Tetrahedral framework nucleic acids enhance the chondrogenic potential of human umbilical cord mesenchymal stem cells via the PI3K/AKT axis

The field of regenerative medicine faces a notable challenge in terms of the regeneration of articular cartilage.Without proper treatment,it can lead to osteoarthritis.Based on the research findings,human umbilical cord mesenchymal stem cells(hUMSCs)are considered an excellent choice for regenerating cartilage.However,there is still a lack of suitable biomaterials to control their ability to self-renew and differentiate.To address this issue,in this study using tetrahedral framework nucleic acids(tFNAs)as a new method in an in vitro culture setting to manage the behaviour of hUMSCs was proposed.Then,the influence of tFNAs on hUMSC proliferation,migration and chondrogenic differentiation was explored by combining bioinformatics methods.In addition,a variety of molecular biology techniques have been used to investigate deep molecular mechanisms.Relevant results demonstrated that tFNAs can affect the transcriptome and multiple signalling pathways of hUMSCs,among which the PI3K/Akt pathway is significantly activated.Furthermore,tFNAs can regulate the expression levels of multiple proteins(GSK3β,RhoA and mTOR)downstream of the PI3K-Akt axis to further enhance cell proliferation,migration and hUMSC chondrogenic differentiation.tFNAs provide new insight into enhancing the chondrogenic potential of hUMSCs,which exhibits promising potential for future utilization within the domains of AC regeneration and clinical treatment.

Tetrahedral framework nucleic acids promote the biological functions and related mechanism of synovium-derived mesenchymal stem cells and show improved articular cartilage regeneration activity in situ

Many recent studies have shown that joint-resident mesenchymal stem cells(MSCs)play a vital role in articular cartilage(AC)in situ regeneration.Specifically,synovium-derived MSCs(SMSCs),which have strong chondrogenic differentiation potential,may be the main driver of cartilage repair.However,both the insufficient number of MSCs and the lack of an ideal regenerative microenvironment in the defect area will seriously affect the regeneration of AC.Tetrahedral framework nucleic acids(tFNAs),notable novel nanomaterials,are considered prospective biological regulators in biomedical engineering.Here,we aimed to explore whether tFNAs have positive effects on AC in situ regeneration and to investigate the related mechanism.The results of in vitro experiments showed that the proliferation and migration of SMSCs were significantly enhanced by tFNAs.In addition,tFNAs,which were added to chondrogenic induction medium,were shown to promote the chondrogenic capacity of SMSCs by increasing the phosphorylation of Smad2/3.In animal models,the injection of tFNAs improved the therapeutic outcome of cartilage defects compared with that of the control treatments without tFNAs.In conclusion,this is the first report to demonstrate that tFNAs can promote the chondrogenic differentiation of SMSCs in vitro and enhance AC regeneration in vivo,indicating that tFNAs may become a promising therapeutic for AC regeneration.