Programmable DNA hydrogel provides suitable microenvironment for enhancing autophagy-based therapies in intervertebral disc degeneration treatment.

The pathogenesis of intervertebral disc degeneration (IVDD) is attributed to metabolic dysregulation within the extracellular matrix and heightened apoptosis of nucleus pulposus cells (NPC). Therefore, a potential therapeutic strategy for managing IVDD involves the reestablishment of metabolic equilibrium within the extracellular matrix and the suppression of excessive myeloid cell apoptosis. The microRNA, miR-5590, displays marked differential expression in degenerative nucleus pulposus (NP) tissues and exerts a direct influence on the regulation of DDX5 expression. This, in turn, modulates mammalian target of rapamycin (mTOR) phosphorylation, thereby impacting autophagy and apoptosis. However, ensuring the smooth delivery of miRNA to a specific injury site poses a significant challenge. To address this issue, a multifunctional DNA hydrogel was developed and subsequently loaded with miR-5590 via spherical nucleic acids (SNAs) for the treatment of IVDD. The hydrogel, which exhibits versatility, has the potential to be administered through injection at the site of injury, resulting in a consistent and prolonged release of miR-5590. This leads to the creation of a genetic microenvironment within the NP, which triggers the onset of autophagy in NPCs and subsequently suppresses apoptosis. As a result, this process regulates the metabolic equilibrium within the extracellular matrix, thereby impeding the in vitro and in vivo progression of IVDD. The amalgamation of miRNAs and biomaterials offers a promising therapeutic strategy for the management of IVDD in clinical settings.

Biomechanical Effects of Different Single-Level Anterior Cervical Discectomy and Fusion Systems on the Adjacent Segments / 医用生物力学

Objective To compare biomechanical effects of Zero-Profile anterior cervical intervertebral fusion system and Cage-Plate fusion system on the adjacent segments, so as to provide references for the long-term clinical efficacy of single segment cervical spondylosis. Methods The finite element model of cervical spine C1-7 was established based on CT scan data of normal people. After the validity of the model was validated, two finite element models of C5-6 segment implanted with Zero-P fusion system and Cage-Plate fusion system were built. The physiological torque 1.5 N·m was loaded respectively on the normal model, Zero-P implanted model and Cage-Plate implanted model to simulate cervical flexion, extension, lateral bending and rotation. Changes in the ranges of motion (ROMs) of adjacent segments and stresses on nucleus pulposus, endplate and annulus, facet joints of intervertebral disc were compared for the three models. Results After the two kinds of anterior cervical intervertebral fusion systems were implanted, ROMs of C4-5 segments increased by 20%, but ROMs of C6-7 segments increased up to 120%. The stresses on C4-5 nucleus increased by 78%, while the stresses on C6-7 nucleus increased up to 110%. The stresses on the adjacent endplates and the fiber ring also increased. Conclusions The implantation of Cage-Plate and Zero-P fusion system both increased the ROMs of the adjacent segments, and the stresses on annulus, fiber rings and facet joints of the adjacent discs increased as well, which would cause lesions of the adjacent segments in the long run. However, there was no essential difference in biomechanical effects of the Cage-Plate and Zero-P cage fusion system on the adjacent segments.