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

具有免疫调节特性的外泌体功能化聚醚醚酮基植入物,用于增强骨整合

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作者:Lei Fan, Pengfei Guan, Cairong Xiao, Huiquan Wen, Qiyou Wang, Can Liu, Yian Luo, Limin Ma, Guoxin Tan, Peng Yu, Lei Zhou, Chengyun Ning

Abstract

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-κB 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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