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TiO2 NPs improve ultrasound response: CS/β‑GP/TiO2 NP hydrogel enabling on‑demand administration

  • Authors:
    • Yue Zhou
    • Yi-Ran Yao
    • Yan Xu
    • Xin Rong
    • Yue-Feng Qiu
    • Ting-Yue Qi
  • View Affiliations / Copyright

    Affiliations: Department of Ultrasound, Medical Imaging Center, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu 225012, P.R. China, Department of Ultrasound, Medical Imaging Center, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu 225012, P.R. China, College of Chemical Engineering, Nanjing Tech University, Nanjing, Jiangsu 211816, P.R. China
    Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 142
    |
    Published online on: June 17, 2025
       https://doi.org/10.3892/br.2025.2020
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Abstract

The present study developed a novel injectable, biocompatible, and thermosensitive hydrogel system for ultrasound‑triggered drug release, using a chitosan/sodium β‑glycerophosphate/titanium dioxide nanoparticle (CS/β‑GP/TiO2 NP) composite. The inclusion of TiO2 NPs aimed to enhance ultrasound sensitivity, enabling precise therapeutic release to targeted tissues. The hydrogels displayed excellent injectability (maximum injection force <6.5 N) and gelled effectively at body temperature. Biocompatibility was confirmed through Cell Counting Kit‑8, LIVE/DEAD, and western blot assays. The present study demonstrated that hydrogels with TiO2 NPs significantly increased the release rates of sodium fluorescein and bovine serum albumin, affirming the role of TiO2 NPs as a sensitizer. This establishes the CS/β‑GP/TiO2 NP hydrogel as a promising system for ultrasound‑responsive drug delivery. Potential applications include drug delivery, tissue engineering, and wound healing, with the system offering controlled and targeted therapy under ultrasound stimulation. Future research will optimize hydrogel properties, assess in vivo performance, and evaluate long‑term stability and effectiveness in clinical settings.
View Figures

Figure 1

Fourier transform infrared
spectroscopy for thermally responsive hydrogels, showing the
incorporation of TiO2 NPs into the CS/β-GP co-polymer.
TiO2 NPs, titanium dioxide nanoparticles; CS/β-GP,
chitosan/β-glycerophosphate.

Figure 2

Storage modulus as a function of
TiO2 NP concentration from 20 to 50˚C indicating the low
critical solution temperature transition points from liquid to
solid state. TiO2 NPs, titanium dioxide nanoparticles;
CS/β-GP, chitosan/β-glycerophosphate.

Figure 3

Injectability of the pure CS/β-GP
hydrogel and thermally responsive hydrogels containing 0.5, 1.0 and
1.5% wt./vol. TiO2 NPs. No significant difference was
observed between groups. The forces recorded for all hydrogels were
below the maximum force that can be comfortably applied to a
syringe by a surgeon's hand, highlighted on the graph at 22.6 N.
TiO2 NPs, titanium dioxide nanoparticles; CS/β-GP,
chitosan/β-glycerophosphate.

Figure 4

CCK-8 assays of different composite
hydrogels. Different composite hydrogels were not significantly
different from the control group by CCK-8 assay. There were no
statistically significant differences (P>0.05). CCK-8, Cell
Counting Kit-8; OD, optical density; CS/β-GP,
chitosan/β-glycerophosphate; TiO2 NPs, titanium dioxide
nanoparticles.

Figure 5

Survival rates of different composite
hydrogels. The survival rates of cells co-cultured with various
hydrogel formulations were not significantly different from the
those of the control group, as assessed by LIVE/DEAD assay.
CS/β-GP, chitosan/β-glycerophosphate; TiO2 NPs, titanium
dioxide nanoparticles.

Figure 6

Western blotting results of different
composite hydrogels. The results of western blotting assay revealed
no significant differences in cell protein expression among the
different groups (P>0.05). PCNA, proliferating cell nuclear
antigen; CS/β-GP, chitosan/β-glycerophosphate; TiO2 NPs,
titanium dioxide nanoparticles.

