Protease-responsive protein hydrogel enabling spatiotemporal ClO2 release for precision treatment of intracellular infections and periodontitis
Antibiotics exhibit limited efficacy against intracellular pathogens and biofilms in periodontitis, thus often leading to drug resistance and compromised the long-term therapeutic outcomes. To address this, we developed an injectable, protease-responsive protein hydrogel (CD/BSA/GEL) for inflammatio...
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Elsevier
2025-08-01
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| Series: | Materials & Design |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0264127525007415 |
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| author | Xianxian Huang Yingjuan Zhang Yonghui Huang Qiurui Hu Zhisong Mai Yuan Qin Cui Huang Yanhua Wei Fengyuan Zhou Yicai Luo Yinge Wei Xinglu Jiang Hongbing Liao |
| author_facet | Xianxian Huang Yingjuan Zhang Yonghui Huang Qiurui Hu Zhisong Mai Yuan Qin Cui Huang Yanhua Wei Fengyuan Zhou Yicai Luo Yinge Wei Xinglu Jiang Hongbing Liao |
| author_sort | Xianxian Huang |
| collection | DOAJ |
| description | Antibiotics exhibit limited efficacy against intracellular pathogens and biofilms in periodontitis, thus often leading to drug resistance and compromised the long-term therapeutic outcomes. To address this, we developed an injectable, protease-responsive protein hydrogel (CD/BSA/GEL) for inflammation-triggered delivery of chlorine dioxide (ClO2, CD) and osteogenic proteins. The hydrogel was crosslinked via thermal polymerization of proteins and ClO2 stimulation, forming a three-dimensional network responsive to proteases in inflammatory microenvironments. Upon protease activation, the hydrogel undergoes controlled degradation, enabling sustained ClO2 release over approximately 4 days to disrupt biofilms and eradicate intracellular Porphyromonas gingivalis (P. gingivalis), while simultaneously releasing bone-regenerative protein components to promote osteogenesis. In vitro, the hydrogel demonstrated potent antibacterial activity against planktonic bacteria, intracellular pathogens, and mature biofilms. It also exhibited excellent biocompatibility, regenerative capacity, osteogenic potential, and differentiation-promoting effects to MC3T3-E1 cells. In a rat periodontitis model, the hydrogel achieved dual anti-inflammatory and osteogenic effects: ClO2 reduced expression levels of IL-10 and TNF-α, while sustained protein release enhanced alveolar bone regeneration. This protease-responsive, “on-demand” release system achieves spatiotemporal precision in antibacterial efficacy and tissue regeneration through adaptive degradation kinetics. The synergistic integration of antibacterial and regenerative functions establishes the CD/BSA/GEL hydrogel as a breakthrough platform for precision-guided periodontal therapy. |
| format | Article |
| id | doaj-art-75296f8172d4431b8d32280f1daefe25 |
| institution | DOAJ |
| issn | 0264-1275 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials & Design |
| spelling | doaj-art-75296f8172d4431b8d32280f1daefe252025-08-20T02:43:50ZengElsevierMaterials & Design0264-12752025-08-0125611432110.1016/j.matdes.2025.114321Protease-responsive protein hydrogel enabling spatiotemporal ClO2 release for precision treatment of intracellular infections and periodontitisXianxian Huang0Yingjuan Zhang1Yonghui Huang2Qiurui Hu3Zhisong Mai4Yuan Qin5Cui Huang6Yanhua Wei7Fengyuan Zhou8Yicai Luo9Yinge Wei10Xinglu Jiang11Hongbing Liao12Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi, China; Prosthodontics Department, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi, ChinaGuangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi, China; Prosthodontics Department, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi, ChinaGuangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi, China; Prosthodontics Department, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi, ChinaGuangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi, China; Prosthodontics Department, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi, ChinaGuangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi, China; Prosthodontics Department, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi, ChinaGuangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi, China; Prosthodontics Department, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi, ChinaGuangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi, China; Prosthodontics