Setting‐Induced Dual Pore Formation in Polyphosphate Coacervate Enables Injectable Implants With In Situ Hierarchical Porosity and Tunable Compositions for Bone Regeneration

Injectable and self-setting biomaterials are significantly advantageous in minimally invasive bone repair. However, the in situ (post-injection) fabrication of abundant porous structures permissive for cellular ingrowth-a fundamental requirement for achieving efficient bone regeneration-poses a considerable challenge. Here, this study finds that calcium polyphosphate (Ca-polyP) coacervate, a liquid precursor of osteogenic Ca-polyP solid, enables in situ dual pore-forming individually or simultaneously: setting-induced liquid-solid phase separation (SIPS) and setting-induced gas foaming (SIGF), which can be triggered by different inorganic base substances as setting initiators. Notably, SIPS pioneers the observation of such a process in inorganic self-setting systems. Following this, we develop an array of injectable and self-setting Ca-polyP coacervate-based composites, where the two mechanisms produce distinct pore size ranges in situ, i.e., tens-micrometers via SIPS and hundreds-micrometers via SIGF. Variable setting initiators allow tuning of composition and properties. We further apply a typical composite (IS-polyP) with in situ formed hierarchical pores built upon simultaneous SIPS and SIGF for bone repair. Investigations reveal that IS-polyP can significantly enhance energy metabolism, cell proliferation, and osteogenic differentiation of BMSCs, ultimately promoting bone regeneration and growth of new bone in the macropores. This work establishes a universal design strategy for in situ porous implants in orthopedics.