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<p>Osteoarthritis (OA) involves multiple pathological processes and presents significant clinical challenges in treatment. Traditional therapies focus on individual factors in cartilage, synovium, or subchondral bone, limiting their ability to comprehensively address OA pathogenesis. In this study, a ROS/MMP13 dual-responsive organic selenium hydrogel microsphere (HSPHR) is developed to trigger a localized microenvironmental response specific to early OA by exploiting the disease’s pathological features. Simultaneously, the organic selenium component effectively enhances selenoprotein levels in cartilage, synovium, and subchondral bone, enabling multimodal treatment for osteoarthritis. HSPHR injections into joints reduce cartilage damage, synovial hyperplasia, and bone sclerosis in post-traumatic OA, while promoting new cartilage in defect models. It enhances selenoprotein synthesis and activates the PI3K-AKT-mTOR pathway in key cells, improving mitochondrial function and antioxidant capacity, thus reversing OA-related changes. Here, we present a multimodal therapeutic strategy for OA lesions and reveal shared regulatory pathways among different cell types. This approach offers distinct insights for the multimodal treatment of degenerative joint diseases.</p>

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Organic di-selenide hydrogel microspheres for multimodal treatment of osteoarthritis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月3日

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  • Yang Liu,
  • Yijian Zhang,
  • Chenqi Yu,
  • Xiaowei Xia,
  • Kang Kang,
  • Yubin Wu,
  • Yaoge Deng,
  • Jianfeng Yu,
  • Mingzhuang Hou,
  • Zhiwen Luo,
  • Huilin Yang,
  • Yong Xu,
  • Xuesong Zhu

摘要

Osteoarthritis (OA) involves multiple pathological processes and presents significant clinical challenges in treatment. Traditional therapies focus on individual factors in cartilage, synovium, or subchondral bone, limiting their ability to comprehensively address OA pathogenesis. In this study, a ROS/MMP13 dual-responsive organic selenium hydrogel microsphere (HSPHR) is developed to trigger a localized microenvironmental response specific to early OA by exploiting the disease’s pathological features. Simultaneously, the organic selenium component effectively enhances selenoprotein levels in cartilage, synovium, and subchondral bone, enabling multimodal treatment for osteoarthritis. HSPHR injections into joints reduce cartilage damage, synovial hyperplasia, and bone sclerosis in post-traumatic OA, while promoting new cartilage in defect models. It enhances selenoprotein synthesis and activates the PI3K-AKT-mTOR pathway in key cells, improving mitochondrial function and antioxidant capacity, thus reversing OA-related changes. Here, we present a multimodal therapeutic strategy for OA lesions and reveal shared regulatory pathways among different cell types. This approach offers distinct insights for the multimodal treatment of degenerative joint diseases.