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Background <p>Osteoarthritis (OA) represents a major global health challenge, characterized by progressive cartilage degeneration and subchondral bone remodeling, which culminate in debilitating pain and functional impairment. While recent studies have underscored the pivotal role of activated osteoclasts in the pathogenesis of OA and its associated pain, the therapeutic potential of intra-articular drug delivery has been hindered by challenges such as rapid synovial clearance and the poor permeability of cartilage, limiting the effective inhibition of subchondral osteoclast activity.</p> Methods <p>Sixth generation polyamidoamine (PAMAM) dendrimers were used to delivery pamidronate disodium (PD) penetrating cartilage (PD@PM). PD@PM was loaded in aldehyde modified hyaluronic acid methacrylate (AHAMA) (PD@PM@MG), to facilitating the joint injection and conglutinating on the cartilage. Therapeutic effects of PD@PM@MG were validated by in vitro and in vivo OA models.</p> Results <p>PD@PM@MGs microspheres are uniformly distributed across the cartilage surface and sustained releasing of PD-loaded PAMAM. The positively charged PD-loaded PAMAM (&lt; 10&#xa0;nm) efficiently permeates the cartilage matrix, neutralizes damage-associated molecular patterns, and effectively inhibits subchondral osteoclasts activities. Mice OA model tests demonstrated that intra-articular injection of PD@PM@MGs markedly alleviated arthritic pain, mitigated cartilage degeneration, and attenuated subchondral bone remodeling.</p> Conclusions <p>The intra-articular injection of PD@PM@MGs significantly alleviates OA symptoms and progression, offering a novel direction for clinical OA intervention.</p> Graphical Abstract <p></p>

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Carrier rocket-inspired hydrogel microspheres targeting subchondral bone osteoclast activity alleviate osteoarthritic pain and cartilage degeneration

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年8月4日

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  • Zhenglin Zhu,
  • Yujia Luo,
  • Pengcheng Xiao,
  • Yi Xie,
  • Jun Zhang,
  • Ke Huang,
  • Xiangdong Wu,
  • Ke Lu,
  • Yuting Zhang,
  • Jianye Tan,
  • Hong Chen,
  • Wei Huang,
  • Yiting Lei,
  • Junyi Liao

摘要

Background

Osteoarthritis (OA) represents a major global health challenge, characterized by progressive cartilage degeneration and subchondral bone remodeling, which culminate in debilitating pain and functional impairment. While recent studies have underscored the pivotal role of activated osteoclasts in the pathogenesis of OA and its associated pain, the therapeutic potential of intra-articular drug delivery has been hindered by challenges such as rapid synovial clearance and the poor permeability of cartilage, limiting the effective inhibition of subchondral osteoclast activity.

Methods

Sixth generation polyamidoamine (PAMAM) dendrimers were used to delivery pamidronate disodium (PD) penetrating cartilage (PD@PM). PD@PM was loaded in aldehyde modified hyaluronic acid methacrylate (AHAMA) (PD@PM@MG), to facilitating the joint injection and conglutinating on the cartilage. Therapeutic effects of PD@PM@MG were validated by in vitro and in vivo OA models.

Results

PD@PM@MGs microspheres are uniformly distributed across the cartilage surface and sustained releasing of PD-loaded PAMAM. The positively charged PD-loaded PAMAM (< 10 nm) efficiently permeates the cartilage matrix, neutralizes damage-associated molecular patterns, and effectively inhibits subchondral osteoclasts activities. Mice OA model tests demonstrated that intra-articular injection of PD@PM@MGs markedly alleviated arthritic pain, mitigated cartilage degeneration, and attenuated subchondral bone remodeling.

Conclusions

The intra-articular injection of PD@PM@MGs significantly alleviates OA symptoms and progression, offering a novel direction for clinical OA intervention.

Graphical Abstract