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Nature Communications · 2023 ·Vol. 14 ·期 1 ·1-11 · IF 16.6

Bone disease imaging through the near-infrared-II window

Mi Chao,Zhang Xun,Yang Chengyu,Wu Jianqun,Chen Xinxin,Ma Chenguang,Wu Sitong,Yang Zhichao,Qiao Pengzhen,Liu Yang,Wu Weijie,Guo Zhiyong,Liao Jiayan,Zhou Jiajia,Guan Ming,Liang Chao,Liu Chao,Jin Dayong

Skeletal disorders are commonly diagnosed by X-ray imaging, but the radiation limits its use. Optical imaging through the near-infrared-II window (NIR-II, 1000–1700 nm) can penetrate deep tissues without radiation risk, but the targeting of contrast agent is non-specific. Here, we report that lanthanide-doped nanocrystals can passively target the bone marrow, which can be effective for over two months. We therefore develop the high-resolution NIR-II imaging method for bone disease diagnosis, including the 3D bone imaging instrumentation to show the intravital bone morphology. We demonstrate the monitoring of 1 mm bone defects with spatial resolution comparable to the X-ray imaging result. Moreover, NIR-II imaging can reveal the early onset inflammation as the synovitis in the early stage of rheumatoid arthritis, comparable to micro computed tomography (μCT) in diagnosis of osteoarthritis, including the symptoms of osteophyte and hyperostosis in the knee joint.

研究领域: 医学成像 · 生物医学工程 · 骨科 · 纳米技术
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Materials Today Bio · 2024 · IF 8.7

Injectable nanocomposite hydrogels with enhanced lubrication and antioxidant properties for the treatment of osteoarthritis

Qizhu Chen,Yuxin Jin,Tao Chen,Hao Zhou,Xinzhou Wang,Ouqiang Wu,Linjie Chen,Zhiguang Zhang,Zhengyu Guo,Jin Sun,Aimin Wu,Qiuping Qian

Osteoarthritis (OA) is a chronic inflammatory joint disease characterized by progressive cartilage degeneration, synovitis, and osteoid formation. In order to effectively treat OA, it is important to block the harmful feedback caused by reactive oxygen species (ROS) produced during joint wear. To address this challenge, we have developed injectable nanocomposite hydrogels composed of polygallate-Mn (PGA-Mn) nanoparticles, oxidized sodium alginate, and gelatin. The inclusion of PGA-Mn not only enhances the mechanical strength of the biohydrogel through a Schiff base reaction with gelatin but also ensures efficient ROS scavenging ability. Importantly, the nanocomposite hydrogel exhibits excellent biocompatibility, allowing it to effectively remove ROS from chondrocytes and reduce the expression of inflammatory factors within the joint. Additionally, the hygroscopic properties of the hydrogel contribute to reduced intra-articular friction and promote the production of cartilage-related proteins, supporting cartilage synthesis. In vivo experiments involving the injection of nanocomposite hydrogels into rat knee joints with an OA model have demonstrated successful reduction of osteophyte formation and protection of cartilage from wear, highlighting the therapeutic potential of this approach for treating OA.

研究领域: 生物材料 · 纳米技术 · 骨科 · 药学
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JOURNAL OF CELLULAR AND MOLECULAR MEDICINE · 2021 ·Vol. 25 ·期 15 ·7472-7484 · IF 5.31

Recombinant platelet-derived growth factor-BB alleviates osteoarthritis in a rat model by decreasing chondrocyte apoptosis in vitro and in vivo

Pengfei Zhu,Zhengchao Wang,Zhenxing Sun,Bokai Liao,Yu Cai

Osteoarthritis (OA) is a common joint disease that mainly affects the diarthrodial joints. Treatments for OA include non-pharmacological interventions, topical and oral therapies, intra-articular therapies and joint surgery. However, all the treatments mentioned above mainly aim to control the symptoms instead of improving or reversing the joint condition. In this research, we observed the effect of recombinant platelet-derived growth factor (PDGF)-BB on OA in a monosodium iodoacetate (MIA)–induced rat model and revealed the possible mechanisms. In vitro, the level of inflammation in the chondrocytes was gradually alleviated, and the apoptosis rate was gradually decreased by PDGF-BB at increasing concentrations. The levels of p-p38, Bax and caspase-3 decreased, and the level of p-Erk increased with increasing PDGF-BB concentration. In vivo, PDGF-BB could significantly reverse chondrocyte and matrix loss. Furthermore, high concentrations of PDGF-BB could alleviate cartilage hyperplasia to remodel the tissue. The level of collagen II was up-regulated, and the levels of collagen X and apoptosis were down-regulated by increasing concentrations of PDGF-BB. In conclusion, recombinant PDGF-BB alleviated OA by down-regulating caspase-3-dependent apoptosis. The effects of PDGF-BB on OA mainly include inhibiting chondrocyte loss, reducing cartilage hyperplasia and osteophyte formation, and regulating collagen anabolism.

