MXene-Based Photothermal-Responsive Injectable Hydrogel Microsphere Modulates Physicochemical Microenvironment to Alleviate Osteoarthritis

Abstract

Osteoarthritis (OA) is a physical lubrication microenvironment-inadequate disease accompanied by a sustained chronic chemical inflammation microenvironment and the progression of articular cartilage destruction. Despite the promising OA treatment outcomes observed in the enhancement of lubrication inspired by ball bearings to reduce friction and support loads, the therapeutic effect of near-infrared (NIR) irradiation-based photothermal-responsive controlled release “smart hydrogel microspheres” on OA remains unclear. Here, we prepared MXene/NIPIAM-based photothermal-responsive injectable hydrogel microspheres encapsulating diclofenac sodium using a microfluidic system. Consequently, NIR irradiation-based photothermal-responsive controlled release “smart hydrogel microspheres” demonstrate beneficial therapeutic effects in the treatment of OA by modulating the physical lubrication and chemical chronic inflammation microenvironment, laying the foundation for the application of smart hydrogel microsphere delivery systems loaded with bioactive factors (including agents, cells, and factors) to regulate multiple pathological microenvironments in regenerative medicine.

Keywords

hydrogel microspheres / near-infrared irradiation / osteoarthritis / photothermal-responsive

References

[1] L. Tong, H. Yu, X. Huang, et al., “Current Understanding of Osteoarthritis Pathogenesis and Relevant New Approaches,” Bone Research 10 (2022): 60.

[2] E. Sanchez-Lopez, R. Coras, A. Torres, N. E. Lane, and M. Guma, “Synovial Inflammation in Osteoarthritis Progression,” Nature Reviews Rheumatology 18 (2022): 258–275.

[3] T. Vos, S. S. Lim, C. Abbafati, et al., “Global Burden of 369 Diseases and Injuries in 204 Countries and Territories, 1990-2019: A Systematic Analysis for the Global Burden of Disease Study 2019,” Lancet 396 (2020): 1204–1222.

[4] Q. Yao, X. Wu, C. Tao, et al., “Osteoarthritis: Pathogenic Signaling Pathways and Therapeutic Targets,” Signal Transduction and Targeted Therapy 8 (2023): 56.

[5] M. Basso, E. Arnaldi, A. A. M. Bruno, and M. Formica, “Outcomes of Cementless Fixation in Medial Unicompartmental Knee Arthroplasty: Review of Recent Literature,” Musculoskeletal Surgery 105 (2021): 131–138.

[6] H. Zhang, L. Blunt, X. Jiang, L. Brown, and S. Barrans, “The Significance of the Micropores at the Stem-Cement Interface in Total Hip Replacement,” Journal of Biomaterials Science 22 (2011): 845–856.

[7] S. Bindu, S. Mazumder, and U. Bandyopadhyay, “Non-Steroidal Anti-Inflammatory Drugs (Nsaids) and Organ Damage: A Current Perspective,” Biochemical Pharmacology 180 (2020): 114147.

[8] L. Kock, C. C. van Donkelaar, and K. Ito, “Tissue Engineering of Functional Articular Cartilage: The Current Status,” Cell and Tissue Research 347 (2012): 613–627.

[9] I. A. Jones, R. Togashi, M. L. Wilson, N. Heckmann, and C. T. Vangsness, “Intra-Articular Treatment Options for Knee Osteoarthritis,” Nature Reviews Rheumatology 15 (2019): 77–90.

[10] T. E. McAlindon, M. S. Harkey, R. J. Ward, M. C. Hochberg, and J. B. Driban, “Intra-Articular Corticosteroid Injections in the Hip and Knee: Perhaps Not as Dangerous as They Want You to Believe,” Radiology 295 (2020): 249–250.

[11] J. Knoop, J. Dekker, J. P. Klein, et al., “Biomechanical Factors and Physical Examination Findings in Osteoarthritis of the Knee: Associations With Tissue Abnormalities Assessed by Conventional Radiography and High-Resolution 3.0 Tesla Magnetic Resonance Imaging,” Arthritis Research & Therapy 14 (2012): R212.

[12] W. Zhao, H. Wang, Y. Han, H. Wang, Y. Sun, and H. Zhang, “Dopamine/Phosphorylcholine Copolymer as an Efficient Joint Lubricant and Ros Scavenger for the Treatment of Osteoarthritis,” ACS Applied Materials & Interfaces 12 (2020): 51236–51248.

[13] C. Xie, Q. Sun, Y. Dong, et al., “Calcitriol-Loaded Multifunctional Nanospheres With Superlubricity for Advanced Osteoarthritis Treatment,” ACS Nano 17 (2023): 12842–12861.

