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

Abstract

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.

Strategies to Convert Cells into Hyaline Cartilage: Magic Spells for Adult Stem Cells

“…A recent study showed that tetrahedral frame nucleic acids (tFNAs), a novel DNA nanophase material, promoted the chondrogenic differentiation of SM-MSCs through Smad2/3 phosphorylation in vitro [ 112 ], which affected SM-MSC proliferation by activating the Wnt/β-catenin pathway and enhanced the migration activity of SM-MSCs in vitro [ 112 ]. Intra-articular injection of tFNAs in rabbits promoted more rapid cartilage defect regeneration with less fibrous tissue than in the control group after 12 weeks.…”

“…Intra-articular injection of tFNAs in rabbits promoted more rapid cartilage defect regeneration with less fibrous tissue than in the control group after 12 weeks. Such outcomes suggest that tissue restoration was provided by the impact of tFNAs on the number of BM-MSCs that migrated to the defect area [ 112 ].…”

Hydrogel composite scaffolds achieve recruitment and chondrogenesis in cartilage tissue engineering applications

“…After constructing the optimized combination of hydrogels, it is necessary to further modify the homing ability of mesenchymal stem cells to the articular cavity by incorporating biochemical signals that recruit stem cells [23]. In this study, we modified the ECM with the verified bone marrow homing peptide PFS for the first time and added PFS-ECM particles to the GelMA hydrogel to construct a tissue-engineered hydrogel scaffold with a specific MSC recruitment function to promote the homing of MSCs in vivo and in vitro (Fig.…”

“…To assess the viability of BMSCs in different hydrogels, a Live/Dead Assay Kit was used. Cell Counting Kit-8 was used to quantify the proliferation of BMSCs in different hydrogels [23]. The morphology of BMSCs in GelMA, GelMA/ECM and GelMA/ECM-PFS hydrogels was assessed using DAPI staining and FITC-phalloidin staining after 1 d and 7 d of culture, according to the manufacturer's instructions.…”

Advanced injectable hydrogels for cartilage tissue engineering

“…MSCs could differentiate into chondrocytes, osteoblasts, muscle cells, and adipose cells, providing great potential for cartilage tissue engineering. They can be collected from tissues such as bone marrow, umbilical cord blood, adipose, amniotic fluid, pulp, synovium, and even breast milk ( Deng et al, 2014 ; Shao et al, 2015 ; Mohamed-Ahmed et al, 2018 ; Fu et al, 2022 ). MSCs also have immune-enhancing and immunosuppressive effects on the deficiency of primary histocompatibility class II antigens and the secretion of helper T cell type 2 cytokines ( Ding et al, 2021 ).…”