Aspirin/PLGA coated 3D-printed Ti-6Al-4V alloy modulate macrophage polarization to enhance osteoblast differentiation and osseointegration

Abstract

Although titanium (Ti) and Ti-based alloy have been widely used as dental and orthopedic implant materials, its bioinertness hindered the rapid osseointegration. Therefore, it is recommended to acquire ideal topographic and chemical characteristics through surface modification methods. 3D printing is a delicate manufacture technique which possesses superior controllability and reproducibility. While aspirin serve as a well-established non-steroidal anti-inflammatory agent. Recently, the importance of immune system in regulating bone dynamics has attracted increasing attention. We herein superimposed the aspirin/poly (lactic–co–glycolic acid) (ASP/PLGA) coating on the 3D-printed Ti-6Al-4V surface with uniform micro-structure to establish the Ti64-M-ASP/PLGA substrate. Scanning electron microscopy (SEM), x-ray photoelectron spectroscopy (XPS) and contact angle test confirmed the successful fabrication of the Ti64-M-ASP/PLGA substrate, with increased wettability and sustained release pattern of ASP. Compared with the Ti64 base material, the Ti64-M-ASP/PLGA substrate showed enhanced M2 and depressed M1 genes and proteins expressions in macrophages. The novel Ti64-M-ASP/PLGA substrate also displayed enhanced osteoblast proliferation, adhesion, extracellular mineralization ability and osteogenic gene expressions when cultured with macrophage conditioned medium in vitro. Furthermore, rat femora implantation model was used for in vivo evaluation. After 4 weeks of implantation, push out test, micro-computed tomography (micro-CT) and histological analyses all confirmed the superior osseointegration capabilities of the Ti64-M-ASP/PLGA implant than the other groups. Our study revealed the synergistic role played by 3D-printed micro topography and immunoregulatory drug aspirin in promoting osteogenesis in vitro and accelerating osseointegration in vivo, thus providing a promising method for better modifying the implant surface.Graphical abstract