Abstract
Osteoarthritis (OA) is a widespread joint disease, yet there are limited effective treatment strategies that preserve articular cartilage and mitigate damage to other joint elements. The role of inflammation is crucial, driving cartilage degeneration and synovitis in OA. While photothermal therapy (PTT) has shown promise in cancer and antibacterial treatments, its application in OA remains underexplored. In this study, we developed an optimized injectable hydrogel for PTT in OA, formulated by combining a hyaluronic acid (HA)-thiourea (NCSN) solution with Cu2+ (HSC hydrogel). Leveraging the dynamic and reversible chelation between NCSN and Cu2+, this hydrogel exhibits significant photothermal properties. Furthermore, the unchelated NCSN aids in neutralizing excessive reactive oxygen species. As a result, the HSC hydrogel offers easy injectability, inherent self-healing properties, and potent photothermal performance, negating the requirement for external photothermal agents. In vitro analyses confirmed the non-cytotoxic feature of HSC hydrogel to chondrocytes. When combined with near-infrared (NIR) treatment (HSC/NIR), the hydrogel effectively bolsters chondrocyte anabolism while diminishing catabolism and inflammation triggered by IL-1β. In vivo studies highlight remarkable therapeutic potential of HSC/NIR in OA, demonstrating reductions in cartilage degeneration, synovitis, osteophyte formation, and subchondral sclerosis. Transcriptomic study illuminates the mechanism by which HSC/NIR counteracts IL-1β-driven chondrocyte transcriptomic shifts, particularly inhibiting the JAK/STAT signaling pathway and promoting cell proliferation. Additionally, HSC/NIR moderates macrophage polarization, mitigating the inflammatory milieu and consequently promoting chondrocyte anabolism and curtailing catabolism and inflammation. This study emphasizes the effect and strength of hydrogel-based PPT on cartilage homeostasis, inflammatory responses, and potential immune modulation, offering a new frontier in OA treatment paradigms.
Graphical Abstract
The study developed an optimized injectable hydrogel for photothermal therapy in osteoarthritis, focusing on the modulation of the inflammatory environment.
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Data Availability Statement
The data are available from the corresponding author upon reasonable request.
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Funding
This study was supported by the National Natural Science Foundation of China (Grant No. 81902262) (Anmin Chen), Chongqing Natural Science Foundation project (cstc2021jcyj-msmX0529) (Qian Feng) and the National Natural Science Foundation of China (Grant No. 81702687) (Kai Xu). The authors thank the supports of the Experimental Medicine Research Center, Tongji Hospital to this study during the COVID-19 pandemic.
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Zhiyi He: investigation (cell experiments and animal study), methodology, data curation, writing – review & editing; Pengzhen Bu: investigation (Synthesis and detection of hydrogel), data curation, writing – review & editing; Kai Xu: conceptualization, methodology, writing – original draft (supplementary), funding acquisition; Renpeng Peng: animal study, data curation; Wei Xiong: data curation; Peng Cheng: data curation; Jiarui Cui: visualization (graphical illustrations); Anmin Chen: funding acquisition; Haokun Mo: animal study; Xiong Zhang: animal study; Caiqi Cheng: data curation,; Jun Zhou: data curation, supervision; Jiaming Zhang: methodology, investigation (histomorphometric analyses, transcriptomic, bioinformatic analyses, statistics), data curation, visualization (all the figures), writing – original draft (main); Qian Feng: conceptualization, project administration, supervision, resources, funding acquisition, data curation, writing – original draft (supplementary); Zhanggang Wang: project administration, manuscript revision. All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.
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He, Z., Bu, P., Xu, K. et al. Remodeling of the pro-inflammatory microenvironment in osteoarthritis via hydrogel-based photothermal therapy. Adv Compos Hybrid Mater 7, 36 (2024). https://doi.org/10.1007/s42114-024-00835-4
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DOI: https://doi.org/10.1007/s42114-024-00835-4