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

TL;DR

Functionalized peptide hydrogels are smart wound dressings that adapt to different healing stages, improving recovery through targeted biological activities.

Contribution

The paper introduces programmable peptide hydrogels that dynamically modulate wound healing phases with stage-specific bioactivities.

Findings

Antimicrobial peptides like EPL and LL37 reduce pathogens and inflammation by modulating macrophage polarization.

Angiogenic factors such as VEGF and SDF-1 are released to promote vascularization and tissue repair.

Integrin-binding motifs like RGD enhance cell adhesion and migration, accelerating re-epithelialization.

Abstract

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.

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