Magnesium oxide nanoparticles modulate phase separation to form trabecular-structured cryogels for bone defect repair
Botao Liu, Mingming Hao, Jianping Chen, Xiaodong Hu, Jiaqi Zhong, Yujiong Chen, Yu Han, Hangbin Weng, Zhewei Zhang, Tianyu Du, Zhaoxiang Peng
Abstract
Critical-sized bone defects pose notable therapeutic challenges and often require extensive bone grafts for effective intervention, leading to a substantial medical burden. The scarcity of autologous bone and the complex architecture of trabecular bone necessitate the development of cost-effective biomimetic graft materials. In this study, we developed a MgO nanoparticle-incorporated hydrogel scaffold (P-G-C-MgO2) using a freeze-induced phase separation approach. The scaffold achieved a porous structure with 56.48 ± 7.062% porosity and an average pore size of 565.7 ± 53.62 μm, closely mimicking natural trabecular bone. It demonstrated exceptional mechanical stability during degradation and consistently released bioactive components, including Mg 2+ , type I collagen, and gelatin. These features facilitated early cell recruitment and osteogenic differentiation. In a distal femoral bone defect model, P-G-C-MgO2 exhibited excellent osseointegration and significantly enhanced new bone regeneration. This biomimetic design offers a promising solution for bone defect repair. Moreover, it established a novel phase-separation-based strategy for fabricating porous hydrogel scaffolds. Magnesium oxide nanoparticles modulate the phase separation of gelatin, type I collagen, and PVA during the freezing process, creating a biomimetic trabecular porous hydrogel structure. As the hydrogel degrades, it releases magnesium ions and bioactive components, which effectively recruit stem cells to the defect site. The cells colonize the porous matrix and are then induced to differentiate osteogenically, achieving efficient repair of bone defects.