[14] S. Bowman, M. E. Awad, M. W. Hamrick, M. Hunter, and S. Fulzele, “Recent Advances in Hyaluronic Acid Based Therapy for Osteoarthritis,” Clinical and Translational Medicine 7 (2018): 6.

[15] H. Yuan, L. L. E. Mears, Y. Wang, et al., “Lubricants for Osteoarthritis Treatment: From Natural to Bioinspired and Alternative Strategies,” Advances in Colloid and Interface Science 311 (2023): 102814.

[16] W. Zhao, Y. Zhang, X. Zhao, et al., “Bioinspired Design of a Cartilage-Like Lubricated Composite With Mechanical Robustness,” ACS Applied Materials & Interfaces 14 (2022): 9899–9908.

[17] A. W. Rutjes, P. Jüni, B. R. da Costa, S. Trelle, E. Nüesch, and S. Reichenbach, “Viscosupplementation for Osteoarthritis of the Knee: A Systematic Review and Meta-Analysis,” Annals of Internal Medicine 157 (2012): 180–191.

[18] C. J. Bell, L. M. Carrick, J. Katta, et al., “Self-Assembling Peptides as Injectable Lubricants for Osteoarthritis,” Journal of Biomedical Materials Research Part A 78 (2006): 236–246.

[19] J. Yang, Y. Han, J. Lin, et al., “Ball-Bearing-Inspired Polyampholyte-Modified Microspheres as Bio-Lubricants Attenuate Osteoarthritis,” Small 16 (2020): 2004519.

[20] Y. Lei, Y. Wang, J. Shen, et al., “Injectable Hydrogel Microspheres With Self-Renewable Hydration Layers Alleviate Osteoarthritis,” Science Advances 8 (2022): eabl6449.

[21] C. Du, Z. Chen, S. Liu, et al., “Lubricin-Inspired Nanozymes Reconstruct Cartilage Lubrication System With an ‘In-Out’ Strategy,” Small Methods 8 (2024): 2400757.

[22] R. Altman, B. Bosch, K. Brune, P. Patrignani, and C. Young, “Advances in NSAID Development: Evolution of Diclofenac Products Using Pharmaceutical Technology,” Drugs 75 (2015): 859–877.

[23] V. Tieppo Francio, S. Davani, C. Towery, and T. L. Brown, “Oral versus Topical Diclofenac Sodium in the Treatment of Osteoarthritis,” Journal of Pain & Palliative Care Pharmacotherapy 31 (2017): 113–120.

[24] Z. Sun, C. Song, J. Zhou, et al., “Rapid Photothermal Responsive Conductive Mxene Nanocomposite Hydrogels for Soft Manipulators and Sensitive Strain Sensors,” Macromolecular Rapid Communications 42 (2021): 2100499.

[25] Y. Huang, Z. Li, K. Hou, et al., “Photothermally Responsive and Durable Polydopamine-Modified MXene-PNIPAM Hydrogels for Smart Friction Regulation,” Tribology International 193 (2024): 109435.

[26] P. Wu, C. Zeng, J. Guo, G. Liu, F. Zhou, and W. Liu, “Achieving Near-Infrared-Light-Mediated Switchable Friction Regulation on MXene-Based Double Network Hydrogels,” Friction 12 (2024): 39–51.

[27] Y. Zhao, Z. You, D. Xing, et al., “Comparison of Chondrocytes in Knee Osteoarthritis and Regulation by Scaffold Pore Size and Stiffness,” Tissue Engineering Part A 27 (2021): 223–236.

[28] L. Chen, K. Peng, H. Huang, et al., “Injectable Hydrogel Based on Enzymatic Initiation of Keratin Methacrylate for Controlled Exosome Release in Intervertebral Disc Degeneration Therapy,” Advanced Functional Materials 34 (2024): 2316545.

[29] T. Gai, Y. Zhang, G. Li, et al., “Engineered Hydrogel Microspheres for Spheroids and Organoids Construction,” Chemical Engineering Journal 498 (2024): 155131.

[30] R. Pareja Tello, S. Wang, F. Fontana, et al., “Fabrication of Hydrogel Microspheres via Microfluidics Using Inverse Electron Demand Diels-Alder Click Chemistry-Based Tetrazine-Norbornene for Drug Delivery and Cell Encapsulation Applications,” Biomaterials Science 11 (2023): 4972–4984.

[31] D. Liu, H. Zhang, F. Fontana, J. T. Hirvonen, and H. A. Santos, “Microfluidic-Assisted Fabrication of Carriers for Controlled Drug Delivery,” Lab on a Chip 17 (2017): 1856–1883.

[32] Z. Wei, S. Wang, J. Hirvonen, H. A. Santos, and W. Li, “Microfluidics Fabrication of Micrometer-Sized Hydrogels With Precisely Controlled Geometries for Biomedical Applications,” Advanced Healthcare Materials 11 (2022): 2200846.

