptide.