RESUMEN
BACKGROUND: Intervertebral disc degeneration (IVDD) is a common cause of chronic low back pain (LBP) and a socioeconomic burden worldwide. Conservative therapies and surgical treatments provide only symptomatic pain relief without promoting intervertebral disc (IVD) regeneration. Therefore, the clinical demand for disc regenerative therapies for disc repair is high. METHODS: In this study, we used a rat tail nucleotomy model to develop mechanically stable collagen-cryogel and fibrillated collagen with shape-memory for use in minimally invasive surgery for effective treatment of IVDD. The collagen was loaded with hyaluronic acid (HA) into a rat tail nucleotomy model. RESULTS: The shape-memory collagen structures exhibited outstanding chondrogenic activities, having completely similar physical properties to those of a typical shape-memory alginate construct in terms of water absorption, compressive properties, and shape-memorability behavior. The treatment of rat tail nucleotomy model with shape-memory collagen-cryogel/HA alleviated mechanical allodynia, maintained a higher concentration of water content, and preserved the disc structure by restoring the matrix proteins. CONCLUSION: According to these results, the collagen-based structure could effectively repair and maintain the IVD matrix better than the controls, including HA only and shape-memory alginate with HA.
RESUMEN
Intervertebral disc (IVD) degeneration is a leading cause of back pain and precursor to more severe conditions, including disc herniation and spinal stenosis. While traditional growth factor therapies (e.g., TGFß) are effective at transiently reversing degenerated disc by stimulation of matrix synthesis, it is increasingly accepted that bioscaffolds are required for sustained, complete IVD regeneration. Current scaffolds (e.g., metal/polymer composites, non-mammalian biopolymers) can be improved in one or more IVD regeneration demands: biodegradability, noninvasive injection, recapitulated healthy IVD biomechanics, predictable crosslinking, and matrix repair induction. To meet these demands, tetrazine-norbornene bioorthogonal ligation was combined with gelatin to create an injectable bioorthogonal hydrogel (BIOGEL). The liquid hydrogel precursors remain free-flowing across a wide range of temperatures and crosslink into a robust hydrogel after 5-10 min, allowing a human operator to easily inject the therapeutic constructs into degenerated IVD. Moreover, BIOGEL encapsulation of TGFß potentiated histological repair (e.g., tissue architecture and matrix synthesis) and functional recovery (e.g., high water retention by promoting the matrix synthesis and reduced pain) in an in vivo rat IVD degeneration/nucleotomy model. This BIOGEL procedure readily integrates into existing nucleotomy procedures, indicating that clinical adoption should proceed with minimal difficulty. Since bioorthogonal crosslinking is essentially non-reactive towards biomolecules, our developed material platform can be extended to other payloads and degenerative injuries.
RESUMEN
Uropathogenic Escherichia coli (UPEC) is the most prevalent cause of urinary tract infections (UTIs). Biofilm formation and antibiotic resistance could be high among the causative agent. The purpose of this study was to determine antibiotic resistance, biofilm production, and biofilm-associated genes, bcsA and csgD, and sub-inhibitory hydrogen peroxide (H2O2) stimulation in UPEC for biofilm formation. A total of 71 UPEC were collected from a tertiary care hospital in Kathmandu and subjected to identify antibiotic susceptibility using Kirby-Bauer disk diffusion. The biofilm formation was assessed using microtiter culture plate method while pellicle formation was tested by a tube method. In representative 15 isolates based on biofilm-forming ability, bcsA and csgD were screened by conventional polymerase chain reaction, and treated with sub-lethal H2O2. The UPEC were found the most susceptible to meropenem (90.2%), and the least to ampicillin (11.3%) in vitro and 90.1% of them were multi-drug resistant (MDR). Most UPEC harbored biofilm-producing ability (97.2%), and could form pellicle at 37°C. Among representative 15 isolates, csgD was detected only among 10 isolates (66.67%) while bcsA gene was present in 13 isolates (86.67%). This study revealed that level of biofilm production elevated after sub-lethal H2O2 treatment (P = .041). These findings suggested that the pathogens are emerging as MDR. The biofilm production is high and the majority of selected strains contained bcsA and csgD genes. Pellicle formation test was suggestive to be an alternative qualitative method to screen biofilm production in UPEC. The sub-inhibitory concentration of H2O2 may contribute in increasing biofilm formation in UPEC.
RESUMEN
Intervertebral disc (IVD) degeneration can cause chronic lower back pain (LBP), leading to disability. Despite significant advances in the treatment of discogenic LBP, the limitations of current treatments have sparked interest in biological approaches, including growth factor and stem cell injection, as new treatment options for patients with chronic LBP due to IVD degeneration (IVDD). Gene therapy represents exciting new possibilities for IVDD treatment, but treatment is still in its infancy. Literature searches were conducted using PubMed and Google Scholar to provide an overview of the principles and current state of gene therapy for IVDD. Gene transfer to degenerated disc cells in vitro and in animal models is reviewed. In addition, this review describes the use of gene silencing by RNA interference (RNAi) and gene editing by the clustered regularly interspaced short palindromic repeats (CRISPR) system, as well as the mammalian target of rapamycin (mTOR) signaling in vitro and in animal models. Significant technological advances in recent years have opened the door to a new generation of intradiscal gene therapy for the treatment of chronic discogenic LBP.
