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

ABSTRACT

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.