Progress in Self-Assembled Extracellular Matrix Structural Protein Mimetic Peptides: From Rational Design and Assembly Pathways to Biomedical Applications

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The extracellular matrix (ECM) is a critical three-dimensional scaffold that maintains the structural integrity and physiological function of tissues and organs. While native ECM structural proteins like collagen and elastin have been widely studied for their ECM-mimetic properties, their clinical translation faces challenges such as pathogen transmission, immunogenicity, and batch variability. Self-assembling peptides, particularly collagen-mimetic peptides (CMPs) and elastin-like peptides (ELPs), offer a promising alternative due to their reproducibility, low immunogenicity, and tunable properties. Recent advances in peptide design have enabled precise mimicry of the ECM’s composition, hierarchical structure, nanoscale morphology, and biological function. These peptides can controllably self-assemble into nanofibers, hydrogels, and 3D scaffolds that recapitulate key aspects of the native ECM microenvironment, broadening their utility in biomedical applications. This review summarizes progress in the design and application of ECM-mimetic peptides, focusing on their roles in tissue engineering, regenerative medicine, and drug delivery. We also discuss emerging challenges and future directions to advance the field toward clinical implementation.