Antibacterial conductive self-healing hydrogel wound dressing with dual dynamic bonds promotes infected wound healing

Abstract

In clinical applications, there is a lack of wound dressings that combine efficient resistance to drug-resistant bacteria with good self-healing properties. In this study, a series of adhesive self-healing conductive antibacterial hydrogel dressings based on oxidized sodium alginate-grafted dopamine/carboxymethyl chitosan/Fe³⁺ (OSD/CMC/Fe hydrogel)/polydopamine-encapsulated poly(thiophene-3-acetic acid) (OSD/CMC/Fe/PA hydrogel) were prepared for the repair of infected wound. The Schiff base and Fe³⁺ coordination bonds of the hydrogel structure are dynamic bonds that can be repaired automatically after the hydrogel network is disrupted. Macroscopically, the hydrogel exhibits self-healing properties, allowing the hydrogel dressing to adapt to complex wound surfaces. The OSD/CMC/Fe/PA hydrogel showed good conductivity and photothermal antibacterial properties under near-infrared (NIR) light irradiation. In addition, the hydrogels exhibit tunable rheological properties, suitable mechanical properties, antioxidant properties, tissue adhesion properties and hemostatic properties. Furthermore, all hydrogel dressings improved wound healing in the infected full-thickness defect skin wound repair test in mice. The wound size repaired by OSD/CMC/Fe/PA3 hydrogel + NIR was much smaller (12%) than the control group treated with Tegaderm™ film after 14 days. In conclusion, the hydrogels have high antibacterial efficiency, suitable conductivity, great self-healing properties, good biocompatibility, hemostasis and antioxidant properties, making them promising candidates for wound healing dressings for the treatment of infected skin wounds.

Keywords: Dynamic crosslinking; Infected wound; Photothermal antibacterial; Self-healing; Wound healing.

Graphical abstract

Fig. 1

a) Preparation scheme of oxidized sodium alginate-grafted dopamine (OSD) and b) polydopamine-coating poly(thiophene-3-acetic acid) (PA); c) Preparation and application of OSD/carboxymethyl chitosan/Fe³⁺/PA (OSD/CMC/Fe/PA) hydrogels.

Fig. 2

a) Photographs pictures of hydrogel formation. Scale bar: 2 cm; b) Modulus of hydrogels, the scanning time for each group is 300 s; c) SEM images of hydrogels; d) Swelling ratio and e) degradation of hydrogels in PBS with at 37 °C, pH = 7.4; f) Conductivity of hydrogels.

Fig. 3

Self-healing properties of OSD/CMC/Fe/PA3 hydrogel. a) Self-healing demonstration and possible mechanisms of microscopic healing in hydrogels. Scale bar: 1 cm; b) Fracture point testing of the hydrogel; c) Self-healing test of the hydrogel.

Fig. 4

a) DPPH clearance ratios of different hydrogels; b) Schematic diagram of pigskin adhesion experiment of hydrogels; c) Adhesion strength of pigskin with hydrogel; d) Hemostatic properties of gelatin sponge, OSD/CMC, OSD/CMC/Fe and OSD/CMC/Fe/PA3; e) Schematic diagram of rat liver hemorrhage model; f) Coagulation properties of gauze and hydrogels; g) Hemolytic activity test results of hydrogels; h) Hydrogel hemolytic activity test graphs; i) The cytocompatibility of these hydrogels was assessed by the viability of L929 cells in the hydrogel leachate; j) LIVE/DEAD staining of L929 cells after 24 h of leachate incubation. *P < 0.05, **P < 0.01, ***P < 0.001.

Fig. 5

Heat maps of a1) OSD/CMC, a2) OSD/CMC/Fe, a3) OSD/CMC/Fe/PA1, a4) OSD/CMC/Fe/PA3 and a5) OSD/CMC/Fe/PA5 hydrogels after 10 min of 808 nm NIR radiation; b) ΔT-NIR radiation time curve of the hydrogel under 1.4 W cm⁻² 808 nm NIR light irradiation; c) Temperature change (ΔT)-irradiation cycle curves of OSD/CMC/Fe/PA3 hydrogels at 1.4 W cm⁻² light intensity of 808 nm NIR light; d) In vitro antibacterial photographs of hydrogels irradiated with NIR light for 0, 1, 3, 5 and 10 min; e) Killing ratio of MRSA and f) E. coli for different irradiation time; g) In vivo antibacterial results of hydrogels. *P < 0.05, **P < 0.01, ***P < 0.001.

Fig. 6

a) Wound pictures of control group (Tegaderm™ film dressing), OSD/CMC hydrogel, OSD/CMC/Fe/PA3 hydrogel and OSD/CMC/Fe/PA3 hydrogel + NIR on day 3, 7 and 14; b) Schematic diagram of the wound area of b1) control, b2) OSD/CMC hydrogel, b3) OSD/CMC/Fe/PA3 hydrogel, and b4) OSD/CMC/Fe/PA3 hydrogel + NIR for 14 days; c) Wound area of each group; d) Thickness of granulation tissue (orange arrow) in different groups on day 14. *P < 0.05, **P < 0.01, ***P < 0.001.

Fig. 7

a) Pictures of histological analysis of wound regeneration on day 3, 7 and 14 of control group (Tegaderm™ film dressing), OSD/CMC hydrogel group, OSD/CMC/Fe/PA3 hydrogel group and OSD/CMC/Fe/PA3 hydrogel + NIR group; b) Statistical graph of angiogenesis on day 7; c) Statistical graph of hair follicles in different groups on 14th day, *P < 0.05, **P < 0.01, ***P < 0.001.

Fig. 8

Immunofluorescently labeled wound tissue with a) TNF-α (green) on day 3, Scale bar: 50 μm; and b) VEGF (green) on day 7, Scale bar: 100 μm; c) TNF-α and d) VEGF statistical data on the percentage of relative area covered, respectively. For all data, the control group was set at 100%. *P < 0.05, **P < 0.01, ***P < 0.001.