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May 4, 2026SHILAP Revista de lepidopterología0 citationsOpen Access

A bioinspired enzyme-responsive hydrogel for spatiotemporal control of macrophage reprogramming in chronic wounds

Key Points

This study aims to evaluate how enzyme-responsive hydrogels influence macrophage behavior and promote wound healing in chronic wounds.
Constructed a comparative dataset from 182 studies, including eight preclinical investigations for analysis.
Focused on hydrogels responsive to matrix metalloproteinases, reactive oxygen species, and cathepsins.
Analyzed the effects on macrophage behavior and healing rates in chronic wound models.
Wound closure rates ranged from 60% to 90% by day 14.
ROS-responsive hydrogels accelerated healing, while MMP-responsive hydrogels provided sustained effects.
Hydrogels with exosomes showed the best healing outcomes, increasing M2 macrophage markers and decreasing pro-inflammatory cytokines.

Abstract

BackgroundChronic wounds remain a significant challenge in healthcare due to persistent inflammation and disrupted macrophage polarization.ObjectiveIn this study, we conducted a quantitative comparative analysis to assess how enzyme-responsive hydrogels influence macrophage behaviour and promote wound healing.MethodsA structured comparative dataset was constructed from 182 screened studies, with eight preclinical investigations included for quantitative analysis, focusing on hydrogels responsive to matrix metalloproteinases (MMP), reactive oxygen species (ROS), and cathepsins.ResultsWound closure rates ranged from 60% to 90% by day 14. ROS-responsive hydrogels accelerated early-stage healing, while MMP-responsive hydrogels provided more sustained effects. Hydrogels containing exosomes produced the best healing outcomes, while those containing nanozymes provided prolonged anti-inflammatory benefits. All hydrogel systems increased M2 macrophage marker expression and reduced pro-inflammatory cytokine levels. We identified key pathways, including redox regulation, extracellular matrix remodelling, and epigenetic mechanisms, that affect macrophage polarization.ConclusionPreclinical results are promising, challenges such as the lack of standardized measurement protocols and limited clinical studies remain. This study offers a data-driven framework for understanding enzyme-responsive hydrogels and identifies priorities for future research.

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