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SCIENCE CHINA Materials, Volume 64 , Issue 4 : 1035-1046(2021) https://doi.org/10.1007/s40843-020-1480-3

A smart hydrogel for on-demand delivery of antibiotics and efficient eradication of biofilms

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  • ReceivedMay 26, 2020
  • AcceptedAug 7, 2020
  • PublishedOct 26, 2020

Abstract


Funded by

the National Key R&D Program of China

Synthetic Biology Research(2019YFA0904500)

the National Natural Science Foundation of China(21725402,51672191)

and the Natural Science Foundation of Shanghai(19ZR1415600)


Acknowledgment

This work was supported by the National Key R&D Program of China, Synthetic Biology Research (2019YFA0904500), the National Natural Science Foundation of China (21725402 and 51672191), and the Natural Science Foundation of Shanghai (19ZR1415600). The authors acknowledge the ECNU Multifunctional Platform for Innovation (011) for the animal experiments.


Interest statement

The authors declare that they have no conflict of interest.


Contributions statement

Hu J prepared and evaluated the in vitro antibacterial properties of the hydrogels; Hu J, Zhang C, Zhou L and Kong Y performed the in vivo experiments; Hu Q contributed to the physicochemical characterization of the hydrogel; Song D, Zhang Y and Cheng Y designed and supervised the study and wrote the manuscript. All the authors contributed to the general discussion.


Author information

Jingjing Hu is an associate professor of biomaterials at the School of Life Science, East China Normal University. She received her PhD degree from the University of Science and Technology of China. Her research interests mainly focus on the design of antibacterial materials and smart hydrogels.


Dianwen Song is a full professor and chief physician at the Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University. He received his MD and PhD degrees from the Second Military Medical University. His research interests focus on the development of tissue-engineered bone and mechanism of bone metastasis in malignancies.


Yiyun Cheng is a full professor of biomedical engineering at the School of Life Sciences, East China Normal University. He received his PhD degree from the University of Science and Technology of China and was a postdoctoral fellow at Washington University in St. Louis, MO. His research interests focus on the rational design of polymers for the delivery of biomacromolecules.


Yadong Zhang is a chief physician and professor at the Department of Orthopaedics, Fengxian Hospital affiliated to Southern Medical University. He received his PhD from Shanghai Jiao Tong University. He is expert in the treatment of spinal diseases. His research interests focus on the design of smart hydrogels and nanomedicines for bone repair and the treatment of bacterial infection.


Supplement

Supplementary information

Supporting data are available in the online version of the paper.


References

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  • Figure 1

    A smart hydrogel for the treatment of biofilm-associated infections. (a) Preparation of the hydrogel by mixing oxidized dextran, amino-glycosides and Pec together via the formation of Schiff base linkages. (b) Illustration of the biofilm eradication and bacteria killing by Pec and Ami released from the hydrogel. (c) Residual biomass generated by P. aeruginosa biofilm on a glass coverslip after treatment with Ami (16 µg mL−1), Pec (20 mg mL−1), and Ami/Pec mixture (16 µg mL−1 for Ami, and 20 mg mL−1 for Pec), respectively. (d) Crystal violet staining of the coverslips in (c). (e) Counts of live P. aeruginosa in the treated P. aeruginosa biofilms in (c). *P < 0.05, **P< 0.01 analyzed by student’s t-test.

  • Figure 2

    Properties of the Ami/Pec complex hydrogel. (a) Preparation of the Ami/Pec complex hydrogel. Ami gel and Pec gel with equal concentrations of oxidized dextran and Ami/Pec were prepared as controls. (b) Thixotropic property of the complex hydrogel, the angular frequency was kept constant at 10 rad s−1 with an alternative strain of 1% and 100%. (c) Shear thinning property of the complex hydrogel. The inserted image is the injection of complex gel through a syringe (1.2  mm × 30 mm). (d) Accumulative release of Ami and Pec from the Ami/Pec complex hydrogel at pH 7.4 and 5.0, respectively. (e) Viability of NIH 3T3 cells treated with the complex hydrogel at different concentrations. (f) Hemolytic activity of the complex hydrogel. Triton X-100 and PBS were tested as the positive and negative controls, respectively.

  • Figure 3

    In vitro biofilm eradiation and antibacterial activity of the complex hydrogel. (a) SEM images of the P. aeruginosa biofilm formed on a glass coverslip. Scale bar: 2 µm. (b) Confocal images of the treated P. aeruginosa biofilm by a live-dead bacteria staining. (c) Residual biomass and (d) the count of live bacteria in the biofilm after treatment. (e) Inhibition zone of the hydrogels on P. aeruginosa biofilm. *P< 0.05, **P< 0.01 analyzed by student’s t-test.

  • Figure 4

    In vivo biofilm eradiation and antibacterial activity of the complex hydrogel. (a) Illustration of catheter implantation model. (b) Residual biomass on the catheter after treatment. The inserted images on bars are the photographs of the harvested catheters stained by crystal violet. (c) Counts of live P. aeruginosa on the catheters after treatment. *P< 0.05, **P< 0.01 analyzed by student’s t-test.

  • Figure 5

    Performance of the hydrogel in the treatment of biofilm infections in vivo. (a) Illustration of biofilm infection model. (b) Survival curve of the mice during the treatment. (c) Photographs of lung and liver harvested from the treated mice. (d) Counts of live bacteria in the organs harvested from the treated mice. (e) Gram staining of the skin harvested from the infection site after treatment. The arrows indicate stained P. aeruginosa in the skin tissue sections. Scale bar: 200 µm. *P< 0.05, **P< 0.01 analyzed by student’s t-test.

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