Sono-enzymatically engineered tannic acid/doxycycline-lignin nanoparticles enable self-assembled bioactive chitosan hydrogels for chronic wound healing
- 1Group of Molecular and Industrial Biotechnology, Department of Chemical Engineering, Universitat Politècnica de Catalunya, Rambla Sant Nebridi, 22, Terrassa, 08222, Spain
- 2Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 25, 1113, Sofia, Bulgaria
- 3Unitat de Ferides Complexes, Consorci Sanitari de Terrassa Hospital de Terrassa, Ctra. Torrebonica, s/n, 08227, Terrassa, Spain
Abstract
Chronic wounds remain a major clinical challenge due to their multifactorial pathology, characterised by excessive proteolytic and oxidative enzyme activity, persistent inflammation, bacterial infection, and biofilm formation. Here, we report a green, nano-enabled hydrogel fabricated through the in situ self-assembly of thiolated chitosan (TCS), driven by tannic acid/doxycycline-functionalised lignin nanoparticles (PLD NPs). Doxycycline was incorporated at a sub-inhibitory concentration (12.5 μg/mL), enabling PLD NPs (0.5 mg/mL) to inhibit matrix metalloproteinase (MMP) activity by approximately 50 % without inducing antibacterial effects. Dynamic interactions between the polymer network and NPs produced injectable, self-healing hydrogels capable of stimuli-responsive NPs release under chronic wound-like conditions, including variations in pH, hydrogen peroxide, and lysozyme. Ex vivo evaluation using human chronic wound exudates demonstrated potent inhibition of MMP and myeloperoxidase activities by 73 % and 80 %, respectively. The hydrogels further exhibited strong antimicrobial and antibiofilm activity against Staphylococcus aureus and Pseudomonas aeruginosa, achieving 4.8- and 4.3-log reductions in bacterial viability while preventing 73 % and 65 % of biofilm formation, respectively. In vitro studies confirmed excellent biocompatibility with human keratinocytes and fibroblasts, together with up to 82 % cellular antioxidant activity and enhanced fibroblast migration. Importantly, in an in vivo full-thickness S. aureus-infected mouse wound model, the hydrogels achieved complete wound closure within 18 days, outperforming commercial antiseptic treatments. Overall, this work demonstrates a multifunctional hydrogel platform that simultaneously modulates the chronic wound microenvironment, controls infection and biofilm formation, reduces oxidative stress, and promotes tissue regeneration, offering a promising strategy for advanced chronic wound management.
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BibTeX
@article{ahmadi2026sonoenzymatically,
title = {{Sono-enzymatically engineered tannic acid/doxycycline-lignin nanoparticles enable self-assembled bioactive chitosan hydrogels for chronic wound healing}},
author = {Reza Ahmadi and Eva Ramon and Katerina Todorova and Zdravka Petrova and Dolores Hinojosa-Caballero and Tzanko Tzanov},
journal = {Materials Today Bio},
year = {2026},
month = oct,
doi = {10.1016/j.mtbio.2026.103792},
url = {https://doi.org/10.1016/j.mtbio.2026.103792},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Sono-enzymatically engineered tannic acid/doxycycline-lignin nanoparticles enable self-assembled bioactive chitosan hydrogels for chronic wound healing
AU - Reza Ahmadi
AU - Eva Ramon
AU - Katerina Todorova
AU - Zdravka Petrova
AU - Dolores Hinojosa-Caballero
AU - Tzanko Tzanov
PY - 2026
DA - 2026/10/28
JO - Materials Today Bio
DO - 10.1016/j.mtbio.2026.103792
UR - https://doi.org/10.1016/j.mtbio.2026.103792
AB - Chronic wounds remain a major clinical challenge due to their multifactorial pathology, characterised by excessive proteolytic and oxidative enzyme activity, persistent inflammation, bacterial infection, and biofilm formation. Here, we report a green, nano-enabled hydrogel fabricated through the in situ self-assembly of thiolated chitosan (TCS), driven by tannic acid/doxycycline-functionalised lignin nanoparticles (PLD NPs). Doxycycline was incorporated at a sub-inhibitory concentration (12.5 μg/mL), enabling PLD NPs (0.5 mg/mL) to inhibit matrix metalloproteinase (MMP) activity by approximately 50 % without inducing antibacterial effects. Dynamic interactions between the polymer network and NPs produced injectable, self-healing hydrogels capable of stimuli-responsive NPs release under chronic wound-like conditions, including variations in pH, hydrogen peroxide, and lysozyme. Ex vivo evaluation using human chronic wound exudates demonstrated potent inhibition of MMP and myeloperoxidase activities by 73 % and 80 %, respectively. The hydrogels further exhibited strong antimicrobial and antibiofilm activity against Staphylococcus aureus and Pseudomonas aeruginosa, achieving 4.8- and 4.3-log reductions in bacterial viability while preventing 73 % and 65 % of biofilm formation, respectively. In vitro studies confirmed excellent biocompatibility with human keratinocytes and fibroblasts, together with up to 82 % cellular antioxidant activity and enhanced fibroblast migration. Importantly, in an in vivo full-thickness S. aureus-infected mouse wound model, the hydrogels achieved complete wound closure within 18 days, outperforming commercial antiseptic treatments. Overall, this work demonstrates a multifunctional hydrogel platform that simultaneously modulates the chronic wound microenvironment, controls infection and biofilm formation, reduces oxidative stress, and promotes tissue regeneration, offering a promising strategy for advanced chronic wound management.
SN - 2590-0064
ER -