Functionalized peptide hydrogels: enabling dynamic stage-adaptive modulation for wound healing.

Functionalized peptide hydrogels represent an emerging class of intelligent wound dressings that dynamically coordinate the multifaceted process of wound healing through stage-specific bioactivities. By leveraging programmable molecular designs, these hydrogels actively engage with key healing phases-hemostasis, antibiosis, inflammation resolution, angiogenesis, and tissue remodeling-enabling spatiotemporal control over cellular behaviors and molecular cues. For instance, antimicrobial peptides (e.g., EPL, LL37, TCP-25) not only eradicate pathogens but also modulate macrophage polarization to mitigate excessive inflammation. Angiogenic factors (e.g., VEGF, SDF-1) are sustainably released to promote vascularization, while MMP-responsive components facilitate ECM remodeling by balancing collagen deposition and degradation. Additionally, integrin-binding motifs (e.g., RGD) enhance cell adhesion and migration, further accelerating re-epithelialization. With inherent self-healing, injectability, and microenvironmental responsiveness (e.g., to pH, enzymes, or ROS), these hydrogels adapt to dynamic wound conditions, offering synergistic therapeutic outcomes. Future directions include designing multi-stimuli-responsive systems, personalized peptide sequences, and advanced delivery platforms (e.g., 3D-printed scaffolds, cell/exosome-loaded hydrogels) to advance clinical translation in precision wound management and regenerative medicine.