Remove the infected interbody cage using endoscopy in lumbar spine revision surgery: A case series and technique report.

BACKGROUND: Current revision surgery to remove the infected interbody cage following transforaminal lumbar interbody fusion (TLIF) surgery is challenging and traumatic. The purpose of this study is to introduce a novel surgical technique to remove the infected interbody cage for chronic infection. METHODS: Three patients with chronic infection following TLIF surgery underwent revision surgery. Instrumentations were removed and a spinal endoscope was obliquely inserted to the disc space through the initial annular breach. Under endoscope, the cage was found, released, turned around, and dragged to the posterior edge of the disc space. The cage was then removed without distracting the dural sac and nerve roots. For two cases, appropriately sized structural iliac bone grafts were used for interbody fusion without extra instrumentations. RESULTS: Using endoscope, the interbody cage was easy to identify and expose without disrupting the dural sac and nerve roots. With various endoscopic tools, the cage was easily released and removed. In this case series, the infected interbody cage was removed within thirty minutes without dural sac rupture and nerve root injury. The infection was controlled after the surgery, and the patients obtained good clinical outcomes. At 6-month follow-up, bony fusion was achieved in two patients who underwent interbody fusion. CONCLUSIONS: This endoscopy assisted technique simplified the revision surgery for chronic infection followed TLIF surgery, with the advantages of no disruption of the neural tissues, bright surgical field and complete disc debridement.

Synergistically targeting synovium STING pathway for rheumatoid arthritis treatment.

Rheumatoid arthritis (RA) is a common autoimmune disease leading to pain, disability, and even death. Although studies have revealed that aberrant activation of STING was implicated in various autoimmune diseases, the role of STING in RA remains unclear. In the current study, we demonstrated that STING activation was pivotal in RA pathogenesis. As the accumulation of dsDNA, a specific stimulus for STING, is a feature of RA, we developed a spherical polyethyleneimine-coated mesoporous polydopamine nanoparticles loaded with STING antagonist C-176 (PEI-PDA@C-176 NPs) for treating RA. The fabricated NPs with biocompatibility had high DNA adsorption ability and could effectively inhibit the STING pathway and inflammation in macrophages. Intra-articular administration of PEI-PDA@C-176 NPs could effectively reduce joint damage in mice models of dsDNA-induced arthritis and collagen-induced arthritis by inhibiting STING pathway. We concluded that materials with synergistic effects of STING inhibition might be an efficacious strategy to treat RA.

Scavenging of reactive oxygen species can adjust the differentiation of tendon stem cells and progenitor cells and prevent ectopic calcification in tendinopathy.

Tendinopathy is a common disorder that leads to pain and impaired quality of life. Recent studies revealed that osteogenic differentiation of tendon stem/progenitor cells (TSPCs) played an important role in the pathogenesis of tendon calcification and tendinopathy. In this study, we found that the growth hormone-releasing hormone agonist (GA) can prevent matrix degradation and osteogenic differentiation in TSPCs. As oxidative stress is a key factor in the osteogenic differentiation of TSPCs, we used bovine serum albumin/heparin nanoparticles (BHNPs), which have biocompatibility and drug loading capacity, to scavenge reactive oxygen species (ROS) and achieve sustained release of GA at the site of inflammation. The newly developed BHNPs@GA had a synergetic effect on reducing ROS production in TSPCs. In addition, BHNPs@GA effectively inhibited tendon calcification and promoted collagen formation in a rat model of tendinopathy. Focusing on the ROS underlying the differentiation and dedifferentiation of TSPCs, this work demonstrated that sustained release of GA targeting ROS and ectopic ossification is a practical therapeutic strategy for treating tendinopathy. STATEMENT OF SIGNIFICANCE: Osteogenic differentiation of tendon stem/progenitor cells (TSPCs) plays an important role in the pathogenesis of ectopic calcification in tendinopathy. In this study, we found that growth hormone-releasing hormone agonist (GA) can reduce reactive oxygen species (ROS) production and adjust TSPCs differentiation. Bovine serum albumin/heparin nanoparticles (BHNPs) were developed to encapsulate GA and achieve sustained release of GA at the site of inflammation. The developed compound, BHNPs@GA, with a synergistic effect of inhibiting ROS and thus, can effectively adjust TSPCs differentiation, inhibit tendon calcification, and promote collagen formation in tendinopathy. This study highlighted the role of ROS underlying the differentiation and dedifferentiation of TSPCs in tendinopathy, and findings may help to identify new therapeutic targets and develop novel strategy for treating tendinopathy.

Lumbosacral Transitional Vertebra Contributed to Lumbar Spine Degeneration: An MR Study of Clinical Patients.

We aimed to comprehensively characterize degenerative findings associated with various types of lumbosacral transitional vertebra (LSTV) on magnetic resonance images. Three hundred and fifty patients with LSTV (52.3 ± 10.9 years), including 182 Castellvi type I, 107 type II, 43 type III, and 18 type IV, and 179 controls without LSTV (50.6 ± 13.1 years), were studied. Discs, endplates, and posterior vertebral structures were assessed and compared to those of controls for the most caudal three discs on MRIs. There were no differences in degenerative findings between patients with type I LSTV and controls. For types III and IV, the transitional discs had smaller sizes, lower Pfirrmann scores, and lower rates of disc bulging (2.3% and 5.6% vs. 39.1%), osteophytes (2.3% vs. 15.1%), disc herniation (2.3% and 5.6% vs. 31.8%), and Modic changes (2.3% and 5.6% vs. 16.8%) than controls. However, the cranial discs had more severe Pfirrmann scores, disc narrowing and spinal canal narrowing, and greater rates of disc herniation (41.9% and 50.0% vs. 25.7%), endplate defects (27.9% and 33.3% vs. 14.4%) and spondylolisthesis (18.6% vs. 7.3%) than controls. Type II LSTV was associated with degenerative findings in the cranial segments but to a lesser degree, as compared with type III/IV LSTV. Thus, Castellvi type III/IV LSTV predisposed the adjacent spinal components to degeneration and protected the transitional discs. Type II LSTV had significant effects in promoting transitional and adjacent disc degeneration. Type I LSTV was not related to spinal degeneration.

