Injectable spontaneous hydrogen-releasing hydrogel for long-lasting alleviation of osteoarthritis
Source abstract
Abstract
Excessive production of reactive oxygen species (ROS) amplifies pro-inflammatory pathways and exacerbates immune responses, and is a key factor in the progression of osteoarthritis (OA). Therapeutic hydrogen gas (H2) with antioxidative and anti-inflammatory effects, has a potential for OA alleviation, but the targeted delivery and sustained release of H2 are still challenging. Herein, we develop an injectable calcium boride nanosheets (CBN) loaded hydrogel platform (CBN@GelDA hydrogel) as a high-payload and sustainable H2 precursor for OA treatment. The CBN@GelDA hydrogel could maintain constant physiological pH conditions which further promotes more H2 release than the CBN alone and lasts more than one week. The biocompatibility of this hydrogel with macrophages and chondrocytes is effectively enhanced. The experiments show that the CBN@GelDA hydrogel holds the ROS scavenging ability, reducing the expression of related inflammatory cytokines, lessening M1 macrophages but stimulating M2 phenotype, and thereby decreasing chondrocyte apoptosis, which facilitates to breaking of the vicious circle of OA progression. Furthermore, a single-time injection of the CBN@GelDA hydrogel markedly reduces joint destruction in OA rats. From what has been discussed above, this injectable spontaneous H2-releasing hydrogel is promising for OA treatment. STATEMENT OF SIGNIFICANCE: Oxidative stress and inflammation play the key role in the occurrence and development of osteoarthritis (OA). The system of a hydrogel loaded with H2 precursor calcium boride nanosheet (CBN), which is the first to use as an H2 precursor, integrates superior injectable and biocompatible of hydrogel and the selection of antioxidant properties of H2. This system can improve H2 release behavior and achieve a single injection into the articular cavity to alleviate the progression of OA in rats. This study of the combination of a convenient long-acting injectable hydrogel and a safe therapeutic gas is of great value for improving the quality of life of clinical patients.
Source: europepmc · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Hydrogen's biological and therapeutic effects · Sulfur Compounds in Biology · Biochemical effects in animals
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (73)
Show source-provided references
1. Advances in osteoarthritis research in 2021 and beyond
2. Precise targeting of miR-141/200c cluster in chondrocytes attenuates osteoarthritis development10.1136/annrheumdis-2020-218469 ↗
3. Emerging regulators of the inflammatory process in osteoarthritis10.1038/nrrheum.2014.162 ↗
4. Osteoarthritis10.1038/nrdp.2016.72 ↗
5. Osteoarthritis: a complicated joint disease requiring extensive studies with multiple approaches
6. An osteoarthritis subtype characterized by synovial lipid metabolism disorder and fibroblast-like synoviocyte dysfunction
7. Molecular signaling in temporomandibular joint osteoarthritis
8. Recent progress in cartilage lubrication10.1002/adma.202005513 ↗
9. Injectable polymeric nanoparticle hydrogel system for long-term anti-inflammatory effect to treat osteoarthritis
10. Design of therapeutic biomaterials to control inflammation10.1038/s41578-022-00426-z ↗
11. In situ nanoreactor for photosynthesizing H2 gas to mitigate oxidative stress in tissue inflammation10.1021/jacs.7b07492 ↗
12. Mitochondrial DNA variation and the pathogenesis of osteoarthritis phenotypes10.1038/s41584-018-0001-0 ↗
13. Hydrogen gas from inflammation treatment to cancer therapy10.1021/acsnano.9b05124 ↗
14. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals10.1038/nm1577 ↗
15. Hydrogen rich water prevents progression of NASH and accompanying hepatic tumorigenesis in mice10.1016/S0016-5085(11)62920-X ↗
