Background: Injectable and self-setting bone substitutes hold significant value for minimally invasive repair of bone defects. However, these materials typically possess a dense structure, which conflicts with the porous architecture required for cell infiltration and bone regeneration. Conventional porogen strategies (e.g., porogen leaching and gas foaming) often compromise injectability or result in isolated pores, leading to suboptimal repair outcomes.
Methods: Using calcium polyphosphate (Ca-polyP) coacervate as the injectable matrix, we introduced MgP–gelatin core–shell powders (MgP:gelatin = 5:1) as functional porogens. The core–shell structure comprises a gelatin core coated with an alkaline MgP shell. Upon mixing with the acidic Ca-polyP coacervate, the MgP shell triggers an acid-base neutralization reaction that initiates self-setting and activates the setting-induced liquid–solid phase separation (SIPS) mechanism, generating abundant micropores (1–10 μm). Concurrently, the MgP shell serves as a physical barrier to delay water penetration into the gelatin core, ensuring undisturbed SIPS. After complete setting, gradual dissolution of the gelatin core results in the formation of interconnected macropores (40–60 μm), with optimal porosity achieved at day 5. The setting behavior, pore architecture, and biological functions were systematically evaluated.
Results: Through the MgP–gelatin core–shell design, we successfully fabricated bone repair scaffolds with a hierarchical "microporous wall + macroporous channel" structure. In vitro, the composite significantly promoted BMSC osteogenic differentiation, as evidenced by markedly elevated expressions of iBSP, OCN, and osterix. In vivo, the hierarchical porosity effectively guided host-cell infiltration and new bone formation; at 8 weeks post-implantation, bone volume fraction (BV/TV) and trabecular thickness (Tb.Th) were 1.37-fold and 1.23-fold higher than those of the blank control group, respectively, indicating enhanced repair of rat femoral defects.
Conclusion: By introducing MgP–gelatin core–shell porogens, this study resolves the critical challenge of achieving interconnected macropores in injectable self-setting materials. This strategy offers a versatile platform for designing bone repair materials that combine injectability, self-setting capability, and ideal porous architecture.
