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Immunoregulation and anti-metalloproteinase bioactive injectable polysalicylate matrixgel for efficiently treating osteoarthritis.

ABSTRACT: Current treatments of osteoarthritis, such as oral medication and intra-articular injections, only provided temporary relief from pain and achieved limited advance in inhibiting progression. The development of new treatments is hindered by the complicated and unclear pathological mechanisms. Oxidative stress and immune inflammation are believed to be the important factors in the induction and progression of osteoarthritis. Herein, this work presents a bioactive material strategy to treat osteoarthritis, based on the FPSOH matrixgel with robust anti-inflammatory activity through inhibiting the oxidative stress and nuclear factor kappa B signaling, preventing the metalloproteinase, as well as inducing M2 polarization of macrophage, thereby providing immune regulation of synovial macrophages and suppressing the progression of synovitis and osteoarthritis. In vivo experiments demonstrated that FPSOH hydrogel can prevent papain-induced osteoarthritis and its progression, and provide dual protection for cartilage and synovium, as compared with commercial sodium hyaluronate.

SUBMITTER: Jia X

PROVIDER: S-EPMC9114689 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Immunoregulation and anti<i>-</i>metalloproteinase bioactive injectable polysalicylate matrixgel for efficiently treating osteoarthritis.

Jia Xinlin X Ma Junping J Chen Xuzhuo X Li Wentao W Zhou Xianhao X Lei Bo B Zhao Xin X Mao Yuanqing Y

Materials today. Bio 20220506

Current treatments of osteoarthritis, such as oral medication and intra-articular injections, only provided temporary relief from pain and achieved limited advance in inhibiting progression. The development of new treatments is hindered by the complicated and unclear pathological mechanisms. Oxidative stress and immune inflammation are believed to be the important factors in the induction and progression of osteoarthritis. Herein, this work presents a bioactive material strategy to treat osteoar ...[more]

PMID: 35601894

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Project description:BackgroundOsteoarthritis (OA) is a degenerative joint disease characterized by the progressive degeneration of articular cartilage, leading to pain, stiffness, and loss of joint function. The pathogenesis of OA involves multiple factors, including increased intracellular reactive oxygen species (ROS), enhanced chondrocyte apoptosis, and disturbances in cartilage matrix metabolism. These processes contribute to the breakdown of the extracellular matrix (ECM) and the loss of cartilage integrity, ultimately resulting in joint damage and dysfunction. RNA interference (RNAi) therapy has emerged as a promising approach for the treatment of various diseases, including hATTR and acute hepatic porphyria. By harnessing the natural cellular machinery for gene silencing, RNAi allows for the specific inhibition of target genes involved in disease pathogenesis. In the context of OA, targeting key molecules such as matrix metalloproteinase-13 (MMP13), which plays a critical role in cartilage degradation, holds great therapeutic potential.ResultsIn this study, we developed an innovative therapeutic approach for OA using a combination of liposome-encapsulated siMMP13 and NG-Monomethyl-L-arginine Acetate (L-NMMA) to form an injectable hydrogel. The hydrogel served as a delivery vehicle for the siMMP13, allowing for sustained release and targeted delivery to the affected joint. Experiments conducted on destabilization of the medial meniscus (DMM) model mice demonstrated the therapeutic efficacy of this composite hydrogel. Treatment with the hydrogel significantly inhibited the degradation of cartilage matrix, as evidenced by histological analysis showing preserved cartilage structure and reduced loss of proteoglycans. Moreover, the hydrogel effectively suppressed intracellular ROS accumulation in chondrocytes, indicating its anti-oxidative properties. Furthermore, it attenuated chondrocyte apoptosis, as demonstrated by decreased levels of apoptotic markers.ConclusionIn summary, the injectable hydrogel containing siMMP13, endowed with anti-ROS and anti-apoptotic properties, may represent an effective therapeutic strategy for osteoarthritis in the future.

Project description:BackgroundParkinson's disease (PD) is one of the most common long-term neurodegenerative diseases. Current treatments for PD are mostly based on surgery and medication because of the limitation and challenges in selecting proper biomaterials. In this study, an injectable bioactive hydrogel based on novel tannic acid crosslinker was developed to treat PD.MethodsThe oxidized tannic acid modified gold nano-crosslinker was synthesized and used to effectively crosslink chitosan for preparation of the bioactive self-healing hydrogel. The crosslinking density, conductivity, self-healing ability, and injectability of the hydrogel were characterized. Abilities of the hydrogel to promote the proliferation and differentiation of neural stem cells (NSCs) were assessed in vitro. Anti-inflammatory property was analyzed on J774A.1 macrophages. The hydrogel was injected in the PD rat model for evaluation of the motor function recovery, electrophysiological performance improvement, and histological repair.ResultsThe hydrogel exhibited self-healing property and 34G (~ 80 μm) needle injectability. NSCs grown in the hydrogel displayed long-term proliferation and differentiation toward neurons in vitro. Besides, the hydrogel owned strong anti-inflammatory and antioxidative capabilities to rescue inflamed NSCs (~ 90%). Brain injection of the bioactive hydrogel recovered the motor function of PD rats. Electrophysiological measurements showed evident alleviation of irregular discharge of nerve cells in the subthalamic nucleus of PD rats administered with the hydrogel. Histological examination confirmed that the hydrogel alone significantly increased the density of tyrosine hydroxylase positive neurons and fibers as well as reduced inflammation, with a high efficacy similar to drug-loaded hydrogel.ConclusionThe new bioactive hydrogel serves as an effective brain injectable implant to treat PD and a promising biomaterial for developing novel strategies to treat brain diseases.

Dataset Information

Immunoregulation and anti-metalloproteinase bioactive injectable polysalicylate matrixgel for efficiently treating osteoarthritis.

Publications

Immunoregulation and anti<i>-</i>metalloproteinase bioactive injectable polysalicylate matrixgel for efficiently treating osteoarthritis.

Similar Datasets

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