Alginate-Based Cryogels for Combined Chemo/Photothermal Antibacterial Therapy and Rapid Hemostasis

Abstract

As novel wound dressings, cryogels with rapid hemostatic property and good sterilization effect are urgently desirable for wound healing. To reduce the use of antibiotics, antibacterial photothermal therapy with broad-spectrum bactericidal capacity and non-obvious bacterial resistance has been widely researched. However, photothermal agents usually suffer from poor hemostatic ability. In this research, sodium alginate (SA) and epigallocatechin gallate (EGCG) were non-covalently cross-linked in suit by ferric ions to obtain SA/EGCG/Fe (SEF) cryogels after lyophilization as an antibacterial wound dressing. Next, its photothermal performance was intensively assessed. Moreover, its hemostasis and bactericidal effect were evaluated. First, it displayed extraordinary photothermal ability owing to the formation of Fe³⁺/EGCG-based metal phenolic networks (MPNs) inside the SEF cryogel. Furthermore, in vitro and in vivo assays illustrated that it exhibits rapid hemostatic capacity owing to its high porosity and MPN-mediated cell adhesion capacity. In conclusion, the SEF cryogel manifests satisfactory hemostatic and bactericidal properties. Therefore, it is a promising wound-dressing candidate for clinical applications.

Scheme 1. Schematic Illustration of the Alginate-Based Cryogel and Its Application as a Combined Chemo/Photothermal Antibacterial Wound Dressing

Figure 1

(a) FTIR spectrometry of SA, EGCG, and SEF(0.75). (b) Photographs of cryogels and hydrogels. (c) Morphology of gauze and cryogels determined by SEM. Scale bar: 200 and 50 μm.

Figure 2

(a) Storage modulus (G′) and loss modulus (G″) curves of hydrogels. (b) Water absorption rates and (c) porosity rates of cryogels. (d) Release of EGCG from SEF(0.75) at pH 5.5 and 7.4.

Figure 3

(a) Infrared thermal images of SF and SEF(0.75) cryogels under NIR irradiation (808 nm, 0.5 W/cm²) at different time points. Temperature changes of cryogel aqueous solutions under NIR laser irradiation (b) treated with different cryogels (808 nm, 0.5 W/cm², 10 min), (c) at different power densities [SEF(0.75)]. (d) Heating and cooling curves of the SEF(0.75) aqueous solution over 10 cycles of irradiation (808 nm, 0.5 W/cm², 10 min). (e) Time constant obtained by applying the linear fit of time from the cooling period vs −ln (θ).

Figure 4

Antibacterial rates of (a) S. aureus and (b) E. coli after different treatments.

Figure 5

Confocal laser scanning microscopy images of (a) S. aureus and (b) E. coli, where dead/live bacteria are labeled green by SYTO 9 and dead bacteria are labeled red by PI (scale bar: 25 μm).

Figure 6

Antibacterial rates of the SEF(0.75) cryogel against (a) S. aureus and (b) E. coli under NIR irradiation (808 nm, 0.5 W/cm², 10 min) for 3 cycles.

Figure 7

(a) Cell viability of L929 cells incubated with cryogels for 24 h. (b) Optical density values of different concentrations of cryogels incubated with L929 cells for 1 day and 3 days, respectively.

Figure 8

(a) Images of hemostasis by using the gauze, SF cryogel, and SEF(0.75) cryogel. (b) Blood loss and (c) hemostatic time on the truncated rat-tail model by using the gauze, SF cryogel, and SEF(0.75) cryogel. (d) SEM images of the blood red cell adhesion on the gauze, SF cryogel, and SEF(0.75) cryogel. (e) Whole blood clotting evaluation of the gauze, SF cryogel, and SEF(0.75) cryogel.

Figure 9

Wound healing ratio of different treatments.