Bioactive Carboxymethyl Starch-Based Hydrogels Decorated with CuO Nanoparticles: Antioxidant and Antimicrobial Properties and Accelerated Wound Healing In Vivo - PubMed
- ️Fri Jan 01 2021
Bioactive Carboxymethyl Starch-Based Hydrogels Decorated with CuO Nanoparticles: Antioxidant and Antimicrobial Properties and Accelerated Wound Healing In Vivo
Zahra Abdollahi et al. Int J Mol Sci. 2021.
Abstract
In this study, nanocomposite hydrogels composed of sodium carboxymethylated starch (CMS)-containing CuO nanoparticles (CMS@CuO) were synthesized and used as experimental wound healing materials. The hydrogels were fabricated by a solution-casting technique using citric acid as a crosslinking agent. They were characterized by Fourier-transform infrared spectroscopy (FTIR), energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), and thermogravimetric analysis (TGA) to evaluate their physicochemical properties. In addition, swelling, antibacterial activities, antioxidant activities, cytotoxicity, and in vivo wound healing were investigated to evaluate the wound healing potential of the CMS@CuO nanocomposite hydrogels. Growth inhibition of the Gram-positive and Gram-negative pathogens, antioxidant activity, and swelling were observed in the CMS@CuO nanocomposite hydrogels containing 2 wt.% and 4 wt.% CuO nanoparticles. The hydrogel containing 2 wt.% CuO nanoparticles displayed low toxicity to human fibroblasts and exhibited good biocompatibility. Wounds created in rats and treated with the CMS@2%CuO nanocomposite hydrogel healed within 13 days, whereas wounds were still present when treated for the same time-period with CMS only. The impact of antibacterial and antioxidant activities on accelerating wound healing could be ascribed to the antibacterial and antioxidant activities of the nanocomposite hydrogel. Incorporation of CuO nanoparticles in the hydrogel improved its antibacterial properties, antioxidant activity, and degree of swelling. The present nanocomposite hydrogel has the potential to be used clinically as a novel wound healing material.
Keywords: CuO nanoparticles; antibacterial; antioxidant; hydrogel nanocomposites; sodium carboxymethyl starch; wound healing.
Conflict of interest statement
The authors declare no conflict of interest.
Figures
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Schematic of the application of bioactive carboxymethylated starch (CMS)-containing CuO nanoparticles (CMS@CuO) nanocomposite hydrogel in wound healing. ROS: reactive oxygen species.
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Fourier transform infrared (FTIR) (a), X-ray diffraction (XRD) (b), and thermogravimetric analysis (TGA) (c) of CMS, CuO nanoparticles, and the CMS@2%CuO nanocomposite hydrogel.

Field emission scanning electron microscopy (FESEM) images (a) and energy-dispersive X-ray spectroscopy (EDS) spectra and tabulated data (b) of CMS, CuO nanoparticles, and the CMS@2%CuO nanocomposite hydrogel. CMS: carboxymethylated starch; NPs: nanoparticles.

Histograms and photographs depicting the swelling behavior of the CMS hydrogel and the CMS@CuO nanocomposite hydrogels containing 2 wt.% and 4 wt.% CuO nanoparticles. The histogram on the left shows swelling in the presence of different concentrations of citric acid as crosslinking agent (a). The histogram on the right and the photograph above show the antioxidant activity of CMS, CuO nanoparticles and the CMS@CuO nanocomposite hydrogels with 2 wt.% and 4 wt.% CuO nanoparticles (b).

Antibacterial activity of CMS, CuO nanoparticles, the CMS@2%CuO nanocomposite hydrogel, and the CMS@4%CuO nanocomposite hydrogel against different Gram-positive and Gram-negative bacteria. (a) cell cultures (b) charts. For each chart, columns marked with asterisks (*) denote significant difference compared with pure CMS (p < 0.05).

Cell viability (%) of human fibroblasts after exposure to CMS, CMS@2%CuO, and CMS@4%CuO specimens in the culture medium for 24 h (a), 48 h (b), and 72 h (c). Asterisks (*) indicate a significant difference (p < 0.05) between viability percent of treated cells with CMS@2%CuO as most efficient hydrogel and ones treated with CMS and CMS@4%CuO in one-way ANOVA test at a confidence interval of 95%.

Macroscopic photographs of the wounds treated with the control, CMS, and the CMS@2%CuO nanocomposite hydrogel specimens at different time periods (a,b) and histograms of the percentage of wound healing (c) and wound length (d). For each chart, columns labeled with an asterisk (*,**) are significantly different from the control (p < 0.05 and p < 0.01).

Schematic of the application of a nanocomposite hydrogel with antibacterial and antioxidant properties to promote wound healing.

Schematic of the preparation of (a) sodium carboxymethyl starch (CMS) and (b) nanocomposite hydrogels that consists of CuO nanoparticles (NPs) dispersed within the citric acid crosslinked CMS polymer matrix.
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