Dual-Function Hydrogel Dressings with a Dynamic Exchange of Iron Ions and an Antibiotic Drug for Treatment of Infected Wounds.

Bacterial infection is a major problem with diabetic wounds that may result in nonhealing chronic ulcers. Here, we report an approach to antibacterial hydrogel dressings for enhanced treatment of infected skin wounds. A fibrous hydrogel was derived from cellulose nanocrystals that were modified with dopamine and cross-linked with gelatin. The hydrogel was loaded with gentamicin, an antibiotic drug. Enhanced antibacterial hydrogel performance resulted from (i) a highly specific sequestration of Fe3+ ions (much needed by bacteria) from the wound exudate and (ii) a dynamic exchange between gentamicin released from the hydrogel and Fe3+ ions withdrawn from the wound exudate. Such exchange was possible due to the high value of the binding constant of Fe3+ ions to dopamine. The hydrogel did not affect the metabolic activity of skin-related cells and showed enhanced antibacterial performance against common wound pathogens such as S. aureus and P. aeruginosa. Furthermore, it promoted healing of infected diabetic wounds due to a synergistic antibacterial effect providing the dynamic exchange between Fe3+ ions and gentamicin. This work provides a strategy for the design of dual-function wound dressings, with both starving and killing bacteria and enhanced wound healing performance.

[1]  Mengxiao Sun,et al.  A facile and versatile strategy for synthesis of dopamine‐functionalized polymers , 2022, Journal of Polymer Science.

[2]  Shuangyang Li,et al.  Skin-Adaptable, Long-Lasting Moisture, and Temperature-Tolerant Hydrogel Dressings for Accelerating Burn Wound Healing without Secondary Damage. , 2021, ACS applied materials & interfaces.

[3]  D. Cescon,et al.  Microfluidic Arrays of Breast Tumor Spheroids for Drug Screening and Personalized Cancer Therapies , 2021, Advanced healthcare materials.

[4]  N. Annabi,et al.  Rational Design of Immunomodulatory Hydrogels for Chronic Wound Healing , 2021, Advanced materials.

[5]  E. Kumacheva,et al.  Nanofibrillar Hydrogel Recapitulates Changes Occurring in the Fibrotic Extracellular Matrix. , 2021, Biomacromolecules.

[6]  Wei Li,et al.  Adhesive, Self-Healing, and Antibacterial Chitosan Hydrogels with Tunable Two-Layer Structures , 2020 .

[7]  E. Kumacheva,et al.  Nanocolloidal Hydrogel with Sensing and Antibacterial Activities Governed by Iron Ion Sequestration , 2020 .

[8]  A. Urtti,et al.  Thermo- and pH-sensitive glycosaminoglycans derivatives obtained by controlled grafting of poly(N-isopropylacrylamide). , 2020, Carbohydrate polymers.

[9]  R. Pei,et al.  Recent progress of highly adhesive hydrogels as wound dressings. , 2020, Biomacromolecules.

[10]  Meng Li,et al.  Injectable Antimicrobial Conductive Hydrogels for Wound Disinfection and Infectious Wound Healing. , 2020, Biomacromolecules.

[11]  Haifeng Liu,et al.  A resazurin-based, nondestructive assay for monitoring cell proliferation during a scaffold-based 3D culture process , 2020, Regenerative biomaterials.

[12]  C. Weller,et al.  First-Line Interactive Wound Dressing Update: A Comprehensive Review of the Evidence , 2020, Frontiers in Pharmacology.

[13]  Jianhua Zhang,et al.  An Injectable and Tumor-Specific Responsive Hydrogel with Tissue-Adhesive and Nanomedicine-Releasing Abilities for Precise Locoregional Chemotherapy , 2019, Acta biomaterialia.

[14]  Lin Qiu,et al.  pH-Switchable Antimicrobial Nanofiber Networks of Hydrogel Eradicate Biofilm and Rescue Stalled Healing in Chronic Wound. , 2019, ACS nano.

[15]  D. Mooney,et al.  Biomaterials to Mimic and Heal Connective Tissues , 2019, Advanced materials.

[16]  Z. Zhai,et al.  Adaptive antibacterial biomaterial surfaces and their applications , 2019, Materials today. Bio.

[17]  Yubo Fan,et al.  Bacteria-responsive intelligent wound dressing: Simultaneous In situ detection and inhibition of bacterial infection for accelerated wound healing. , 2018, Biomaterials.

[18]  Ali Khademhosseini,et al.  Drug delivery systems and materials for wound healing applications. , 2018, Advanced drug delivery reviews.

[19]  A. Oryan,et al.  Effectiveness of topical application of ostrich oil on the healing of Staphylococcus aureus- and Pseudomonas aeruginosa-infected wounds , 2017, Connective tissue research.

[20]  M. Kamperman,et al.  Reaction Pathways in Catechol/Primary Amine Mixtures: A Window on Crosslinking Chemistry , 2016, PloS one.

[21]  Aurelien Forget,et al.  Antibacterial and Anti-Inflammatory pH-Responsive Tannic Acid-Carboxylated Agarose Composite Hydrogels for Wound Healing. , 2016, ACS applied materials & interfaces.

[22]  Yangyang Han,et al.  Dual Functional Biocomposites Based on Polydopamine Modified Cellulose Nanocrystal for Fe3+-Pollutant Detecting and Autoblocking , 2016 .

[23]  Bruce P. Lee,et al.  Effect of metal ion type on the movement of hydrogel actuator based on catechol-metal ion coordination chemistry , 2016 .

[24]  B. Furman,et al.  Streptozotocin‐Induced Diabetic Models in Mice and Rats , 2015, Current protocols in pharmacology.

[25]  Keming Xu,et al.  Injectable Degradation-Resistant Hyaluronic Acid Hydrogels Cross-Linked via the Oxidative Coupling of Green Tea Catechin. , 2015, ACS macro letters.

[26]  L. Ambrosio.  The role of biomaterials in burn treatment , 2014, Burns & Trauma.

[27]  T. Richards,et al.  The role of iron in the skin and cutaneous wound healing , 2014, Front. Pharmacol..

[28]  S. Percival,et al.  The Effect of pH on the Extracellular Matrix and Biofilms. , 2014, Advances in wound care.

[29]  Henrik Birkedal,et al.  pH-induced metal-ligand cross-links inspired by mussel yield self-healing polymer networks with near-covalent elastic moduli , 2011, Proceedings of the National Academy of Sciences.

[30]  Ruhong Zhou,et al.  Urea denaturation by stronger dispersion interactions with proteins than water implies a 2-stage unfolding , 2008, Proceedings of the National Academy of Sciences.

[31]  Bruce P. Lee,et al.  A reversible wet/dry adhesive inspired by mussels and geckos , 2007, Nature.

[32]  M. Stacey,et al.  Iron and 8-isoprostane levels in acute and chronic wounds. , 2003, The Journal of investigative dermatology.

[33]  K. Scharffetter-Kochanek,et al.  Selective pick-up of increased iron by deferoxamine-coupled cellulose abrogates the iron-driven induction of matrix-degrading metalloproteinase 1 and lipid peroxidation in human dermal fibroblasts in vitro: a new dressing concept. , 2001, The Journal of investigative dermatology.