• The preparation of a porous interpenetrating polymer network (IPN) scaffold by salt leaching, featuring large pore sizes and excellent biological activity. • Collagen incorporation not only increased the strength of the scaffold but also improved its early cell adhesion. • Salt-leached scaffolds demonstrate superior angiogenic and bone regenerative capabilities. • Salt-leached scaffolds promote the osteogenic differentiation of cells by activating the PI3K/AKT pathway, thereby facilitating bone regeneration. To address the issue of unsatisfactory repair outcomes in large bone defects due to insufficient vascularization in bone tissue engineering. In this study, a porous interpenetrating polymer network (IPN) scaffold featuring large pore sizes and excellent biological activity was constructed through salt leaching and collagen incorporation. Collagen incorporation not only increased the strength of the scaffold and regulated its physical properties, such as the swelling rate, degradation rate, and porosity but also improved its biological properties, such as early cell adhesion. By screening the particle size of the salt porogen, IPN scaffolds with various pore sizes were obtained by leaching after gelation. The scaffold with a pore size 150–255 μm demonstrated optimal performance, promoting rBMSC proliferation and osteogenic differentiation in vitro, with in vivo experiments confirming its superior angiogenic and bone regenerative capabilities. RNA sequencing indicated that the scaffolds promoted osteogenic differentiation of cells by activating the PI3K/AKT pathway, thereby facilitating bone regeneration. In summary, the porous IPN scaffolds developed in this study can significantly enhance angiogenesis and bone regeneration, suggesting promising prospects for advancing bone tissue engineering from laboratory research to clinical application.
Tian et al. (2026) studied this question.