Bioactive surface-porous polyetherketoneketone materials (PEKK-BSP) were prepared by first leaching hydroxyapatite (HA) microsphere templates from compression molded PEKK/HA composites (i.e., PEKK-P) followed by sulfonation with 80% sulfuric acid for 3 h (i.e., PEKK-SP) and then soaking in a simulated body fluid (SBF) for 5 days. The combination of both physical and chemical processes created a surface-porous PEKK material (PEKKSP) that had both structurally interconnected and open macropores (200-600 mu m) because of templating of HA microspheres, and micropores (<10 mu m) due to effects of the sulfonation. The in vitro bioactivity of PEKK-SP was demonstrated by the development of a dense layer of bone-like apatite inside and on the surfaces after SBF treatment. The sulfonation process followed SBF treatment also significantly reduced the water contact angle of PEKK material. Mechanical tests showed that both PEKK-BSP and PEKK-P were a little better than PEKK-SP in terms of compressive strength and modulus. In vitro cell culture using rabbits' mesenchymal stem cells (MSCs) demonstrated that PEKK-BSP promoted better cell growth and proliferation than other groups of PEKK materials. Moreover, compared to PEKK material alone, PEKK-BSP elevated gene expressions of osteocalcin (OCN), Type I collagen (Col-I), alkaline phosphatase (ALP), and runt-related transcription factor 2 (Runx2). This bioactive PEKK-BSP material has potential application for spinal interbody fusion devices to enhance their in vivo osseointegration.