Sequential drug-release microsphere system for scarless wound healing.

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Wound Healing Research

Background:

• Dynamic imbalance in skin wound healing contributes to hypertrophic scar (HS) formation.
• Current treatments lack comprehensive intervention across all healing stages, hindering scarless outcomes.
• Targeting specific stages inadequately addresses the complex pathology of HS development.

Purpose of the Study:

• To develop a chronologically adaptive drug delivery system for comprehensive wound healing intervention.
• To achieve scarless wound healing by orchestrating sequential release of therapeutic agents.
• To investigate the efficacy of a methacrylylated gelatin (GelMA)-based microsphere system (G/E/T) for HS treatment.

Main Methods:

• Development of a GelMA-based microsphere delivery system (G/E/T) for sequential release of epigallocatechin gallate (EGCG) and triamcinolone acetonide (TA).
• In vitro evaluation of the G/E/T system's impact on oxidative stress, inflammation, and fibroblast activity.
• In vivo validation using mouse full-thickness wound and rabbit ear hypertrophic scar models.

Main Results:

• The G/E/T microsphere system demonstrated precise, stage-specific therapeutic action.
• In vitro studies confirmed alleviation of early-stage oxidative stress and inflammation.
• Persistent inhibition of late-stage fibroblast proliferation and migration was observed, leading to remarkable scarless healing outcomes in vivo.

Conclusions:

• The developed G/E/T system provides a novel strategy for scarless wound healing through sequential drug release and dual-agent synergy.
• This "sequential release and dual-agent synergy" paradigm offers an innovative approach for complex pathological processes.
• The study establishes a framework for developing advanced sequential multidrug delivery systems.