Polyetheretherketone (PEEK) has been widely investigated for improving its biological inert to enable it to achieve stronger osteogenic capability and to be a promising material in implant fields. The most important mechanism that makes a successful implantation is osteointegration. Surface modification is an appropriate method to maintain the excellent mechanical properties of PEEK and simultaneously endow PEEK certain biological characters. In this work, we attempted to shape the nanotopography of PEEK surface by nitrogen low-temperature plasma and polydopamine coating on the surface as a secondary reaction platform to bond the aminated poly (lactic-co-glycolic acid) (PLGA) microspheres encapsulating the BMP-2 gene for enhancing the biological activity. Scanning electron microscope, atomic force microscopy, X-ray photoelectron spectroscopy and water contact angle (CA) measurements were applied to characterize the surface of modified or untreated PEEK. Surface characterization showed that the modification was successfully performed on PEEK including a rougher and more hydrophilic surface with nanotopographic features. The influence on cell adhesion, proliferation and differentiation was evaluated by culturing of rat bone marrow mesenchymal stem cells on different modified PEEK substrates in vitro. The biological results indicated that the low-temperature plasma treatment and PDA-coating on PEEK significantly promoted cell adhesion and proliferation. And the osteogenic differentiation was effectively improved by BMP-2 gene releasing from PLGA-NH 2 microspheres. The results showed that this novel biological surface modification endowed PEEK with outstanding bioactivity and osteogenic ability, providing a theoretical basis for application in the field of implantation. K E Y W O R D S biomaterial, improved cell adhesion, PLGA-NH 2 microspheres, promoted osteogenic differentiation 1 | INTRODUCTION For repairing bone defects resulting from surgery, trauma, diseases, and congenital malformations, titanium-based alloys have become the Shuang Qin and Zhengkuan Lu contributed equally to this work