ReviewDiabetology & metabolic syndrome2026
Hydrogen-delivering biomaterial carriers for diabetic foot ulcer healing: a systematic review and meta-analysis of preclinical animal studies.
Review in Diabetology & metabolic syndrome, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Authors and funding
3 authors.
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Abstract
objectiveThis 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).
methodWe 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.
resultsThe 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.
conclusionBiomaterial-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.
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