Department, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi, ChinaGuangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi, China; Prosthodontics Department, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi, ChinaGuangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi, China; Clinical Laboratory Medicine Department, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi, ChinaGuangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi, China; Prosthodontics Department, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi, ChinaGuangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi, China; Prosthodontics Department, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi, ChinaGuangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi, China; Clinical Laboratory Medicine Department, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi, China; Corresponding authors.Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi, China; Prosthodontics Department, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi, China; Corresponding authors.Antibiotics exhibit limited efficacy against intracellular pathogens and biofilms in periodontitis, thus often leading to drug resistance and compromised the long-term therapeutic outcomes. To address this, we developed an injectable, protease-responsive protein hydrogel (CD/BSA/GEL) for inflammation-triggered delivery of chlorine dioxide (ClO2, CD) and osteogenic proteins. The hydrogel was crosslinked via thermal polymerization of proteins and ClO2 stimulation, forming a three-dimensional network responsive to proteases in inflammatory microenvironments. Upon protease activation, the hydrogel undergoes controlled degradation, enabling sustained ClO2 release over approximately 4 days to disrupt biofilms and eradicate intracellular Porphyromonas gingivalis (P. gingivalis), while simultaneously releasing bone-regenerative protein components to promote osteogenesis. In vitro, the hydrogel demonstrated potent antibacterial activity against planktonic bacteria, intracellular pathogens, and mature biofilms. It also exhibited excellent biocompatibility, regenerative capacity, osteogenic potential, and differentiation-promoting effects to MC3T3-E1 cells. In a rat periodontitis model, the hydrogel achieved dual anti-inflammatory and osteogenic effects: ClO2 reduced expression levels of IL-10 and TNF-α, while sustained protein release enhanced alveolar bone regeneration. This protease-responsive, “on-demand” release system achieves spatiotemporal precision in antibacterial efficacy and tissue regeneration through adaptive degradation kinetics. The synergistic integration of antibacterial and regenerative functions establishes the CD/BSA/GEL hydrogel as a breakthrough platform for precision-guided periodontal therapy.http://www.sciencedirect.com/science/article/pii/S0264127525007415PeriodontitisIntracellular antimicrobialGelatinProtein hydrogelChlorine dioxideProtease-responsive |
| spellingShingle | Xianxian Huang Yingjuan Zhang Yonghui Huang Qiurui Hu Zhisong Mai Yuan Qin Cui Huang Yanhua Wei Fengyuan Zhou Yicai Luo Yinge Wei Xinglu Jiang Hongbing Liao Protease-responsive protein hydrogel enabling spatiotemporal ClO2 release for precision treatment of intracellular infections and periodontitis Materials & Design Periodontitis Intracellular antimicrobial Gelatin Protein hydrogel Chlorine dioxide Protease-responsive |
| title | Protease-responsive protein hydrogel enabling spatiotemporal ClO2 release for precision treatment of intracellular infections and periodontitis |
| title_full | Protease-responsive protein hydrogel enabling spatiotemporal ClO2 release for precision treatment of intracellular infections and periodontitis |
| title_fullStr | Protease-responsive protein hydrogel enabling spatiotemporal ClO2 release for precision treatment of intracellular infections and periodontitis |
| title_full_unstemmed | Protease-responsive protein hydrogel enabling spatiotemporal ClO2 release for precision treatment of intracellular infections and periodontitis |
| title_short | Protease-responsive protein hydrogel enabling spatiotemporal ClO2 release for precision treatment of intracellular infections and periodontitis |
| title_sort | protease responsive protein hydrogel enabling spatiotemporal clo2 release for precision treatment of intracellular infections and periodontitis |
| topic | Periodontitis Intracellular antimicrobial Gelatin Protein hydrogel Chlorine dioxide Protease-responsive |
| url | http://www.sciencedirect.com/science/article/pii/S0264127525007415 |
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