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.

MOFs and bone: Application of MOFs in bone tissue engineering and bone diseases

Metal-organic frameworks(MOFs), a class of hybrid materials, consist of organic linkers and bridging metal ions or clusters. Their tunable pore sizes, large surface area, good biocompatibility, structural variability in combination with materials and chemicals, and osteogenic effects provide potential approaches for bone tissue engineering and bone diseases. And there are more and more research on MOFs in the field of osteogenesis in recent years. This review presents an overall summary of the application in the bone tissue engineering and bone diseases of MOFs and their composites, starting with the synthesis of MOFs, which discusses the advantages and disadvantages of different syntheses. Then, the biological functions of MOFs are discussed, which are the basics of MOFs applied in the organism. Importantly,mechanisms and abundant applications of MOFs are detailed in the bone tissue engineering and bone diseases. Finally, some prospects of MOFs are discussed, for instance, exploring whether MOFs can be used to treat other bone diseases.

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.

Metal-organic framework-based nanomaterials for biomedical applications

In the past decade,nanoscale metal-organic frameworks(nMOFs)have drawn a great attention due to their high porosity,wide range of pore shapes,tunable frameworks and relatively low toxic.With the development of nanotechnology,many researchers studied the synthesis,characterization,functionalization and biotoxicity of nMOFs,and a more thorough understanding was developed about numerous nMOFs as promising platforms for biomedical applications.This review highlights the up-to-date progress of nMOFs related to their bio-applications such as drug delivery,bioimaging,biosensing and biocatalysis,and the common surface modification methods we re classified into four categories:covalent post-synthetically modification,coordinative post-synthetically modification,noncovalent postsynthetically modification and modification on the external surface.At the same time,the challenges and perspectives of nMOFs were discussed as well.

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.

Bio-safety assessment of carbon quantum dots, N-doped and folic acid modified carbon quantum dots: A systemic comparison

The carbon quantum dots(CQDs)and their functionalized materials are promising in biomedical field because of their unique properties;meanwhile,a growing concern has been raised about the potential toxicity of these modified materials in biosystem.In this study,we synthesized original CQDs and two common functionalized CQDs including N-doped CQDs(NCQDs)and folic acid-modified CQDs(FACQDs),and compared the toxicity and biocompatibility with each other in vitro and in vivo.L929,C6 and normal cell MDCK were selected to detect the adverse reaction of these materials in vitro.No acute toxicity or obvious changes were noted from in vitro cytotoxicity studies with the dose of these CQD materials increasing to a high concentration at 1 mg/mL.Among these materials,the FA-CQDs show a much lower toxicity.Moreover,in vivo toxicity studies were performed on the nude mice for 15 days.The experimental animals in 10 or 15 mg/kg groups were similar with animals treated by phosphate buffer solution(PBS)after 15 days.The results of the multifa rious biochemical parameters also suggest that the functionalized products of CQDs do not influence the biological indicators at feasible concentration.Our findings in vitro and in vivo through toxicity tests demonstrate that CQDs and their modified materials are safe for future biological applications.