Carrier rocket-inspired hydrogel microspheres targeting subchondral bone osteoclast activity alleviate osteoarthritic pain and cartilage degeneration
Abstract 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...
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2025-08-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03598-2 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Zhenglin Zhu |
| collection | DOAJ |
| description | Abstract 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 |
| format | Article |
| id | doaj-art-5ebb18cdaac74cea95eb7943514bc3c6 |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-5ebb18cdaac74cea95eb7943514bc3c62025-08-20T04:02:55ZengBMCJournal of Nanobiotechnology1477-31552025-08-0123111810.1186/s12951-025-03598-2Carrier rocket-inspired hydrogel microspheres targeting subchondral bone osteoclast activity alleviate osteoarthritic pain and cartilage degenerationZhenglin Zhu0Yujia Luo1Pengcheng Xiao2Yi Xie3Jun Zhang4Ke Huang5Xiangdong Wu6Ke Lu7Yuting Zhang8Jianye Tan9Hong Chen10Wei Huang11Yiting Lei12Junyi Liao13Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Orthopaedic Surgery, Beijing Jishuitan Hospital, Capital Medical University, Fourth Clinical College of Peking University, National Center for OrthopaedicsShenzhen Hospital, Southern Medical UniversityResearch Center for Computer-aided Drug Discovery, Shenzhen Institute of Advanced Technology, Chinese Academy of SciencesDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical UniversityAbstract 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 Abstracthttps://doi.org/10.1186/s12951-025-03598-2OsteoarthritisPolyamidoamineHydrogel microspheresPain therapyCartilage degeneration |
| spellingShingle | 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 Carrier rocket-inspired hydrogel microspheres targeting subchondral bone osteoclast activity alleviate osteoarthritic pain and cartilage degeneration Journal of Nanobiotechnology Osteoarthritis Polyamidoamine Hydrogel microspheres Pain therapy Cartilage degeneration |
| title | Carrier rocket-inspired hydrogel microspheres targeting subchondral bone osteoclast activity alleviate osteoarthritic pain and cartilage degeneration |
| title_full | Carrier rocket-inspired hydrogel microspheres targeting subchondral bone osteoclast activity alleviate osteoarthritic pain and cartilage degeneration |
| title_fullStr | Carrier rocket-inspired hydrogel microspheres targeting subchondral bone osteoclast activity alleviate osteoarthritic pain and cartilage degeneration |
| title_full_unstemmed | Carrier rocket-inspired hydrogel microspheres targeting subchondral bone osteoclast activity alleviate osteoarthritic pain and cartilage degeneration |
| title_short | Carrier rocket-inspired hydrogel microspheres targeting subchondral bone osteoclast activity alleviate osteoarthritic pain and cartilage degeneration |
| title_sort | carrier rocket inspired hydrogel microspheres targeting subchondral bone osteoclast activity alleviate osteoarthritic pain and cartilage degeneration |
| topic | Osteoarthritis Polyamidoamine Hydrogel microspheres Pain therapy Cartilage degeneration |
| url | https://doi.org/10.1186/s12951-025-03598-2 |
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