Bridging the missing middle in osseointegration: meso-scale topography between macro design and microroughness.

PURPOSE: Despite decades of clinical success with microrough implant surfaces, persistent challenges-particularly the biological trade-off between osteoblast proliferation and differentiation-highlight the need for novel surface design strategies. This review investigates the potential of meso-scale topography (10-500 μm) as a promising and underexplored dimension in implant surface engineering, situated between macro-level implant geometry and conventional microroughness. METHODS: A systematic review, supplemented by a targeted literature search, was conducted to evaluate the biological and mechanical roles of meso-scale surface features on titanium, zirconia, and scaffold materials. Studies employing laser texturing, chemical etching, and 3D printing/additive manufacturing were critically assessed. Comparative insights across nano-, micro-, and meso-scale features were synthesized to delineate their distinct and synergistic contributions to osseointegration. RESULTS: Meso-scale features confer unique biological and mechanical advantages not achievable by nano- or micro-scale designs alone. These include enhanced osteoblast recruitment/attachment, spatial organization, extracellular matrix alignment, and mechanical interlocking. Notably, meso-topography appears to resolve the classic proliferation-differentiation dichotomy observed with microrough surfaces. Many meso-scale designs also exhibit increased interfacial surface area, correlating with superior mechanical fixation. Biomimetic meso-patterns-mimicking osteoblast dimensions and native bone microarchitecture-demonstrate contact-guidance effects that promote cell alignment and matrix deposition. Most importantly, titanium and zirconia surfaces with engineered meso-topography consistently improve biological integration and biomechanical anchorage. Yet, these features remain largely absent in current clinical implants due to knowledge gaps, technical constraints, and manufacturing limitations. CONCLUSION: Meso-scale topography offers a powerful yet underutilized strategy to enhance osseointegration. Future implant designs should adopt an integrative, hierarchical approach that combines microroughness with meso-scale structuring to achieve synergistic improvements in cellular behavior, mechanical stability, and early healing. This strategy aligns with the hierarchical organization of natural bone and holds the potential to overcome longstanding biological bottlenecks in implant dentistry. Bridging the gap between biological potential and technological feasibility will be essential to advancing next-generation implant surface design.