Search Results (101)

Nanozymes, as a new generation of artificial enzymes, have attracted increasing attention in the field of biomedicine due to their multiple enzymatic characteristics, multi-functionality, low cost, and high stability. Among them, carbon dot nanozymes (CDzymes) possess excellent enzymatic-like catalytic activity and biocompatibility and have been developed for various diagnostic and therapeutic studies of diseases. Here, we briefly review the representative research on CDzymes in recent years, including their synthesis, modification, and applications, especially in orthopedic diseases, including osteoarthritis, osteoporosis, osteomyelitis, intervertebral disc degenerative diseases, bone tumors, and bone injury repair and periodontitis. Additionally, we briefly discuss the potential future applications and opportunities and challenges of CDzymes. We hope this review can provide some reference opinions for CDzymes and offer insights for promoting their application strategies in the treatment of orthopedic disease. Full article

Background and Objective: Intervertebral disc degeneration (IVDD) is a leading cause of lower back pain with limited regenerative treatments. Among emerging regenerative approaches, growth factor-based therapies, such as recombinant human transforming growth factor-beta (Rh-TGF-β), have shown potential for disc regeneration but are hindered by rapid degradation and uncontrolled release by direct administration. Additionally, mechanical stress elevates heat shock protein 90 (HSP-90), impairing cell function and extracellular matrix (ECM) production. This study aimed to investigate a dual self-cross-linked alginate di-aldehyde (ADA) hydrogel system for the sustained delivery of Rh-TGF-β and epigallocatechin gallate (EGCG) to enhance protein stability, regulate release, and promote disc regeneration by targeting both regenerative and stress-response pathways. Methods: ELISA and UV-Vis spectrophotometry assessed Rh-TGF-β and EGCG release profiles. A rat tail IVDD model was established with an Ilizarov-type external fixator for loading, followed by hydrogel treatment with or without bioactive agents. Disc height, tissue structure, and protein expression were evaluated via radiography, histological staining, immunohistochemistry, and Western blotting. Results: The hydrogel demonstrated a biphasic release profile with 100% Rh-TGF-β released over 60 days and complete EGCG release achieved within 15 days. Treated groups showed improved disc height, structural integrity, and proteoglycan retention revealed by histological analysis and elevated HSP-90 expression by immunohistochemistry. In contrast, Western blot analysis confirmed that EGCG effectively downregulated HSP-90 expression, suggesting a reduction in mechanical stress-induced degeneration. Conclusions: ADA hydrogel effectively delivers therapeutic agents, offering a promising strategy for IVDD treatment. Full article

The torsional, lateral, and axial vibrations that occur during drilling operations have negative effects on the drilling equipment. These negative effects can cause huge economic impacts, as the failure of drilling tools results in wasted materials, non-productive time, and substantial expenses for equipment repairs. Many researchers have tried to reduce these vibrations and have tested several models in their studies. In most of these models, the drill string used in oil wells behaves like a rotating torsion pendulum (mass spring), represented by different discs. The top drive (with the rotary table) and the BHA (with the drill pipes) have been considered together as a linear spring with constant torsional stiffness and torsional damping coefficients. In this article, three models with different degrees of freedom are considered, with the aim of analyzing the effect of variations in the stiffness and damping coefficients on the severity of torsional vibrations. A comparative study has been conducted between the three models for dynamic responses to parametric variation effects. To ensure the relevance of the considered models, the field data of torsional vibrations while drilling were used to support the modeling assumption and the designed simulation scenarios. The main novelty of this work is its rigorous comparative analysis of how the stiffness and damping coefficients influence the severity of torsional vibrations based on field measurements, which has a direct application in operational energy efficiency and equipment reliability. The results demonstrated that the variation of the damping coefficient does not significantly affect the severity of the torsional vibrations. However, it is highly recommended to consider all existing frictions in the tool string to obtain a reliable torsional vibration model that can reproduce the physical phenomenon of stick–slip. Furthermore, this study contributes to the improvement of operational energy efficiency and equipment reliability in fossil energy extraction processes. Full article

