Injectable Bone Cements: A Generational Framework for Bioactivity, Porosity, and Mechanobiological Design at the Nanoscale

Abstract

Injectable bone cements (IBCs) are widely used in orthopaedic and craniofacial applications due to their minimally invasive delivery and ability to provide early mechanical stabilisation. Despite substantial progress, clinical translation remains limited by persistent challenges, including insufficient bioactivity, poor control of porosity and interconnectivity, and the limited integration of mechanobiological design principles. Additional constraints arise from the need to balance injectability, setting behaviour, and mechanical performance. Most existing reviews categorise IBCs by material composition, often overlooking important conceptual advances in functionality. Here, we propose a generation-based classification framework that captures successive shifts in injectable cement design, from first-generation bioinert structural fillers to second-generation resorbable, osteoconductive systems, to third-generation bioactivity-enhanced doped and composite formulations, and finally to fourth-generation cements incorporating hierarchical macro- and nanoscale architectures. This latest generation integrates nanomaterials and engineered pore structures to regulate cell–matrix interactions, mechanotransduction, and tissue regeneration. Across each generation, we critically examine the interdependence of biological, mechanical, and rheological properties, highlighting how architectural and mechanical cues modulate cellular responses. By synthesising advances in materials science and mechanobiology, this review outlines emerging strategies for the design of regenerative, mechanobiologically informed IBCs.