A five-in-one novel MOF-modified injectable hydrogel with thermo-sensitive and adhesive properties for promoting alveolar bone repair in periodontitis: Antibacterial, hemostasis, immune reprogramming, pro-osteo-/angiogenesis and recruitment

Shiyuan Yang; Yan Zhu; Chunxiao Ji; Huimin Zhu; An Lao; Ran Zhao; Yue Hu; Yuning Zhou; Jia Zhou; Kaili Lin; Yuanjin Xu

doi:10.1016/j.bioactmat.2024.07.016

A five-in-one novel MOF-modified injectable hydrogel with thermo-sensitive and adhesive properties for promoting alveolar bone repair in periodontitis: Antibacterial, hemostasis, immune reprogramming, pro-osteo-/angiogenesis and recruitment

Bioact Mater. 2024 Jul 24:41:239-256. doi: 10.1016/j.bioactmat.2024.07.016. eCollection 2024 Nov.

Authors

Shiyuan Yang^{1

2}, Yan Zhu^{1

2}, Chunxiao Ji^{2

3}, Huimin Zhu^{1

2}, An Lao^{2

3}, Ran Zhao^{2

4}, Yue Hu^{1

2}, Yuning Zhou^{1

2}, Jia Zhou^{1

2}, Kaili Lin^{2

3}, Yuanjin Xu^{1

2}

Affiliations

¹ Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China.
³ Department of Oral and Cranio-maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁴ Department of Oral Mucosal Diseases, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

Periodontitis is a chronic inflammatory disease caused by plaque that destroys the alveolar bone tissues, resulting in tooth loss. Poor eradication of pathogenic microorganisms, persistent malignant inflammation and impaired osteo-/angiogenesis are currently the primary challenges to control disease progression and rebuild damaged alveolar bone. However, existing treatments for periodontitis fail to comprehensively address these issues. Herein, an injectable composite hydrogel (SFD/CS/ZIF-8@QCT) encapsulating quercetin-modified zeolitic imidazolate framework-8 (ZIF-8@QCT) is developed. This hydrogel possesses thermo-sensitive and adhesive properties, which can provide excellent flowability and post-injection stability, resist oral fluid washout as well as achieve effective tissue adhesion. Inspirationally, it is observed that SFD/CS/ZIF-8@QCT exhibits a rapid localized hemostatic effect following implantation, and then by virtue of the sustained release of zinc ions and quercetin exerts excellent collective functions including antibacterial, immunomodulation, pro-osteo-/angiogenesis and pro-recruitment, ultimately facilitating excellent alveolar bone regeneration. Notably, our study also demonstrates that the inhibition of osteo-/angiogenesis of PDLSCs under the periodontitis is due to the strong inhibition of energy metabolism as well as the powerful activation of oxidative stress and autophagy, whereas the synergistic effects of quercetin and zinc ions released by SFD/CS/ZIF-8@QCT are effective in reversing these biological processes. Overall, our study presents innovative insights into the advancement of biomaterials to regenerate alveolar bone in periodontitis.

Keywords: Alveolar bone regeneration; Hydrogel; Periodontitis; Quercetin; ZIF-8.