4.8 Article

Exosome-functionalized polyetheretherketone-based implant with immunomodulatory property for enhancing osseointegration

Journal

BIOACTIVE MATERIALS
Volume 6, Issue 9, Pages 2754-2766

Publisher

KEAI PUBLISHING LTD
DOI: 10.1016/j.bioactmat.2021.02.005

Keywords

Osteoimmunology; Macrophages polarization; Polyetheretherketone; BMSC-Derived exosomes; Bone regeneration

Funding

  1. National Natural Science Foundation of China [51932002, 51903087, 51772106, 31771080]
  2. Natural Science Foundation of Guangdong Province [2020A1515011369]
  3. Science and Technology Program of Guangzhou [202002030308]
  4. Science and Technology Innovation Team Project of Foshan [2018IT100101]
  5. Sino-Singapore International Joint Research Institute [203-A018004]

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A BMSC-derived Exos-functionalized implant was developed to accelerate bone integration through immunoregulation, which improved the biocompatibilities of SPEEK and promoted macrophage polarization, osteogenic differentiation, and new bone formation.
The host immune response effecting on biomaterials is critical to determine implant fates and bone regeneration property. Bone marrow stem cells (BMSCs) derived exosomes (Exos) contain multiple biosignal molecules and have been demonstrated to exhibit immunomodulatory functions. Herein, we develop a BMSC-derived Exos-functionalized implant to accelerate bone integration by immunoregulation. BMSC-derived Exos were reversibly incorporated on tannic acid (TA) modified sulfonated polyetheretherketone (SPEEK) via the strong interaction of TA with biomacromolecules. The slowly released Exos from SPEEK can be phagocytosed by co-cultured cells, which could efficiently improve the biocompatibilities of SPEEK. In vitro results showed the Exos loaded SPEEK promoted macrophage M2 polarization via the NF-kappa B pathway to enhance BMSCs osteogenic differentiation. Further in vivo rat air-pouch model and rat femoral drilling model assessment of Exos loaded SPEEK revealed efficient macrophage M2 polarization, desirable new bone formation, and satisfactory osseointegration. Thus, BMSC-derived Exos-functionalized implant exerted osteoimmunomodulation effect to promote osteogenesis.

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