Multifunctional Mesoporous Calcium-Aluminosilicate Nanoparticles Enable Heterogeneous Activation of Endogenous
Chun Xu1,2, Qingxuan Chen3, Hang Chen1,2
1Sydney Dental School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales2006, Australia.
Abstract:
The development of multifunctional biomaterials capable of simultaneously activating endogenous growth factors, promoting rapid hemostasis, and enhancing bone regeneration remains a significant challenge in regenerative medicine. Here, we report a rationally designed calcium-aluminosilicate dendritic mesoporous silica nanoparticle (CaAl-DMSN) that integrates heterogeneous catalytic growth factor activation with pro-coagulant and osteogenic functionalities in a single nanoscale platform. Featuring a four-coordinate aluminosilicate framework functionalized with calcium in a radial large-pore architecture, CaAl-DMSN generates a nanoconfined alkaline microenvironment via Ca2+ mediated hydroxide enrichment. This enables more than an order-of-magnitude higher activation efficiency of latent Transforming Growth Factor β1 (TGF-β1) compared to conventional homogeneous alkaline catalysis. Molecular dynamics simulations reveal a markedly reduced free-energy barrier for TGF-β1 dissociation, establishing a direct structure-function relationship between composition, nanostructure, and catalytic activity. Functionally, CaAl-DMSN induces rapid clot formation, enhances CD105+ CD73+ mesenchymal stromal cell recruitment, and promotes osteogenic differentiation via Smad signaling activation. In a rat critical-size calvarial defect model, CaAl-DMSN increases bone volume fraction by ∼80% compared with controls, while exhibiting excellent biocompatibility. Collectively, CaAl-DMSN couples interfacial chemistry, endogenous growth factor activation, hemostasis, and regenerative microenvironment modulation, offering a growth factor-free strategy for bone repair and broader tissue regeneration applications.
