Department of Materials Science and Engineering Southern University of Science and Technology, Shenzhen, Guangdong 518055, China.
Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Room 3069, Viikinkaari 5E, 00790 Helsinki, Finland.
ACS Biomater Sci Eng. 2024 Oct 14;10(10):6120-6134. doi: 10.1021/acsbiomaterials.4c00725. Epub 2024 Sep 18.
The repair of critical-sized bone defects remains a major challenge for clinical orthopedic surgery. Here, we develop a surface biofunctionalized three-dimensional (3D) porous polyether-ether-ketone (PEEK) scaffold that can simultaneously promote osteogenesis and regulate macrophage polarization. The scaffold is created using polydopamine (PDA)-assisted immobilization of silk fibroin (SF) and the electrostatic self-assembly of nanocrystalline hydroxyapatite (nano-HA) on a 3D-printed porous PEEK scaffold. The SF/nano-HA functionalized surface provides a bone-like microenvironment for osteoblastic cells' adhesion, proliferation, mineralization and osteogenic differentiation. Moreover, the biofunctionalized surface can effectively drive macrophages polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. Integrin β1-specific cell-matrix binding and the activation of Ca receptor-mediated signaling pathway play critical roles in the regulation of macrophage polarization. Compared with the as-printed scaffold, the SF/nano-HA functionalized porous PEEK scaffold induces minimal inflammatory response, enhanced angiogenesis, and substantial new bone formation, resulting in improved osseointegration . This study not only develops a promising candidate for bone repair but also demonstrates a facile surface biofunctionalization strategy for orthopedic implants to improve osseointegration by stimulating osteogenesis and regulating immunity.
治疗临界尺寸骨缺损仍然是临床骨科手术的主要挑战。在这里,我们开发了一种表面生物功能化的三维(3D)多孔聚醚醚酮(PEEK)支架,它可以同时促进成骨和调节巨噬细胞极化。该支架是通过聚多巴胺(PDA)辅助固定丝素蛋白(SF)和纳米晶羟基磷灰石(nano-HA)在 3D 打印多孔 PEEK 支架上的静电自组装来制备的。SF/nano-HA 功能化表面为成骨细胞的黏附、增殖、矿化和成骨分化提供了类似于骨的微环境。此外,生物功能化表面可以有效地将巨噬细胞从促炎 M1 表型极化为抗炎 M2 表型。整合素 β1 特异性细胞基质结合和钙受体介导的信号通路的激活在调节巨噬细胞极化中起着关键作用。与打印支架相比,SF/nano-HA 功能化多孔 PEEK 支架引起的炎症反应最小,血管生成增强,大量新骨形成,从而改善了骨整合。这项研究不仅开发了一种有前途的骨修复候选物,而且还展示了一种用于骨科植入物的简便表面生物功能化策略,通过刺激成骨和调节免疫来改善骨整合。