Injectable self-healing hydrogel with siRNA delivery property for sustained STING silencing and enhanced therapy of intervertebral disc degeneration

Inflammatory responses of nucleus pulposus(NP)can induce imbalanced anabolism and catabolism of extracellular matrix,and the cytosolic dsDNA accumulation and STING-NF-κB pathway activation found in NP inflammation are considered as fairly important cause of intervertebral disc(IVD)degeneration.Herein,we constructed a siSTING delivery hydrogel of aldehyde hyaluronic acid(HA-CHO)and poly(amidoamine)PAMAM/siRNA complex to intervene the abnormal STING signal for IVD degeneration treatment,where the formation of dynamic Schiff base bonds in the system(siSTING@HPgel)was able to overcome the shortcomings such as low cellular uptake,short half-life,and rapid degradation of siRNA-based strategy.PAMAM not only formed complexes with siRNA to promote siRNA transfection,but also served as dynamic crosslinker to construct hydrogel,and the injectable and self-healing hydrogel efficiently and steadily silenced STING expression in NP cells.Finally,the siSTING@HPgel significantly eased IVD inflammation and slowed IVD degeneration by prolonging STING knockdown in puncture-induced IVD degeneration rat model,revealing that STING pathway was a therapeutic target for IVD degeneration and such novel hydrogel had great potential for being applied to many other diseases for gene delivery.

Optimizing coil configurations for AC loss reduction in REBCO HTS fast-ramping magnets at cryogenic temperatures

AC loss is one of the critical issues for designing REBCO fast‐ramping magnets operating at cryogenic temperatures.There are many ways to reduce AC loss for coil windings.However,it is not clear which method is the most effective way to minimize AC loss in the coil windings for a given Ampere‐turns.In this work,we numerically studied coil configurations of several small superconducting magnets constructed from 12 mm SuperPower REBCO coated conductors,for fast‐ramping application with the same Ampere‐turns to identify the lowest AC loss among them.The HTS magnets have a total turn number of 50 and inner diameter of 30 cm,carrying AC current operating in the temperature range of 20–40 K at 25 Hz.We incorporated several existing loss reduction strategies including spacing between the turns for single pancake coils,grading Ic values for the solenoid configuration,and applying flux diverters to shape the magnetic field around the coil windings.The simulation was implemented using a homogenized H‐formulation.Across all studied loss reduction methods,the use of flux diverters has the largest impact in AC loss reduction.The AC loss values in the solenoid winding comprising a stack of five single pancake coils with 0.1 mm turn‐to‐turn gap with the flux diverters agree well with those in the single pancake coil for 2 mm turn‐to‐turn gap with the flux diverters.Solenoid type coil configurations with flux diverters generate much smaller AC loss than the single pancake type with flux diverters when they generate the same center magnetic field.