Tetrahedral DNA nanostructures (TDNs) are a new type of nanomaterials that have recently attracted attention in the field of biomedicine. However, the practical application of nanomaterials is often limited owing to the host immune response. Here, the response of RAW264.7 macrophages to TDNs was comprehensively evaluated. The results showed that TDNs had no observable cytotoxicity and could induce polarization of RAW264.7 cells to the M1 type. TDNs attenuated the expression of NO IL-1β (interleukin-1β), IL-6 (interleukin-6), and TNF-α (tumor necrosis factor-α) in LPS-induced RAW264.7 cells by inhibiting MAPK phosphorylation. In addition, TDNs inhibited LPS-induced reactive oxygen species (ROS) production and cell apoptosis by up-regulating the mRNA expression of antioxidative enzyme heme oxygenase-1 (HO-1). The findings of this study demonstrated that TDNs have great potential as a novel theranostic agent because of their anti-inflammatory and antioxidant activities, high bioavailability, and ease of targeting.
Strategies for functionalizing diverse tetrahedral framework nucleic acids (tFNAs) have been extensively explored since the first successful fabrication of tFNA by Turberfield. One‐pot annealing of at least four DNA single strands is the most common method to prepare tFNA, as it optimizes the cost, yield, and speed of assembly. Herein, the focus is on four key merits of tFNAs and their potential for biomedical applications. The natural ability of tFNA to scavenge reactive oxygen species, along with remarkable enhancement in cellular endocytosis and tissue permeability based on its appropriate size and geometry, promotes cell–material interactions to direct or probe cell behavior, especially to treat inflammatory and degenerative diseases. Moreover, the structural programmability of tFNA enables the development of static tFNA‐based nanomaterials via engineering of functional oligonucleotides or therapeutic molecules, and dynamic tFNAs via attachment of stimuli‐responsive DNA apparatuses, leading to potential applications in targeted therapies, tissue regeneration, antitumor strategies, and antibacterial treatment. Although there are impressive performance and significant progress, the challenges and prospects of functionalizing tFNA‐based nanostructures are still indicated in this review.
Cartilage tissue engineering based on biomimetic scaffolds has become a rapidly developing strategy for repairing cartilage defects. In this study, a biphasic CAN-PAC hydrogel for osteochondral defect (OCD) regeneration was fabricated based on the density difference between the two layers via a thermally reactive, rapid cross-linking method. The upper hydrogel was cross-linked by CSMA and NIPAm, and the lower hydrogel was composed of PECDA, AAm and PEGDA. The interface between the two layers was first grafted by the physical cross-linking of calcium gluconate and alginate, followed by the chemical cross-linking of the carbon-carbon double bonds in the other components. The pore sizes of the upper and lower hydrogels were ~187.4 and ~112.6 μm, respectively. The moduli of the upper and lower hydrogels were ~0.065 and ~0.261 MPa. This prepared bilayer hydrogel exhibited the characteristics of mimetic composition, mimetic structure and mimetic stiffness, which provided a microenvironment for sustaining cell attachment and viability. Meanwhile, the biodegradability and biocompatibility of the CAN-PAC hydrogel were examined in vivo. Furthermore, an osteochondral defect model was developed in rabbits, and the bilayer hydrogels were implanted into the defect. The regenerated tissues in the bilayer hydrogel group exhibited new translucent cartilage and repaired subchondral bone, indicating that the hydrogel can enhance the repair of osteochondral defects.
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