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Objective <p>This study aimed to systematically evaluate the preclinical evidence on the therapeutic efficacy and underlying mechanisms of hydrogen-delivering biomaterial carriers in the treatment of diabetic foot ulcer (DFU).</p> Method <p>We conducted a comprehensive search across eight databases (PubMed, Web of Science, Embase, Cochrane Library, CBM, CNKI, Wanfang, and VIP) to identify randomized animal studies investigating biomaterial-based hydrogen delivery for DFUs from database inception through November 2025. After screening, eleven studies met inclusion criteria and were included in the final meta-analysis. Data synthesis and statistical analyses were performed using RevMan 5.4; risk of bias was assessed using the SYRCLE’s tool for animal studies.</p> Results <p>The delivery of hydrogen via biomaterial carriers effectively promotes diabetic wound repair by enhancing wound closure rates, stimulating angiogenesis, and improving collagen deposition. Smart delivery systems, such as hydrogen-generating hydrogels, responsive microneedle patches, and photocatalytic dressings, enabled spatiotemporally controlled, sustained H₂ release. This modulation effectively attenuated oxidative stress and suppressed pro-inflammatory cytokine expression (e.g., TNF-α, IL-6). Collectively, biomaterial-mediated hydrogen delivery confers dual therapeutic actions: direct promotion of tissue regeneration and dynamic reprogramming of the impaired wound microenvironment, supporting its potential as a targeted, mechanism-informed intervention for DFUs.</p> Conclusion <p>Biomaterial-based hydrogen delivery systems demonstrate multifaceted therapeutic benefits in preclinical DFU models, primarily through anti-inflammatory, pro-angiogenic, and collagen-enhancing mechanisms. The emergence of smart delivery systems enables localized, tunable, and prolonged hydrogen release, which improves bioavailability and therapeutic precision. Future research should prioritize optimization of release kinetics, pharmacokinetic–pharmacodynamic modeling in diabetic wound beds, and exploration of synergistic combinations (e.g., with growth factors or antimicrobial agents) to advance toward clinically translatable, precision wound therapeutics.</p>

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Hydrogen-delivering biomaterial carriers for diabetic foot ulcer healing: a systematic review and meta-analysis of preclinical animal studies

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月16日

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  • Xiaona Wang,
  • Lei Pan,
  • Haijun Shen

摘要

Objective

This study aimed to systematically evaluate the preclinical evidence on the therapeutic efficacy and underlying mechanisms of hydrogen-delivering biomaterial carriers in the treatment of diabetic foot ulcer (DFU).

Method

We conducted a comprehensive search across eight databases (PubMed, Web of Science, Embase, Cochrane Library, CBM, CNKI, Wanfang, and VIP) to identify randomized animal studies investigating biomaterial-based hydrogen delivery for DFUs from database inception through November 2025. After screening, eleven studies met inclusion criteria and were included in the final meta-analysis. Data synthesis and statistical analyses were performed using RevMan 5.4; risk of bias was assessed using the SYRCLE’s tool for animal studies.

Results

The delivery of hydrogen via biomaterial carriers effectively promotes diabetic wound repair by enhancing wound closure rates, stimulating angiogenesis, and improving collagen deposition. Smart delivery systems, such as hydrogen-generating hydrogels, responsive microneedle patches, and photocatalytic dressings, enabled spatiotemporally controlled, sustained H₂ release. This modulation effectively attenuated oxidative stress and suppressed pro-inflammatory cytokine expression (e.g., TNF-α, IL-6). Collectively, biomaterial-mediated hydrogen delivery confers dual therapeutic actions: direct promotion of tissue regeneration and dynamic reprogramming of the impaired wound microenvironment, supporting its potential as a targeted, mechanism-informed intervention for DFUs.

Conclusion

Biomaterial-based hydrogen delivery systems demonstrate multifaceted therapeutic benefits in preclinical DFU models, primarily through anti-inflammatory, pro-angiogenic, and collagen-enhancing mechanisms. The emergence of smart delivery systems enables localized, tunable, and prolonged hydrogen release, which improves bioavailability and therapeutic precision. Future research should prioritize optimization of release kinetics, pharmacokinetic–pharmacodynamic modeling in diabetic wound beds, and exploration of synergistic combinations (e.g., with growth factors or antimicrobial agents) to advance toward clinically translatable, precision wound therapeutics.