4.8 Article

Biomimetic injectable hydrogel microspheres with enhanced lubrication and controllable drug release for the treatment of osteoarthritis

Journal

BIOACTIVE MATERIALS
Volume 6, Issue 10, Pages 3596-3607

Publisher

KEAI PUBLISHING LTD
DOI: 10.1016/j.bioactmat.2021.03.022

Keywords

Microfluidics; Hydrogel microspheres; Catecholamine chemistry; Hydration lubrication; Drug delivery

Funding

  1. National Natural Science Foundation of China [52022043, 81930051]
  2. Tsinghua UniversityPeking Union Medical College Hospital Initiative Scientific Research Program [20191080593]
  3. Precision Medicine Foundation, Tsinghua University, China [10001020107]
  4. Shanghai Jiao Tong University Medical and Research Program [ZH2018ZDA04]
  5. Science and Technology Commission of Shanghai Municipality [18ZR1434200, 18140901500, 19440760400]
  6. Research Fund of State Key Laboratory of Tribology, Tsinghua University, China [SKLT2020C11]

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In this study, injectable hydrogel microspheres with enhanced lubrication and controllable drug release for OA treatment were developed by bioinspired by the super-lubrication property of cartilage and catecholamine chemistry of mussel. The tribological test and drug release test showed the enhanced lubrication and sustained drug release of the microspheres. Intra-articular injection of the functionalized microspheres into rat knee joint with an OA model provided significant therapeutic effect against the development of OA.
The occurrence of osteoarthritis (OA) is highly associated with the reduced lubrication property of the joint, where a progressive and irreversible damage of the articular cartilage and consecutive inflammatory response dominate the mechanism. In this study, bioinspired by the super-lubrication property of cartilage and catecholamine chemistry of mussel, we successfully developed injectable hydrogel microspheres with enhanced lubrication and controllable drug release for OA treatment. Particularly, the lubricating microspheres (GelMA@DMA-MPC) were fabricated by dip coating a self-adhesive polymer (DMA-MPC, synthesized by free radical copolymerization) on superficial surface of photo-crosslinked methacrylate gelatin hydrogel microspheres (GelMA, prepared via microfluidic technology), and encapsulated with an anti-inflammatory drug of diclofenac sodium (DS) to achieve the dual-functional performance. The tribological test and drug release test showed the enhanced lubrication and sustained drug release of the GelMA@DMA-MPC microspheres. In addition, the functionalized microspheres were intra-articularly injected into the rat knee joint with an OA model, and the biological tests including qRT-PCR, immunofluorescence staining assay, X-ray radiography and histological staining assay all revealed that the biocompatible microspheres provided significant therapeutic effect against the development of OA. In summary, the injectable hydrogel microspheres developed herein greatly improved lubrication and achieved sustained local drug release, therefore representing a facile and promising technique for the treatment of OA.

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