In Situ Self-Cross-Linkable, Long-Term Stable Hyaluronic Acid Filler by Gallol Autoxidation for Tissue Augmentation and Wrinkle Correction

Jung Seung Lee, Jung Ho Cho, Soohwan An, Jisoo Shin, Soojeong Choi, Eun Je Jeon, Seung Woo Cho

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


Injectable fillers mainly aim to augment tissue volume and correct wrinkles in cosmetic and plastic reconstructions. However, the development of long-lasting, injectable fillers with minimal complications of pain, toxicity, and displacement has been challenging because of the absence of reliable cross-linking chemistry. Here, we report a novel cross-linker-free injectable hydrogel formulated by autoxidation as a highly biocompatible, easily injectable, and long-term volumetrically stable filler agent. Self-cross-linkable hyaluronic acid (SC-HA) with gallol moieties could form a hydrogel via autoxidation of gallols in vivo without additional cross-linking agents. The gelation of SC-HA in situ after injection is accelerated by the self-production of oxygen species and endogenous peroxidase in vivo. The SC-HA filler does not require a high injection force, thus minimizing pain, bleeding, and tissue damage-associated complications. In addition, improved tissue adhesiveness of the SC-HA hydrogel by oxidized gallols (shear strength; 2 kPa) prevented displacement of the filler constructs from the injection site. The SC-HA filler retained its mechanical properties in vivo (600-700 Pa) for wrinkle correction and volumetric augmentation up to 1 year after injection. Overall, the performance of the SC-HA hydrogel as an injectable dermal filler was superior to that of commercially available, chemically cross-linked biphasic HA filler composites in terms of injectability, tissue adhesiveness, and long-term volumetric augmentation. Our injectable HA hydrogel with no need of cross-linkers provides a long-lasting filler that has clinical utility for cosmetic applications.

Original languageEnglish
Pages (from-to)9614-9624
Number of pages11
JournalChemistry of Materials
Issue number23
Publication statusPublished - 2019 Dec 10

Bibliographical note

Funding Information:
The protocol for animal experiments was reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) of the Yonsei Laboratory Animal Research Center (YLARC) (protocol number: IACUC-201802-700-01). This work was supported by grants (2017R1A2B3005994 and 2018M3A9H1021382) from the National Research Foundation (NRF) of Korea funded by the Ministry of Science and ICT (MSIT), Republic of Korea. This work was also supported by the Institute for Basic Science (IBS-R026-D1).

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Chemical Engineering(all)
  • Materials Chemistry

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