A Combined Cyanine/Carbomer Gel Enhanced Photodynamic Antimicrobial Activity and Wound Healing.

As a non-invasive and non-specific therapeutic approach, photodynamic therapy (PDT) has been used to treat antibiotic-resistant bacteria with encouraging efficacy. Inspired by light, the photosensitizers can produce excessive reactive oxygen species (ROS) and, thus, effectively destroy or kill bacteria. Cyanine (Cy), a traditional photosensitizer for PDT, has the advantages of low cytotoxicity and high ROS yield. Yet, the water solubility and photostability for Cy are poor, which substantially limit its antibacterial efficiency and clinical translation. Herein, we combined Cy with carbomer gel (CBMG) to form a photodynamic Cy-CBMG hydrogel. In this system, Cy was evenly dispersed in CBMG, and CBMG significantly improved the water solubility and photostability of Cy via electrostatic interactions. The developed Cy-CBMG gel had less photodegradation under laser irradiation and thus can effectively elevate ROS accumulation in bacteria. The Cy-CBMG compound presented remarkable ROS-induced killing efficacy against methicillin-resistant Staphylococcus aureus (93.0%) and extended-spectrum ß-lactamase-producing Escherichia coli (88.7%) in vitro. Moreover, as a potential wound dressing material, the Cy-CBMG hydrogel exhibited excellent biocompatibility and effective antimicrobial ability to promote wound healing in vivo. Overall, this work proposed a practical strategy to synthesize a photosensitizer-excipient compound to enhance the photophysical property and antibacterial efficacy for PDT.

A thermosensitive, reactive oxygen species-responsive, MR409-encapsulated hydrogel ameliorates disc degeneration in rats by inhibiting the secretory autophagy pathway.

Lumbar disc degeneration is a common cause of chronic low back pain and an important contributor to various degenerative lumbar spinal disorders. However, currently there is currently no effective therapeutic strategy for treating disc degeneration. The pro-inflammatory cytokine interleukin-1ß (IL-1ß) mediates disc degeneration by inducing apoptotic death of nucleus pulposus (NP) cells and degradation of the NP extracellular matrix. Here, we confirmed that extracellular secretion of IL-1ß via secretory autophagy contributes to disc degeneration, and demonstrate that a thermosensitive reactive oxygen species (ROS)-responsive hydrogel loaded with a synthetic growth hormone-releasing hormone analog (MR409) can protect against needle puncture-induced disc degeneration in rats. Methods: The expression levels of proteins related to secretory autophagy such as tripartite motif-containing 16 (TRIM16) and microtubule-associated protein light chain 3B (LC3B) were examined in human and rat disc tissues by histology and immunofluorescence. The effects of TRIM16 expression level on IL-1ß secretion were examined in THP-1 cells transfected with TRIM16 plasmid or siRNA using ELISA, immunofluorescence, and immunoblotting. The in vitro effects of MR409 on IL-1ß were examined in THP-1 cells and primary rat NP cells using ELISA, immunofluorescence, immunoblotting, and qRT-PCR. Further, MR409 was subcutaneously administered to aged mice to test its efficacy against disc degeneration using immunofluorescence, X-ray, micro-CT, and histology. To achieve controllable MR409 release for intradiscal use, MR409 was encapsulated in an injectable ROS-responsive thermosensitive hydrogel. Viscosity, rheological properties, release profile, and biocompatibility were evaluated. Thereafter, therapeutic efficacy was assessed in a needle puncture-induced rat model of disc degeneration at 8 and 12 weeks post-operation using X-ray, magnetic resonance (MR) imaging, histological analysis, and immunofluorescence. Results: Secretory autophagy-related proteins TRIM16 and LC3B were robustly upregulated in degenerated discs of both human and rat. Moreover, while upregulation of TRIM16 facilitated, and knockdown of TRIM16 suppressed, secretory autophagy-mediated IL-1ß secretion from THP-1 cells under oxidative stress, MR409 inhibited ROS-induced secretory autophagy and IL-1ß secretion by THP-1 cells as well as IL-1ß-induced pro-inflammatory and pro-catabolic effects in rat NP cells. Daily subcutaneous injection of MR409 inhibited secretory autophagy and ameliorated age-related disc degeneration in mice. The newly developed ROS-responsive MR409-encapsulated hydrogel provided a reliable delivery system for controlled MR409 release, and intradiscal application effectively suppressed secretory autophagy and needle puncture-induced disc degeneration in rats. Conclusion: Secretory autophagy and associated IL-1ß secretion contribute to the pathogenesis of disc degeneration, and MR409 can effectively inhibit this pathway. The ROS-responsive thermosensitive hydrogel encapsulated with MR409 is a potentially efficacious treatment for disc degeneration.