Regulatory T cells engineered with polyphenol-functionalized immunosuppressant nanocomplexes for rebuilding periodontal hard tissue under inflammation-challenged microenvironment

Bo Zhang; Guidong Gong; Yunxiang He; Jialing Liu; Bo Wang; Yifei Li; Jie Fang; Zhihe Zhao; Junling Guo

doi:10.1016/j.biomaterials.2024.122961

Regulatory T cells engineered with polyphenol-functionalized immunosuppressant nanocomplexes for rebuilding periodontal hard tissue under inflammation-challenged microenvironment

Biomaterials. 2024 Nov 9:315:122961. doi: 10.1016/j.biomaterials.2024.122961. Online ahead of print.

Authors

Bo Zhang¹, Guidong Gong², Yunxiang He³, Jialing Liu¹, Bo Wang⁴, Yifei Li⁵, Jie Fang⁶, Zhihe Zhao⁷, Junling Guo⁸

Affiliations

¹ State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, China.
² BMI Center for Biomass Materials and Nanointerfaces, College of Biomass Science and Engineering, Sichuan University, Chengdu, Sichuan, 610065, China; National Engineering Laboratory for Clean Technology of Leather Manufacture, Sichuan University, Chengdu, Sichuan, 610065, China.
³ BMI Center for Biomass Materials and Nanointerfaces, College of Biomass Science and Engineering, Sichuan University, Chengdu, Sichuan, 610065, China; National Engineering Laboratory for Clean Technology of Leather Manufacture, Sichuan University, Chengdu, Sichuan, 610065, China; Key Laboratory of Leather Chemistry and Engineering, Sichuan University, Ministry of Education, Chengdu, 610065, China.
⁴ CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
⁵ Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education (MOE), Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
⁶ State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, China. Electronic address: [email protected].
⁷ State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, China. Electronic address: [email protected].
⁸ BMI Center for Biomass Materials and Nanointerfaces, College of Biomass Science and Engineering, Sichuan University, Chengdu, Sichuan, 610065, China; National Engineering Laboratory for Clean Technology of Leather Manufacture, Sichuan University, Chengdu, Sichuan, 610065, China; Key Laboratory of Leather Chemistry and Engineering, Sichuan University, Ministry of Education, Chengdu, 610065, China; State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu, Sichuan, 610065, China; Bioproducts Institute, Department of Chemical and Biological Engineering, The University of British Columbia, Vancouver, BC, V6T 1Z4, Canada. Electronic address: [email protected].

PMID: 39549440
DOI: 10.1016/j.biomaterials.2024.122961

Abstract

Global aging heightens the risk of oral disorders, among which periodontitis is the major cause of tooth loss in the aging population. The regeneration of damaged periodontal hard tissue is highly challenging due to the existence of the refractory local inflammation. Owing to the potent anti-inflammatory capabilities, regulatory T cells hold great promise in immunotherapies for tissue regeneration. However, the transferred regulatory T cells can alter their phenotypes and functions in local inflammatory milieu, significantly impairing their therapeutic efficacy. Herein, we introduce a novel regulatory T cell-based nanobiohybrid system bearing polyphenol-functionalized rapamycin nanocomplexes. The sustained in situ release of immunosuppressant rapamycin from the cell-attached nanocomplexes maintains the anti-inflammatory phenotype of regulatory T cells in the inflammatory milieu. The synergistic actions of the anti-inflammatory cytokines secreted and the immunosuppressant released guide a pro-resolving polarization of macrophages and enhance osteogenic differentiation of bone marrow-derived stromal cells. The stabilized phenotype of the regulatory T cells dramatically promoted the resolution of periodontal inflammation and the repair of the hard tissue (alveolar bone) in vivo. Overall, these studies highlight a potent regulatory T cell-based nanobiohybrid therapy to treat periodontitis by modulating periodontal immune microenvironment.

Keywords: Cell-based therapy; Immunomodulation; Periodontal hard tissue; Regulatory T cells; metal‐phenolic networks.