Synthesis and potential osteogenic applications of Wnt3a‐loaded ZIF‐8 nanoparticles

The Wnt signaling pathway plays a critical role in bone homeostasis, and the related protein therapy strategies have been reported to have great potential in osseointegration; however, they face formidable challenges such as complex external environments and unavoidable protein denaturation. In this work, we report a novel approach combining the synthesis of metal–organic frameworks (MOFs) and protein encapsulation in a one-pot process based on zeolitic imidazolate framework-8 (ZIF-8) and Wnt3a protein, with improved biomechanical behavior and enhanced protein biological response. This combination was designed to enhance the Wnt3a protein function through the improved chemical stability provided by the ZIF-8 crystals. Additionally, the zinc ions contained in the ZIF-8 crystals induced bone homeostasis, further favoring the osteogenesis. The results showed that the Wnt3a protein-loaded ZIF-8 crystals served as efficient drug delivery vehicles to promote osteogenesis, preventing protein denaturation. In particular, Wnt3a-loaded ZIF-8 nanoparticles (Wnt3a@ZIF-8 NPs) had higher efficacy on bone marrow mesenchymal stem cells (BMSCs) than ZIF-8 NPs or Wnt3a proteins, contributing to the osteogenesis through ZIF-8 crystals and intracellular Wnt3a proteins released from Wnt3a@ZIF-8 NPs. Furthermore, polymerase chain reaction (PCR) analysis showed that the osteogenic pathways were upregulated. Overall, the present one-pot process can open up new avenues to develop signaling protein-delivery systems for applications in protein therapy strategies.