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.

Drug-loading ZIF-8 for modification of microporous bone scaffold to promote vascularized bone regeneration

Surface modification of microporous bone scaffolds using nanoparticles has been broadly studied in bone tissue engineering.Aiming at improving vascularized bone regeneration(VBR),zeolitic imidazolate framework-8(ZIF-8)was encapsulated with dimethyloxallyl glycine(DMOG)and the drug-carrying nanoparticles(D@Z)could be uniformly coated onto the surface of the bone scaffold.The osteogenic and angiogenic actions of D@Z are closely correlated with the amount of slowly released DMOG,and in general,exhibited a favorable association.Then,the D7.5@Z group,which showed the greatest capacity to induce in vitro osteogenesis-angiogenesis coupling,was utilized for surface modification of the bone scaffold.Biological processes including phosphate-containing compound metabolic process,cell differentiation,cell proliferation and cell motility might contribute to enhanced ability to induce VBR by the coated scaffold and signaling pathways such as Rap1,Ras,phosphatidylinositol 3-kinase/protein kinase B(PI3K-AKT)and vascular endothelial growth factor(VEGF)signaling pathways participated in these processes.Finally,as depicted by in vitro real time-polymerase chain reaction(RT-PCR),Western blot(WB)and in vivo cranial bone defect model,the microporous scaffold coated with nano-D7.5@Z greatly promoted VBR.To conclude,nano-D@Z has significant promise for practical application in modification of microporous bone scaffolds to enhance VBR,and DMOG loading quantity has a beneficial influence on D@Z to improve osteogenesis-angiogenesis coupling.

Micro or nano:Evaluation of biosafety and biopotency of magnesium metal organic framework-74 with different particle sizes

In recent years,various particulate materials have played important roles in medical applications.However,nano-and micron-sized particles of the same material could exhibit distinct properties due to different particle sizes.This finding provided a simple and effective way to improve the biological applications of particulate materials.Therefore,as a highly promising member,the effect of the particle size change of the magnesium metal organic framework-74(Mg-MOF74)was well worth evaluating.Here we firsth assessed the in vitro and in vivo toxicity of micron/nanoscale Mg-MOF74(m-Mg-MOF74/n-Mg-MOF74)in detail.Our in vitro study revealed that compared to micron-sized subjects,n-Mg-MOF74 provided a wider range of safe concentrations.Furthermore,both micron/nanoscale Mg-MOF74 showed good biocompatibility and allowed all the rats under the treatment to survive through the expected experimental periods,with n-Mg-MOF74 still showing lower cardiotoxicity.These advantages of nanoscale Mg-MOF74might benefit from its sustainable and balanced release of Ma^2+both inside and outside the cells.Based on the biosafety evaluation,advanced bio-functional assessments of m/n-Mg-MOF74 including early osteogenesis and angiogenesis were alsoperformed.Similarly,the suitable dose groups of n-Mg-MOF74 achieved optimal early osteogenic promotion and angiogenic stimulation effects.Overall,our combined data delineated the toxicity and biological behaviors of Ma-MOF74 of different scales,and sugqested nanoscale Mg-MOF74 as a better choice for future applications.This result revealed that particle size reductior might be a viable strategy to improve and expand medical applications of MOFs or other particulate materials.