Osteoarthritis (OA) is a musculoskeletal disorder disease affecting about 500 million people worldwide and mesenchymal sem cells (MSCs) therapy has been demonstrated as a potential strategy to treat OA. However, the shear forces during direct injection and the harsher shear condition of OA environments would lead to significant cell damage and inhibit the therapeutic efficacy. Herein, DNA supramolecular hydrogel has been applied as delivering material for MSCs to treat severe OA model, which perform extraordinary protection in MSCs against the shear force both in vitro and in vivo. It is demonstrated that the DNA supramolecular hydrogel can promote formation of quality cartilage, reduce osteophyte, and normalize subchondral bone under the high friction condition of OA, whose molecular mechanisms underlying therapeutic effects are also investigated. It can be anticipated that DNA supramolecular hydrogel would be a promising cell delivery system for multiple potential MSCs therapy.

A novel supramolecular DNA hydrogel system was designed based on a directly synthesized chemically branched DNA. For the hydrogel formation, a self-dimer DNA with two sticky ends was designed as the linker to induce the gelation of B-Y. By programing the linker sequence, thermal and metal-ion responsiveness could be introduced into this hydrogel system. This supramolecular DNA hydrogel shows shear-thinning, designable responsiveness, and good biocompatibility, which will simplify the hydrogel composition and preparation process of the supramolecular DNA hydrogel and accelerate its biomedical applications.

DNA hydrogels have attracted increasing attention owing to their excellent permeability and high mechanical strength, together with thixotropy, versatile programmability and good biocompatibility. However, the moderate biostability and immune stimulation of DNA have arisen as big concerns for future potential clinical applications. Herein, we report the self-assembly of a novel L-DNA hydrogel, which inherited the extraordinary physical properties of a D-DNA hydrogel. With the mirror-isomer deoxyribose, this hydrogel exhibited improved biostability, withstanding fetal bovine serum (FBS) for at least 1 month without evident decay of its mechanical properties. The low inflammatory response of the L-DNA hydrogel has been verified both in vitro and in vivo. Hence, this L-DNA hydrogel with outstanding biostability and biocompatibility can be anticipated to serve as an ideal 3D cell-culture matrix and implanted bio-scaffold for long-term biomedical applications.Hydrogels possess similar molecular networks and exhibit comparable physical properties to the natural extracellular matrix (ECM), and have therefore provided an ideal platform for three-dimensional (3D) cell culture and tissue engineering. [1] Among them, DNA hydrogels have attracted much attention owing to their unique properties, including excellent permeability and high mechanical strength, together with thixotropy, versatile programmability and good biocompatibility, [2] which have promoted their application in cell manipulation, [3] targeted therapy, [4] 3D bio-printing, [5] drug delivery, [6] and tissue regeneration. [7] In previous studies, DNA hydrogels have been demonstrated with good cytocompatibility in vitro. However, some concerns on their inflammation in vivo arose recently, because some DNA components and their degradation fragments are reported to lead to the stimulation of immune responses, [8] for example, CpG as a vaccine adjuvant. [9] While many efforts have been made to decrease the immune responses [8b, 10] of DNA materials, quick hydrolysis of DNA under physiological conditions is still another challenge for their long-term application. [11] Therefore, there is an urgent need to reduce

A DNA building block with tunable rigidity was constructed, and the corresponding hydrogel formation process was investigated accordingly. A high rigidity was demonstrated to facilitate fast gelation. Different gelation pathways of the rigid and flexible building blocks were revealed, and a cyclized dimer intermediate was proposed. The energy barrier of the ring-opening process was also shown to play a fundamental role in determining the gelation kinetics. Furthermore, the hydrogel molecular network rigidity was also tuned in situ through strand displacement, which also supports the kinetic control mechanism of the formation process of DNA hydrogels.

DNA hydrogels have attracted increasing attention owing to their excellent permeability and high mechanical strength, together with thixotropy, versatile programmability and good biocompatibility. However, the moderate biostability and immune stimulation of DNA have arisen as big concerns for future potential clinical applications. Herein, we report the self‐assembly of a novel l‐DNA hydrogel, which inherited the extraordinary physical properties of a d‐DNA hydrogel. With the mirror‐isomer deoxyribose, this hydrogel exhibited improved biostability, withstanding fetal bovine serum (FBS) for at least 1 month without evident decay of its mechanical properties. The low inflammatory response of the l‐DNA hydrogel has been verified both in vitro and in vivo. Hence, this l‐DNA hydrogel with outstanding biostability and biocompatibility can be anticipated to serve as an ideal 3D cell‐culture matrix and implanted bio‐scaffold for long‐term biomedical applications.