A dual-cross-linked hydrogel based on hyaluronic acid/gelatin tethered via tannic acid: mechanical properties’ enhancement and stability control


Extracellular matrix (ECM) as a network is mainly composed of glycosaminoglycans and proteins. Among these glycosaminoglycans and proteins that naturally occur in ECM, hyaluronic acid (HA) and gelatin attract more attentions. In this work, a chemically cross-linked HA/gelatin hydrogel (HG hydrogel) was firstly fabricated, and then, tannic acid (TA) was introduced as a physical cross-linker, to form a dual-cross-linked network (HG-TAx hydrogels). The strong hydrogen bonding between TA and HG hydrogel resulted in lower swelling ratio, decreasing from 220% (pristine HG hydrogels) to 7.5% (HG-TA25 hydrogels) and stronger mechanical properties increasing from 6 kPa (HG hydrogel) to 160 kPa (HG-TA25 hydrogel). The hydrogel stability in enzyme was significantly improved, attributing to the hyaluronidase inhibition activity of TA. The degradation time significantly increased along with the addition of TA (from 7 up to 21 days). Furthermore, the HG-TAx hydrogels exhibited good cleavage ability to reactive oxygen species (ROS) that could be generated in human tissues, and the antioxidant capacity increased up to 24.2 mg/mL of L-ascorbic acid standard. The improved mechanical properties, prolonged degradation time, and potential antioxidant ability of the HG-TAx hydrogels could pave the way for the design of biomaterials. Furthermore, TA has shown potential biological functions properties and brought the great potential of the HG-TAx hydrogels for implant applications.

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Data availability statement

The raw/processed data required to reproduce these findings cannot be shared at this time as the data also form part of an ongoing study. However, they can be provided upon requested.


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This research was financially supported by the Special Fund Project for Guangdong Academy of Sciences to Build First-Class Research Institutions in China (2020GDASYL-20200103039, 2019GDASYL-0105009, 2019GDASYL-0501003, 2019GDASYL-0105008, 2019GDASYL-0402002, and 2017GDASCX-0103), Guangdong Basic and Applied Basic Research Foundation (2019A1515110207), Science and Technology Program of Guangzhou (202002030381), and Science and Technology Planning Project of Guangdong Province of China (2017A070701019).

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SY conceptualization, methodology, analysis, and writing original draft and reviewing. YJ preparing samples and characterization, and reviewing and editing biological part. CG editing. DL material characterization. ZG material characterization. DP reviewing and editing. QL validation and reviewing.

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Correspondence to Shan Yu or Qunfeng Liu.

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The authors declared that they have no conflicts of interest to this work. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted.

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Yu, S., Ji, Y., Guo, C. et al. A dual-cross-linked hydrogel based on hyaluronic acid/gelatin tethered via tannic acid: mechanical properties’ enhancement and stability control. Iran Polym J 30, 307–317 (2021). https://doi.org/10.1007/s13726-020-00891-9

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  • Hyaluronic acid
  • Gelatin
  • Tannic acid
  • Dual-cross-linked hydrogel
  • Mechanical properties