16. Hydrogen: another gas with therapeutic potential10.1038/ki.2009.432 ↗
17. Hydrogen-powered microswimmers for precise and active hydrogen therapy towards acute ischemic stroke
18. Magnesium-based micromotors as hydrogen generators for precise rheumatoid arthritis therapy10.1021/acs.nanolett.0c04438 ↗
19. Magnesium-based micromotors for enhanced active and synergistic hydrogen chemotherapy
20. Acid-degradable hydrogen-generating metal-organic framework for overcoming cancer resistance/metastasis and off-target side effects10.1002/advs.202101965 ↗
21. Acid-responsive H2-releasing 2D MgB2 nanosheet for therapeutic synergy and side effect attenuation of gastric cancer chemotherapy
22. Intratumoral high-payload delivery and acid-responsive release of H-2 for efficient cancer therapy using the ammonia borane-loaded mesoporous silica nanomedicine10.1016/j.apmt.2018.01.008 ↗
23. Local generation of hydrogen for enhanced photothermal therapy10.1038/s41467-018-06630-2 ↗
24. Porphyrin-palladium hydride MOF nanoparticles for tumor-targeting photoacoustic imaging-guided hydrogenothermal cancer therapy10.1039/C9NH00021F ↗
25. Protective effects of hydrogen-rich water against cartilage damage in a rat model of osteoarthritis by inhibiting oxidative stress, matrix catabolism, and apoptosis10.12659/MSM.920211 ↗
26. Hydrogen (H2) alleviates osteoarthritis by inhibiting apoptosis and inflammation via the jnk signaling pathway10.2147/JIR.S297622 ↗
27. An in situ depot for continuous evolution of gaseous h-2 mediated by a magnesium passivation/activation cycle for treating osteoarthritis10.1002/anie.201806159 ↗
28. Molecular hydrogen as a preventive and therapeutic medical gas: initiation, development and potential of hydrogen medicine10.1016/j.pharmthera.2014.04.006 ↗
29. MBene as a theranostic nanoplatform for photocontrolled intratumoral retention and drug release
30. Coordination-induced exfoliation to monolayer Bi-anchored MnB2 nanosheets for multimodal imaging-guided photothermal therapy of cancer10.7150/thno.39715 ↗
31. Controllable decomposition of Ca(BH4)2 for reversible hydrogen storage10.1039/C7CP00448F ↗
32. A novel strategy for reversible hydrogen storage in Ca(BH4)210.1039/C5CC03605D ↗
33. Process analysis and mechanism investigation of low temperature synthesis of nanoscale calcium hexaboride powder10.1166/jnn.2014.9404 ↗
34. Effect of addition of B2O3 to the sol-gel synthesized 45S5 bioglass
35. The role of oxidative stress, renal inflammation, and apoptosis in post ischemic reperfusion injury of kidney tissue: the protective effect of dose-dependent boric acid administration10.1007/s12011-019-01824-1 ↗
36. Engineering robust Ag-decorated polydopamine nano-photothermal platforms to combat bacterial infection and prompt wound healing10.1002/advs.202106015 ↗
37. Stem cell–homing hydrogel-based miR-29b-5p delivery promotes cartilage regeneration by suppressing senescence in an osteoarthritis rat model10.1126/sciadv.abk0011 ↗
38. Anti-friction MSCs delivery system improves the therapy for severe osteoarthritis10.1002/adma.202104758 ↗
39. Injectable hydrogel with nucleus pulposus-matched viscoelastic property prevents intervertebral disc degeneration
40. Recent advances in design of functional biocompatible hydrogels for bone tissue engineering
41. Polydopamine nanoparticle-dotted food gum hydrogel with excellent antibacterial activity and rapid shape adaptability for accelerated bacteria-infected wound healing
42. Nanocomposite multifunctional hydrogel for suppressing osteosarcoma recurrence and enhancing bone regeneration
43. Tough, self-healable and tissue-adhesive hydrogel with tunable multifunctionality10.1038/am.2017.33 ↗
44. Mussel-inspired extracellular matrix-mimicking hydrogel scaffold with high cell affinity and immunomodulation ability for growth factor-free cartilage regeneration
45. Charge-guided micro/nano-hydrogel microsphere for penetrating cartilage matrix10.1002/adfm.202107678 ↗
