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@HP^gel) 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@HP^gel 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.

Study Design.: Prospective cohort study. Objective.: To assess the differences in the clinical and radiological outcomes between oblique lateral interbody fusion (OLIF) and minimally invasive transforaminal lumbar interbody fusion (MI-TLIF). Summary of Background Data.: Nowadays, there is still a controversy regarding whether OLIF is superior to MI-TLIF in the management of degenerative lumbar disease. Methods.: Between August 3, 2019 and February 3, 2020, 137 patients were assigned to OLIF or MI-TLIF at their request and the surgeon's discretion: 71 in the OLIF group and 66 in the MI-TLIF group. The perioperative data, patient-reported outcomes, radiographic outcomes, and complications were compared between the two groups. Results.: The OLIF group showed shorter operation time (110.5 vs.183.8 minutes, P < 0.001), lesser estimated blood loss (123.1 vs. 232.0 mL, P < 0.001), shorter length of hospital stay (5.5 vs. 6.7 days, P < 0.001), and lower serum creatine kinase (CK) (1 day postoperatively) (376.0 vs. 541.8 IU/L, P < 0.01) than that of MI-TLIF group. Both groups showed no significant differences in the visual analog scale (VAS) scores of lower back and leg pain and the Oswestry Disability Index (ODI) scores preoperatively and at 1, 3, and 12 months postoperatively, respectively (P > 0.05). Compared with the MI-TLIF group, the OLIF group showed better restoration of disc height (DH) (4.7/4.6/4.7 vs. 3.7/3.7/3.7 mm, P < 0.01) and lumbar lordosis angle (LLA) (10.5°/10.8°/11.1° vs. 5.8°/5.7°/5.3°, P < 0.001), but not the value of segmental lordosis angle (SLA) (P > 0.05) at 1 day, 1 month, and 1 year postoperatively, respectively. The complication rate of OLIF was higher than that of MI-TLIF (29.4% vs. 9.7%, P < 0.01). Conclusion.: Compared with MI-TLIF, OLIF showed similar results in terms of patient-reported outcomes, restoration of SLA and fusion rate, and superior results with respect to restoration of DH and LLA, operation time, estimated blood loss, length of hospital stay, and serum CK levels (1 day postoperatively). Even though the complication rate of OLIF is higher than that of MI-TLIF, it does not bring persistent and substantial damage to the patients. Level of Evidence: 3

Chronic inflammatory diseases, such as intervertebral disc degeneration (IVDD), which affect the lives of hundreds of millions of people, still lack effective and precise treatments. In this study, a novel hydrogel system with many extraordinary properties is developed for gene–cell combination therapy of IVDD. Phenylboronic acid‐modified G5 PAMAM (G5‐PBA) is first synthesized, and therapeutic siRNA silencing the expression of P65 mixed with G5‐PBA (siRNA@G5‐PBA) is then embedded into the hydrogel (siRNA@G5‐PBA@Gel) based on multi‐dynamic bonds including acyl hydrazone bonds, imine linkage, π–π stacking, and hydrogen bonding interactions. Local and acidic inflammatory microenvironment‐responsive gene‐drug release can achieve spatiotemporal regulation of gene expression. In addition, gene‐drug release from the hydrogel can be sustained for more than 28 days in vitro and in vivo, greatly inhibiting the secretion of inflammatory factors and the subsequent degeneration of nucleus pulposus (NP) cells induced by lipopolysaccharide (LPS). Through prolonged inhibition of the P65/NLRP3 signaling pathway, the siRNA@G5‐PBA@Gel is verified to relieve inflammatory storms, which can significantly enhance the regeneration of IVD when combined with cell therapy. Overall, this study proposes an innovative system for gene–cell combination therapy and a precise and minimally invasive treatment method for IVD regeneration.

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.