Advances in self-assembling growth factor-mimetic peptides for regenerative medicine

Growth factors (GFs) are signaling molecules that play pivotal roles in tissue engineering by regulating essential biological processes such as cell proliferation, differentiation, migration, and survival. Despite their remarkable therapeutic potential, the clinical translation of natural GFs remains hindered by several intrinsic limitations, such as high production costs, poor stability and short half-life in vivo, insufficient targeted delivery and controlled release capabilities. To address these challenges, increasing attention has been directed toward growth factor-mimetic peptides derived from the bioactive domains of natural GFs. In particular, self-assembling GF-mimetic peptides can spontaneously organize into ordered nanostructures under physiological conditions, enabling enhanced stability, multivalent bioactivity, and localized presentation of signaling motifs while partially recapitulating the functions of native GFs. In this review, we systematically summarize the classification, structural characteristics, and biological functions of self-assembling GF-mimetic peptides and discuss recent advances in incorporating single or multiple GF-derived active epitopes into various biomaterial platforms. We further highlight how the synergistic or additive effects of these multifunctional systems contribute to enhanced tissue repair and regeneration. In addition, this review emphasizes current design strategies for constructing GF-mimetic peptides, focusing on the relationship between molecular design, self-assembly behavior, and bioactivity. Finally, we discuss the current challenges and future perspectives for the development of self-assembling GF-mimetic peptide systems in regenerative medicine.