研究领域: 骨科 · 分子生物学 · 细胞生物学 · 药理学
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JOURNAL OF NANOBIOTECHNOLOGY · 2025 ·Vol. 23 ·期 1 ·1-21 · IF 12.6

A ROS-responsive hydrogel encapsulated with matrix metalloproteinase-13 siRNA nanocarriers to attenuate osteoarthritis progression

Wang Qiuyang,Feng Kai,Wan Guangsheng,Liao Wei,Jin Jing,Wang Peng,Sun Xiaolian,Wang Weijun,Jiang Qing

RNA interference (RNAi) and oxidative stress inhibition therapeutic strategies have been extensively utilized in the treatment of osteoarthritis (OA), the most prevalent degenerative joint disease. However, the synergistic effects of these approaches on attenuating OA progression remain largely unexplored. In this study, matrix metalloproteinase-13 siRNA (siMMP-13) was incorporated onto polyethylenimine (PEI)-polyethylene glycol (PEG) modified Fe3O4 nanoparticles, forming a nucleic acid nanocarrier termed si-Fe NPs. Subsequently, a poly(vinyl alcohol) (PVA) crosslinked phenylboronic acid (PBA)-modified hyaluronic acid (HA) hydrogel (HPP) was used to encapsulate the si-Fe NPs, resulting in a bifunctional hydrogel (si-Fe-HPP) with reactive oxygen species (ROS)-responsive and RNAi therapeutic properties. Studies in vitro demonstrated that si-Fe-HPP exhibited excellent biocompatibility, anti-inflammatory effects and prolonged stable retention time in knee joint. Intra-articular injection of si-Fe-HPP significantly attenuated cartilage degradation in mice with destabilization of the medial meniscus (DMM)-induced OA. The si-Fe-HPP treatment not only notably alleviated synovitis, osteophyte formation and subchondral bone sclerosis, but also markedly improved physical activity and reduced pain in DMM-induced OA mice. This study reveals that si-Fe-HPP, with its ROS-responsive and RNAi abilities, can significantly protect chondrocytes and attenuate OA progression, providing novel insights and directions for the development of therapeutic materials for OA treatment.Graphical

研究领域: 生物材料 · 纳米技术 · 骨科 · 分子生物学 · 治疗学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2024 · IF 7.7

Nanozyme-enhanced injectable hyaluronic acid-based hydrogel for the treatment of osteoarthritis

Hui Wang,Zuhao Li,Jiaqi Liu,Haoran Chang,Jincheng Wang,Shanliang Song,Yue Zhao,Xin Zhao

The progression of osteoarthritis (OA) is dramatically accelerated by excessive reactive oxygen species (ROS)-induced apoptosis of chondrocytes and the inflammatory response of synovial macrophages. In this study, we developed an injectable hydrogel with a catalase-mimicking nanozyme activity as a therapeutic agent for OA. In vitro experiments confirmed that the HA and peroxide-mimetic nanoenzyme-enhanced hydrogel, containing ε-polylysine/Mn 1.8 Co 1.2 O 4 (ε-PLE/MnCoO) nanoparticles, continuously eliminated ROS and inflammatory cytokines while promoting the polarization of inflammatory macrophages (M1 phenotype) towards anti-inflammatory macrophages (M2 phenotype) in dysfunctional microenvironments. When used for intraarticular injections in OA models, the nanoenzyme-enhanced hydrogel effectively reduced oxidative stress by scavenging ROS and regulating the immune microenvironment. It resulted in a subsequent reduction in the expression of inflammatory factors, including MMP-13, TNF-α, IL-1β, and iNOS in both the synovium and joint fluid. Moreover, cartilage repair was enhanced by the promotion of COL-2 and SOX-9 expression in the cartilage tissue, whereas osteophyte formation in OA was reduced. This study introduced an innovative treatment strategy for the clinical management of OA, demonstrating its significant potential for application in treating OA.

研究领域: 生物医学工程 · 骨科 · 纳米技术 · 药理学
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