46. A biomimetic mussel-inspired ε-poly-l-lysine hydrogel with robust tissue-anchor and anti-infection capacity
47. Injectable enzymatically crosslinked hydrogel system with independent tuning of mechanical strength and gelation rate for drug delivery and tissue engineering10.1039/b926456f ↗
48. Modulation of chondrocyte functions and stiffness-dependent cartilage repair using an injectable enzymatically crosslinked hydrogel with tunable mechanical properties10.1016/j.biomaterials.2013.11.070 ↗
49. Situ forming and H2O2‑releasing hydrogels for treatment of drug-resistant bacterial infections10.1021/acsami.7b03870 ↗
50. Supramolecular metallo-bioadhesive for minimally invasive use10.1002/adma.201602606 ↗
51. Multifunctional injectable hydrogel dressings for effectively accelerating wound healing: enhancing biomineralization strategy
52. A mussel-inspired double-crosslinked tissue adhesive intended for internal medical use10.1016/j.actbio.2016.02.003 ↗
53. An engineered cell-laden adhesive hydrogel promotes craniofacial bone tissue regeneration in rats10.1126/scitranslmed.aay6853 ↗
54. Capturing magnesium ions via microfluidic hydrogel microspheres for promoting cancellous bone regeneration10.1021/acsnano.1c02147 ↗
55. Bioinspired, injectable, tissue-adhesive and antibacterial hydrogel for multiple tissue regeneration by minimally invasive therapy
56. A multifunctional anti-inflammatory drug that can specifically target activated macrophages, massively deplete intracellular H2O2, and produce large amounts CO for a highly efficient treatment of osteoarthritis10.1016/j.biomaterials.2020.120155 ↗
57. Kinsenoside attenuates osteoarthritis by repolarizing macrophages through inactivating NF-κB/MAPK signaling and protecting chondrocytes10.1016/j.apsb.2019.01.015 ↗
58. Histology, glycosaminoglycan level and cartilage stiffness in monoiodoacetate-induced osteoarthritis: comparative analysis with anterior cruciate ligament transection in rat model and human osteoarthritis10.7150/ijms.6964 ↗
59. Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. II. Correlation of morphology with biochemical and metabolic data10.2106/00004623-197153030-00009 ↗
60. Artificial M2 macrophages for disease-modifying osteoarthritis therapeutics10.1016/j.biomaterials.2021.120865 ↗
61. Enzymatically crosslinked alginate hydrogels with improved adhesion properties10.1039/C4PY01757A ↗
62. Dual-crosslinked dynamic hydrogel incorporating {Mo154} with pH and NIR responsiveness for chemo-photothermal therapy
63. Injectable natural polymer hydrogels for treatment of knee osteoarthritis
64. Injectable hydrogel microspheres with self-renewable hydration layers alleviate osteoarthritis10.1126/sciadv.abl6449 ↗
65. Redox and NF-κB signaling in osteoarthritis10.1016/j.freeradbiomed.2018.09.025 ↗
66. Cartilage-targeting peptide-modified dual-drug delivery nanoplatform with NIR laser response for osteoarthritis therapy
67. A sweet spot for macrophages: focusing on polarization10.1016/j.phrs.2021.105576 ↗
68. Structural transformative antioxidants for dual-responsive anti-inflammatory delivery and photoacoustic inflammation imaging10.1002/anie.202100873 ↗
69. ROS-responsive boronate-stabilized polyphenol–poloxamer 188 assembled dexamethasone nanodrug for macrophage repolarization in osteoarthritis treatment10.1002/adhm.202100883 ↗
70. A smart ROS/NIR dual-responsive melanin delivery platform for photoacoustic imaging-guided osteoarthritis therapy
71. Agkistrodon ameliorates pain response and prevents cartilage degradation in monosodium iodoacetate-induced osteoarthritic rats by inhibiting chondrocyte hypertrophy and apoptosis10.1016/j.jep.2018.12.004 ↗
72. Runx2 plays a central role in osteoarthritis development
73. Differential roles of TGF-beta signalling in joint tissues during osteoarthritis development10.1136/annrheumdis-2016-210312 ↗