Fabrication of a hierarchically porous PMMA/PEI/ZnO osteogenic scaffold and its bone repair efficacy

Abstract Small-sized bone defects can be repaired by self-healing, but it is difficult for the critical-size bone defect (CSBD). While autologous bone grafting remains the gold standard, its limited availability, however, constrains widespread clinical application. As a promising alternative, artificial bone substitute scaffolds are designed to mimic the extracellular matrix (ECM) microenvironment. In this study, we developed a hierarchically porous polymethyl methacrylate/polyethyleneimine/ZnO scaffold via anti-solvent vapor-induced phase separation, replicating the ECM microenvironment of natural bone. The scaffold exhibited: (1) structural & mechanical properties: a cancellous bone-like porous structure with endogenous stress. (2) In vitro , the scaffolds demonstrated excellent biocompatibility, effectively supporting the adhesion, proliferation, and osteogenic differentiation of rat bone marrow mesenchymal stem cells. (3) In vivo , this performance consequently translated into enhanced repair of CSBDs in animal models. This scaffold provides a novel approach for bone tissue engineering, combining structural mimicry, bioactivity, and mechanical strength for effective bone regeneration.