Local periodontal injection, systemic heart repair: A dual-functional hydrogel for non-invasive concurrent treatment of periodontitis and myocardial infarction

  • Bioact Mater. 2026 Mar 4:62:17-33. doi: 10.1016/j.bioactmat.2026.02.049.
Qinfeng Ding  1  2 ,  Yilong Teng  3 ,  Hong Zhu  4 ,  Zhitong Jia  3 ,  Shuo Xu  1  2 ,  Bin Hu  3 ,  Boyan Chen  1  2  4 ,  Jiewen Dai  1  5 ,  Jian Sun  1 ,  Ping Nie  1 ,  Zhixiang Liu  6 ,  Qijing Chen  3 ,  Xudong Wang  1 ,  Xiaoyang Xu  6 ,  Xueqing Zhang  3 ,  Shengzhong Duan  4  7
Affiliations
  • 1. Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, 200011, China.
  • 2. Laboratory of Oral Microbiota and Systemic Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
  • 3. Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmaceutical Sciences, and National Key Laboratory of Innovative Immunotherapy, Shanghai Jiao Tong University, Shanghai, 200240, China.
  • 4. Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, 166 North Qiutao Rd, Hangzhou, 310000, China.
  • 5. Foshan Stomatological Hospital & School of Medicine, Foshan University, Foshan, Guangdong, 528000, China.
  • 6. Department of Chemical and Materials Engineering, and Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, USA.
  • 7. State Key Laboratory of Transvascular Implantation Devices, Hangzhou, Zhejiang, 310000, China.
PMID: 41810018 DOI: 10.1016/j.bioactmat.2026.02.049
Abstract

Periodontitis and myocardial infarction (MI), the leading cause of mortality worldwide, represent globally prevalent inflammatory diseases with bidirectional pathophysiological links. Despite the urgent demand for non-invasive strategies capable of alleviating local periodontal destruction while mitigating associated systemic cardiovascular complications, no integrated treatment modality currently exists. To address this challenge, a protein-loaded Antibacterial hydrogel, thiolated chitosan/AMP-PEG-maleimide (C1.5P4/BMP-2), with novel sustained protein release properties was developed. This hydrogel features an interconnected microporous architecture that: (1) enables high-efficiency BMP-2 protein encapsulation, (2) preserves protein bioactivity while ensuring sustained release, thereby addressing the recognized challenge of hydrogel-based protein delivery, (3) confers potent Antibacterial properties, (4) facilitates remote cardiac function improvement by resolving periodontal inflammation. In murine models, locally, it attenuated alveolar bone loss (2-fold greater bone regeneration vs controls) while systemically improving post-MI cardiac function (75.6% higher ejection fraction). Mechanistically, the hydrogel's protein-protective microenvironment synergized with its antimicrobial action selectively inhibiting Gram-negative (G-) anaerobic pathogens (primary periodontal culprits) while enriching Gram-positive (G+) commensals, regulating biofilm G-/G+ ratio. Concomitantly, this dual action modulates the oral-cardiac inflammatory axis, specifically downregulating B2 cell/TNF-α signaling to mitigate systemic inflammation associated with MI. Collectively, this study presents a novel non-invasive protein-stabilizing hydrogel that addresses periodontitis-MI comorbidity through sustained osteogenic factor delivery coupled with microbiome-immune modulation.

Keywords
B2 cell; Microbial dysbiosis; Multifunctional hydrogel; Myocardial infarction; Periodontitis.
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