[33] F. Topuz and T. Uyar, “Advances in the Development of Cyclodextrin-Based Nanogels/Microgels for Biomedical Applications: Drug Delivery and beyond,” Carbohydrate Polymers 297 (2022): 120033.

[34] X. Yao, Z. Gong, W. Yin, et al., “Islet Cell Spheroids Produced by a Thermally Sensitive Scaffold: A New Diabetes Treatment,” Journal of Nanobiotechnology 22 (2024): 657.

[35] A. J. Convertine, B. S. Lokitz, Y. Vasileva, et al., “Direct Synthesis of Thermally Responsive DMA/NIPAM Diblock and DMA/NIPAM/DMA Triblock Copolymers Via Aqueous, Room Temperature Raft Polymerization,” Macromolecules 39 (2006): 1724–1730.

[36] C. Liu, T. Qiu, L. Feng, and Y. Chen, “Synthesis of Temperature-Sensitive Ion-Imprinted Polymer Based on Chitosan for Selective Separation of La3+ From Aqueous Solution: Effect of Different Salt Anions in the Template,” Journal of Environmental Chemical Engineering 11 (2023): 111581.

[37] M. Tsuchiya, Y. Kurashina, and H. Onoe, “Eye-Recognizable and Repeatable Biochemical Flexible Sensors Using Low Angle-Dependent Photonic Colloidal Crystal Hydrogel Microbeads,” Scientific Reports 9 (2019): 17059.

[38] X. Zhao, Y. Liu, C. Shao, et al., “Photoresponsive Delivery Microcarriers for Tissue Defects Repair,” Advanced Science 9 (2022): 2202182.

[39] L. Chen, X. Dai, W. Feng, and Y. Chen, “Biomedical Applications of MXenes: From Nanomedicine to Biomaterials,” Accounts of Materials Research 3 (2022): 785–798.

[40] D. Xu, Z. Li, L. Li, and J. Wang, “Insights Into the Photothermal Conversion of 2D MXene Nanomaterials: Synthesis, Mechanism, and Applications,” Advanced Functional Materials 30 (2020): 2000712.

[41] S. Hao, H. Han, Z. Yang, et al., “Recent Advancements on Photothermal Conversion and Antibacterial Applications over MXenes-Based Materials,” Nano-Micro Letters 14 (2022): 178.

[42] A. H. Mallah, M. Amr, A. Gozen, J. Mendenhall, B. J. Van-Wie, and N. I. Abu-Lail, “Interleukin 1β and Lipopolysaccharides Induction Dictate Chondrocyte Morphological Properties and Reduce Cellular Roughness and Adhesion Energy Comparatively,” Biointerphases 17 (2022): 051001.

[43] C. Lian, T. Tao, P. Su, et al., “Targeting miR-18a Sensitizes Chondrocytes to Anticytokine Therapy to Prevent Osteoarthritis Progression,” Cell Death & Disease 11 (2020): 947.

[44] J. Xie, N. Fu, L. Cai, et al., “The Effects of Interleukin-1β in Modulating Osteoclast-Conditioned Medium’s Influence on Gelatinases in Chondrocytes Through Mitogen-Activated Protein Kinases,” International Journal of Oral Science 7 (2015): 220–231.

[45] H. Hoshi, R. Akagi, S. Yamaguchi, et al., “Effect of Inhibiting MMP13 and ADAMTS5 by Intra-Aarticular Injection of Small Interfering RNA in a Surgically Induced Osteoarthritis Model of Mice,” Cell and Tissue Research 368 (2017): 379–387.

[46] E. Curtis, N. Fuggle, S. Shaw, et al., “Safety of Cyclooxygenase-2 Inhibitors in Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis,” Drugs & Aging 36 (2019): S25–S44.

[47] P. Wojdasiewicz, Ł.A. Poniatowski, and D. Szukiewicz, “The Role of Inflammatory and Anti-inflammatory Cytokines in the Pathogenesis of Osteoarthritis,” Mediators of Inflammation 2014 (2014): 561459.

[48] H. Fang, L. Huang, I. Welch, et al., “Early Changes of Articular Cartilage and Subchondral Bone in the Dmm Mouse Model of Osteoarthritis,” Scientific Reports 8 (2018): 2855.

[49] S. S. Glasson, T. J. Blanchet, and E. A. Morris, “The Surgical Destabilization of the Medial Meniscus (DMM) Model of Osteoarthritis in the 129/SvEv Mouse,” Osteoarthritis and Cartilage 15 (2007): 1061–1069.

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2025 The Author(s). Smart Medicine published by Wiley-VCH GmbH on behalf of Wenzhou Institute, University of Chinese Academy of Sciences.