Matrix metalloproteinase-triggered self-assembling peptides for biomedical applications.

Matrix metalloproteinases (MMPs) play critical roles in numerous physiological processes and are essential for various fundamental biological activities. Alterations in their expression levels have been associated with multiple diseases and pathological conditions. The self-assembly of small-molecule peptides into hydrogels and nanomaterials has been widely investigated for its various biomedical applications. MMPs can trigger enzyme-instructed assemblies of peptides with specific sequences to form various hydrogels for potential applications in treating several diseases, including cancer, inflammation, wound healing, myocardial infarction, and central nervous system disease, and in tissue engineering. In addition, MMPs can also trigger the self-assembly of peptides into a variety of nanostructures tailored on demand, especially serving as indicators and activators to increase their functionality in sensing applications and controlled substance release, acting as primitive biological triggers, modulating biological responses, ensuring the targeted delivery of biomolecules to specific locations, and inducing changes in the self-assembled peptide nanostructures by introducing enzyme cleavage site recognition sequences to release loaded drugs, which is crucial for applications in hydrogels and nanomaterials. This review summarizes and highlights the successful applications of various MMP-triggered self-assembled peptide hydrogels and nanostructures over the past decade and emphasizes their potential for controlled drug delivery, targeted therapy, and intelligent biomaterial-assisted wound regeneration and healing. Furthermore, future opportunities and challenges in this field are reviewed.