Figure 7

Cumulative release of NaF from
NaF-loaded thermally responsive hydrogels. (A) Diffusion-related
release of NaF from the pure CS/β-GP and CS/β-GP + 1.5%
TiO2 NP groups up to 24 h. (B) Ultrasound triggered
release of NaF following the first ultrasound treatment.
***P<0.001. NaF, sodium fluorescein; CS/β-GP,
chitosan/β-glycerophosphate; TiO2 NPs, titanium dioxide
nanoparticles.

Figure 8

Cumulative release of BSA from BSA
loaded thermally responsive hydrogels. (A) Diffusion related
release of pure CS/β-GP and CS/β-GP + 1.5% TiO2 NP
groups up to 72 h. Ultrasound-triggered release of BSA is shown
following (B) first ultrasound treatment, (C) second ultrasound
treatment and (D) third ultrasound treatment.
***P<0.001 and ****P<0.0001. BSA,
bovine serum albumin; CS/β-GP, chitosan/β-glycerophosphate;
TiO2 NPs, titanium dioxide nanoparticles.
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Copy and paste a formatted citation
Spandidos Publications style
Zhou Y, Yao Y, Xu Y, Rong X, Qiu Y and Qi T: TiO<sub>2</sub> NPs improve ultrasound response: CS/&beta;‑GP/TiO<sub>2</sub> NP hydrogel enabling on‑demand administration. Biomed Rep 23: 142, 2025.
APA
Zhou, Y., Yao, Y., Xu, Y., Rong, X., Qiu, Y., & Qi, T. (2025). TiO<sub>2</sub> NPs improve ultrasound response: CS/&beta;‑GP/TiO<sub>2</sub> NP hydrogel enabling on‑demand administration. Biomedical Reports, 23, 142. https://doi.org/10.3892/br.2025.2020
MLA
Zhou, Y., Yao, Y., Xu, Y., Rong, X., Qiu, Y., Qi, T."TiO<sub>2</sub> NPs improve ultrasound response: CS/&beta;‑GP/TiO<sub>2</sub> NP hydrogel enabling on‑demand administration". Biomedical Reports 23.3 (2025): 142.
Chicago
Zhou, Y., Yao, Y., Xu, Y., Rong, X., Qiu, Y., Qi, T."TiO<sub>2</sub> NPs improve ultrasound response: CS/&beta;‑GP/TiO<sub>2</sub> NP hydrogel enabling on‑demand administration". Biomedical Reports 23, no. 3 (2025): 142. https://doi.org/10.3892/br.2025.2020
Copy and paste a formatted citation
x
Spandidos Publications style
Zhou Y, Yao Y, Xu Y, Rong X, Qiu Y and Qi T: TiO<sub>2</sub> NPs improve ultrasound response: CS/&beta;‑GP/TiO<sub>2</sub> NP hydrogel enabling on‑demand administration. Biomed Rep 23: 142, 2025.
APA
Zhou, Y., Yao, Y., Xu, Y., Rong, X., Qiu, Y., & Qi, T. (2025). TiO<sub>2</sub> NPs improve ultrasound response: CS/&beta;‑GP/TiO<sub>2</sub> NP hydrogel enabling on‑demand administration. Biomedical Reports, 23, 142. https://doi.org/10.3892/br.2025.2020
MLA
Zhou, Y., Yao, Y., Xu, Y., Rong, X., Qiu, Y., Qi, T."TiO<sub>2</sub> NPs improve ultrasound response: CS/&beta;‑GP/TiO<sub>2</sub> NP hydrogel enabling on‑demand administration". Biomedical Reports 23.3 (2025): 142.
Chicago
Zhou, Y., Yao, Y., Xu, Y., Rong, X., Qiu, Y., Qi, T."TiO<sub>2</sub> NPs improve ultrasound response: CS/&beta;‑GP/TiO<sub>2</sub> NP hydrogel enabling on‑demand administration". Biomedical Reports 23, no. 3 (2025): 142. https://doi.org/10.3892/br.2025.2020
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