Fan Lei, Guan Pengfei, Xiao Cairong, Wen Huiquan, Wang Qiyou, Liu Can, Luo Yian, Ma Limin, Tan Guoxin, Yu Peng, Zhou Lei, Ning Chengyun
School of Materials Science and Engineering & National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, 510641, China.
Department of Orthopedic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Bioact Mater. 2021 Feb 15;6(9):2754-2766. doi: 10.1016/j.bioactmat.2021.02.005. eCollection 2021 Sep.
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. results showed the Exos loaded SPEEK promoted macrophage M2 polarization via the NF-κB pathway to enhance BMSCs osteogenic differentiation. Further 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.
宿主免疫系统对生物材料的反应对于确定植入物的命运和骨再生特性至关重要。骨髓干细胞（BMSCs）衍生的外泌体（Exos）含有多种生物信号分子，并已被证明具有免疫调节功能。在此，我们开发了一种BMSC衍生的Exos功能化植入物，通过免疫调节来加速骨整合。通过单宁酸（TA）与生物大分子的强相互作用，BMSC衍生的Exos可逆地结合在TA修饰的磺化聚醚醚酮（SPEEK）上。从SPEEK缓慢释放的Exos可被共培养细胞吞噬，这可以有效提高SPEEK的生物相容性。结果表明，负载Exos的SPEEK通过NF-κB途径促进巨噬细胞M2极化，以增强BMSCs的成骨分化。进一步通过大鼠气袋模型和大鼠股骨钻孔模型评估负载Exos的SPEEK，发现其具有有效的巨噬细胞M2极化、理想的新骨形成和令人满意的骨整合。因此，BMSC衍生的Exos功能化植入物发挥了骨免疫调节作用以促进骨生成。
