Dual-dynamic-bond cross-linked injectable hydrogel of multifunction for intervertebral disc degeneration therapy

Abstract

Developing smart hydrogels with integrated and suitable properties to treat intervertebral disc degeneration (IVDD) by minimally invasive injection is of high desire in clinical application and still an ongoing challenge. In this work, an extraordinary injectable hydrogel PBNPs@OBG (Prussian blue nanoparticles@oxidized hyaluronic acid/borax/gelatin) with promising antibacterial, antioxidation, rapid gelation, and self-healing characteristics was designed via dual-dynamic-bond cross-linking among the oxidized hyaluronic acid (OHA), borax, and gelatin. The mechanical performance of the hydrogel was studied by dynamic mechanical analysis. Meanwhile, the swelling ratio and degradation level of the hydrogel was explored. Benefiting from its remarkable mechanical properties, sufficient tissue adhesiveness, and ideal shape-adaptability, the injectable PBNPs containing hydrogel was explored for IVDD therapy. Astoundingly, the as-fabricated hydrogel was able to alleviate H2O2-induced excessive ROS against oxidative stress trauma of nucleus pulposus, which was further revealed by theoretical calculations. Rat IVDD model was next established to estimate therapeutic effect of this PBNPs@OBG hydrogel for IVDD treatment in vivo. On the whole, combination of the smart multifunctional hydrogel and nanotechnology-mediated antioxidant therapy can serve as a fire-new general type of therapeutic strategy for IVDD and other oxidative stress-related diseases.

Oxidative stress in intervertebral disc degeneration: Molecular mechanisms, pathogenesis and treatment

“…In terms of regulating ECM metabolism, PBNPs maintained ECM quality by down‐regulating the expression of MMP‐3, 9, 13 and ADAMTS‐5 and up‐regulating the expression of Col II a1 and Agg 255 . Recently, Yang et al 256 designed a special injectable hydrogel PBNPs@OBG by double dynamic bond cross‐linking between oxidized hyaluronic acid (OHA), borax and gelatin. PBNPs@OBG has the properties of injectability, repeatability, self‐healing, adhesion, antibacterial and long‐term retention, which can provide stable and sustainable release of PBNPs.…”

Isoginkgetin-loaded reactive oxygen species scavenging nanoparticles ameliorate intervertebral disc degeneration via enhancing autophagy in nucleus pulposus cells

“…However, traditional therapeutic agents have difficulty accessing the interior of avascular intervertebral discs, so they can only reduce inflammation and temporarily relieve pain outside the intervertebral disc but cannot remove accumulated ROS, which makes them unable to fundamentally prevent the progression of IDD [ 31 , 32 ]. Although some studies have used novel biomaterials to deliver drugs into the intervertebral disc and effectively reduce ROS levels, oxidatively damaged organelles are not removed simultaneously, which may cause blockage in the repair of cell viability and metabolic function, ultimately affecting the therapeutic effect [ 14 , 33 , 34 ]. Therefore, there is an urgent need to develop new strategies to effectively treat IDD by removing damaged organelles and reducing ROS.…”

“…Early recognition and removal of excessive ROS is a viable therapeutic strategy [ 12 , 13 ]. For instance, Yang et al [ 14 ] designed an injectable composite hydrogel, which sustained the release of Prussian blue nanoparticles to clear excessive ROS and showed good therapeutic effects in a rat IDD model. Although this strategy can effectively remove excessive ROS, nucleus pulposus cells (NPCs) cannot completely repair oxidative damaged biomolecules and organelles, which seriously affects the metabolic balance and cell viability, and may eventually lead to apoptosis [ 15 , 16 ].…”

Nucleus pulposus cell-derived efficient microcarrier for intervertebral disc tissue engineering

“…One limitation of our NPCMs is that they are microspherical bioscaffolds, which have difficulty mechanically supporting the disc. Hydrogel scaffolds can buffer the pressure applied to IVDs after gelation [64]. Pairing the NPCMs with the proper hydrogel during injection may improve the mechanical properties of our scaffold.…”