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Injectable Dual-Cross-Linked Hydrogels Enabling Sequential Drug Release for Synergistic Periodontitis Therapy.

Chang-Hai Zhou1, Yi Gao2, Xing-Long Zhou1

  • 1School of Chemical Engineering, Sichuan University, Chengdu 610065, China.

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|March 30, 2026
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Summary
This summary is machine-generated.

This study introduces an injectable hydrogel for periodontitis treatment. It sequentially releases antimicrobial and anti-inflammatory drugs to effectively manage infection and inflammation, promoting tissue regeneration.

Keywords:
anti-inflammatory drugantibacterial druginjectable hydrogelsperiodontitissequential drug releasesustained-release preparations

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Area of Science:

  • Biomaterials Science
  • Periodontology
  • Drug Delivery Systems

Background:

  • Periodontitis is a chronic infectious disease driven by bacteria and host immune response.
  • Effective periodontitis treatment requires combined antimicrobial and anti-inflammatory strategies.
  • Localized antimicrobial environments are crucial for anti-inflammatory drug efficacy in periodontitis therapy.

Purpose of the Study:

  • To develop a double-cross-linked injectable hydrogel for codelivery of antimicrobial and anti-inflammatory drugs.
  • To achieve sequential drug release for synergistic periodontitis treatment.
  • To create a system that adapts to periodontal pockets and resists salivary flow.

Main Methods:

  • Development of a temperature-responsive, dynamically cross-linked injectable hydrogel.
  • Codelivery carrier for metronidazole (antimicrobial) and metformin (anti-inflammatory).
  • In vitro assessment of sequential drug release profiles and in vivo validation in a rat periodontitis model.

Main Results:

  • The hydrogel demonstrated sustained release of metronidazole for 7 days and metformin over 14 days.
  • The system adapted to irregular geometries and self-reinforced, resisting salivary flow.
  • Synergistic antibacterial, anti-inflammatory, and regenerative effects were confirmed in vivo.

Conclusions:

  • The developed hydrogel system enables localized, sequential drug release for enhanced periodontitis therapy.
  • This injectable and self-reinforcing hydrogel shows significant potential for clinical periodontitis management.
  • The sequential release strategy optimizes drug efficacy by establishing an antimicrobial environment before anti-inflammatory action.