Core-Shell Structured Nanozyme with PDA-Mediated Enhanced Antioxidant Efficiency to Treat Early Intervertebral Disc Degeneration.

Early intervention during intervertebral disc degeneration (IDD) plays a vital role in inhibiting its deterioration and activating the regenerative process. Aiming at the high oxidative stress (OS) in the IDD microenvironment, a core-shell structured nanozyme composed of Co-doped NiO nanoparticle (CNO) as the core encapsulated with a polydopamine (PDA) shell, named PDA@CNO, was constructed, hoping to regulate the pathological environment. The results indicated that the coexistence of abundant Ni3+/Ni2+and Co3+/Co2+redox couples in CNO provided rich catalytic sites; meanwhile, the quinone and catechol groups in the PDA shell could enable the proton-coupled electron transfer, thus endowing the PDA@CNO nanozyme with multiple antioxidative enzyme-like activities to scavenge •O2-, H2O2, and •OH efficiently. Under OS conditions in vitro, PDA@CNO could effectively reduce the intracellular ROS in nucleus pulposus (NP) into friendly H2O and O2, to protect NP cells from stagnant proliferation, abnormal metabolism (senescence, mitochondria dysfunction, and impaired redox homeostasis), and inflammation, thereby reconstructing the extracellular matrix (ECM) homeostasis. The in vivo local injection experiments further proved the desirable therapeutic effects of the PDA@CNO nanozyme in a rat IDD model, suggesting great potential in prohibiting IDD from deterioration.

Propelling Multi-Modal Therapeutics of PEEK Implants through the Power of NO evolving Covalent Organic Frameworks (COFs).

The design and fabrication of NO-evolving core-shell nanoparticles (denoted as NC@Fe), comprised of BNN6-laden COF@Fe3 O4 nanoparticles, are reported. This innovation extends to the modification of 3D printed polyetheretherketone scaffolds with NC@Fe, establishing a pioneering approach to multi-modal bone therapy tailored to address complications such as device-associated infections and osteomyelitis. This work stands out prominently from previous research, particularly those relying on the use of antibiotics, by introducing a bone implant capable of simultaneous NO gas therapy and photothermal therapy (PPT). Under NIR laser irradiation, the Fe3 O4 NP core (photothermal conversion agent) within NC@Fe absorbs photoenergy and initiates electron transfer to the loaded NO donor (BNN6), resulting in controlled NO release. The additional heat generated through photothermal conversion further propels the NC@Fe nanoparticles, amplifying the therapeutic reach. The combined effect of NO release and PPT enhances the efficacy in eradicating bacteria over a more extensive area around the implant, presenting a distinctive solution to conventional challenges. Thorough in vitro and in vivo investigations validate the robust potential of the scaffold in infection control, osteogenesis, and angiogenesis, emphasizing the timeliness of this unique solution in managing complicated bone related infectious diseases.

Hollow Cobalt Sulfide Nanospheres with Highly Enzyme-like Antibacterial Activities to Accelerate Infected Wound Healing.

The emergence of nanozymes presents a promising alternative to antibiotics for reactive oxygen species-mediated broad-spectrum antimicrobial purposes, but nanozymes still face challenges of low therapeutic efficiency and poor biocompatibility. Herein, we creatively prepared a novel kind of hollow cobalt sulfide (CoS) nanospheres with a unique mesoporous structure that is able to provide numerous active sites for enzyme-like reactions. The results revealed that 50 µg/mL of CoS nanospheres exhibited strong peroxidase- and oxidase-like activities under physiological conditions with the assistance of a low concentration of hydrogen peroxide (H2O2, 100 µM) while possessing highly efficient GSH-depletion ability, which endowed CoS nanospheres with triple enzyme-like properties to combat bacterial infections. The in vitro experiments demonstrated that the CoS nanozyme displayed significant antibacterial effects against both Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli). The in vivo implantation showed that the synthesized CoS effectively eliminated bacteria and promoted the recovery of infected wounds in rats while exhibiting a low cytotoxicity. This study provides a promising treatment strategy to accelerate infected wound healing.

Injectable mesoporous bioactive glass/sodium alginate hydrogel loaded with melatonin for intervertebral disc regeneration.

Intervertebral disc degeneration (IDD) is a major contributing factor to both lower back and neck pain. As IDD progresses, the intervertebral disc (IVD) loses its ability to maintain its disc height when subjected to axial loading. This failure in the weight-bearing capacity of the IVD is a characteristic feature of degeneration. Natural polymer-based hydrogel, derived from biological polymers, possesses biocompatibility and is able to mimic the structure of extracellular matrix, enabling them to support cellular behavior. However, their mechanical performance is relatively poor, thus limiting their application in IVD regeneration. In this study, we developed an injectable composite hydrogel, namely, Mel-MBG/SA, which is similar to natural weight-bearing IVD. Mesoporous bioactive glasses not only enhance hydrogels, but also act as carriers for melatonin (Mel) to suppress inflammation during IDD. The Mel-MBG/SA hydrogel further provides a mixed system with sustained Mel release to alleviate IL-1ß-induced oxidative stress and relieve inflammation associated with IDD pathology. Furthermore, our study shows that this delivery system can effectively suppress inflammation in the rat tail model, which is expected to further promote IVD regeneration. This approach presents a novel strategy for promoting tissue regeneration by effectively modulating the inflammatory environment while harnessing the mechanical properties of the material.

Prognostic values of geriatric nutrition risk index on elderly patients after spinal tuberculosis surgery.

Background: Spinal tuberculosis (STB) is a significant public health concern, especially in elderly patients, due to its chronic and debilitating nature. Nutritional status is a critical factor affecting the prognosis of STB patients. The geriatric nutritional risk index (GNRI) has been established as a reliable predictor of adverse outcomes in various diseases, but its correlation with surgical outcomes in elderly STB patients has not been studied. Objective: The study aimed to assess the prognostic value of the GNRI in elderly patients with STB who underwent surgery. Methods: We conducted a retrospective analysis of medical records of elderly patients (65 years or older) diagnosed with active STB who underwent surgical treatment. Data collection included patient demographics, comorbidities, clinical history, laboratory testing, and surgical factors. GNRI was calculated using serum albumin levels and body weight. Postoperative complications were observed and recorded. The patients were followed up for at least 1 year, and their clinical cure status was assessed based on predefined criteria. Results: A total of 91 patients were included in the study. We found that a GNRI value of <98.63 g/dL was a cutoff value for predicting unfavorable clinical prognosis in elderly STB patients undergoing surgery. Patients with a low GNRI had higher Charlson Comorbidity Index scores, were more likely to receive red blood cell transfusions, and had a higher prevalence of overall complications, particularly pneumonia. The unfavorable clinical prognosis group had lower GNRI scores compared to the favorable prognosis group. Multivariate analysis showed that lower GNRI independently predicted unfavorable clinical outcomes in elderly STB patients. Conclusion: The study concluded that the GNRI is a valuable biomarker for predicting prognosis in elderly STB patients undergoing surgical intervention. Patients with lower GNRI scores had worse outcomes and a higher incidence of complications.

Bioinspired Construction of Annulus Fibrosus Implants with a Negative Poisson's Ratio for Intervertebral Disc Repair and Restraining Disc Herniation.

Inspired by the negative Poisson's ratio (NPR) effects of the annulus fibrosus (AF) in intervertebral discs (IVDs), we designed a re-entrant honeycomb model and then 3D printed it into a poly(ε-caprolactone) (PCL) scaffold with NPR effects, which was followed by in situ polymerization of polypyrrole (PPy), thus constructing a PPy-coated NPR-structured PCL scaffold (-vPCL-PPy) to be used as the AF implant for the treatment of lumbar herniated discs. Mechanical testing and finite element (FE) simulation indicated that the NPR composite implant could sustain axial spine loading and resist nucleus pulposus (NP) swelling while displaying uniform stress diffusion under NP swelling and contraction. More interestingly, the NPR-structured composite scaffold could also apply a reacting force to restrain NP herniation owing to the NPR effect. In addition, the in vitro biological assessment and in vivo implantation demonstrated that the NPR composite scaffold exhibited good biocompatibility and exerted the ability to restore the physiological function of the disc segments.

Letter to the editor regarding "efficacy and safety of platelet-rich plasma combined with hyaluronic acid versus platelet-rich plasma alone for knee osteoarthritis: a systematic review and meta-analysis".

In this letter to the editor, we discuss the article by Zhang et al., published recently in the Journal of Orthopaedic Surgery and Research. The authors reviewed the efficacy and safety of platelet-rich plasma combined with hyaluronic acid versus platelet-rich plasma alone for knee osteoarthritis. Whether the authors' purpose in grouping was to investigate the role of hyaluronic acid in the treatment of knee osteoarthritis is a question we would like to raise. In terms of the methodology of the study, combining randomized controlled trials with cohort studies in this meta-analysis is a methodological error. Secondly, the study methodology of the four included randomized controlled trial studies lacked a clear method of randomization. In addition to this, the completeness of the search needs to be taken into consideration. Some of the results of this study were highly heterogeneous, and no sensitivity analysis or meta-regression was performed to further analyse the sources of heterogeneity. The above issues will affect the conclusions of the article, and we believe this needs further improvement and discussion.

Treatment outcomes of injectable thermosensitive hydrogel containing bevacizumab in intervertebral disc degeneration.

Intervertebral disc (IVD) degeneration (IDD) is a common musculoskeletal disease and its treatment remains a clinical challenge. It is characterised by reduced cell numbers and degeneration of the extracellular matrix (ECM). Nucleus pulposus (NP) cells play a crucial role in this process. The purpose of this study is to explore the role of bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, in the treatment of IDD through local drug delivery. High expression of VEGF was observed in degenerating human and rat IVDs. We demonstrated that MMP3 expression was decreased and COL II synthesis was promoted, when VEGF expression was inhibited by bevacizumab, thereby improving the degree of disc degeneration. Thus, these findings provide strong evidence that inhibition of VEGF expression by local delivery of bevacizumab is safe and effective in ameliorating disc degeneration in rats. The injectable thermosensitive PLGA-PEG-PLGA hydrogels loaded with bevacizumab is a potential therapeutic option for disc degeneration.