The friction surfacing (FS) process has emerged over the past few years as a method for joining both similar and dissimilar materials, for volume damage repair of defective components, and for corrosion protection. The possibility to produce a metallic coating by FS, without melting the material, classifies this technique as distinct from other standard methods. This unconventional deposition method is based on the severe plastic deformation that appears on a rotating metallic rod (consumable material) pressed against the substrate under an axial load. The present study aims to investigate the tribological properties and corrosion resistance provided by the aluminum-based FS coatings deposited onto a structural S235 steel substrate and further modified by plasma electrolytic oxidation (PEO). During the PEO treatment, the formation of a ceramic film is enabled, while the hardness, chemical stability, corrosion, and wear resistance of the modified surfaces are considerably increased. The morpho-structural characteristics and chemical composition of the PEO-modified FS coatings are further investigated using scanning electron microscopy combined with energy dispersive spectroscopy analysis and X-ray diffraction. Dry sliding wear testing of the PEO-modified aluminum-based coatings was carried out using a ball-on-disc configuration, while the corrosion resistance was electrochemically evaluated in a 3.5 wt.% NaCl solution. The corrosion rates of the aluminum-based coatings decreased significantly when the PEO treatment was applied, while the wear rate was substantially reduced compared to the untreated aluminum-based coating and steel substrate, respectively. Full article

Background/Objectives: Lumbar disc herniation (LDH) is the most common condition associated with low back pain, and it adversely impacts individuals’ health. The interplay between energy metabolism and apoptosis is critical, as the loss of viable cells in the intervertebral disc (IVD) can lead to a cascade of degenerative changes. Efferocytosis is a key biological process that maintains homeostasis by removing apoptotic cells, resolving inflammation, and promoting tissue repair. Therefore, enhancing mitochondrial energy metabolism and efferocytosis function in IVD cells holds great promise as a potential therapeutic approach for LDH. Methods: In this study, energy metabolism and efferocytosis-related differentially expressed genes (EMERDEGs) were identified from the transcriptomic datasets of LDH. Machine learning approaches were used to identify key genes. Functional enrichment analyses were performed to elucidate the biological roles of these genes. The functions of the hub genes were validated by RT-qPCR. The CIBERSORT algorithm was used to compare immune infiltration between LDH and Control groups. Additionally, we used single-cell RNA sequencing dataset to analyze cell-specific expression of the hub genes. Results: By using bioinformatics methods, we identified six EMERDEGs hub genes (IL6R, TNF, MAPK13, ELANE, PLAUR, ABCA1) and verified them using RT-qPCR. Functional enrichment analysis revealed that these genes were primarily associated with inflammatory response, chemokine production, and cellular energy metabolism. Further, we identified candidate drugs as potential treatments for LDH. Additionally, in immune infiltration analysis, the abundance of activated dendritic cells, neutrophils, and gamma delta T cells varied significantly between the LDH group and Control group. The scRNA-seq analysis showed that these hub genes were mainly expressed in chondrocyte-like cells. Conclusions: The identified EMERDEG hub genes and pathways offer novel insights into the molecular mechanisms underlying LDH and suggest potential therapeutic targets. Full article

Due to the limited regeneration of cartilage, new implant materials are needed. Biodegradable polymers poly-(D,L)-lactide-ε-caprolactone-methacrylate (LCM) and polyamid-ε-caprolactone-methacrylate (ACM) were recently established and coated with heparin, making them able to prevent blood coagulation and cartilage mineralization. The aim of this study was to analyze the suitability of LCM and ACM alone or coated with heparin (the latter are abbreviated as LCMH and ACMH, respectively) as implant material for cartilage repair. Therefore, mesenchymal stem cells were chondrogenically differentiated in 2D cultures with polymer discs. Differentiation was induced by the supplementation of cell medium with dimethyloxalylglycine, TGF-β, and BMP2. After 5 days, no increase in proinflammatory factors was observed. Cell viability declined on ACM and ACMH discs. During early chondrogenesis, SOX9 expression increased on LCM and LCMH discs, while TRPV4 expression decreased on ACMH discs. At day 20, the level of collagen type II increased on LCM, LCMH, and ACM discs, demonstrating the ability of chondrogenic development on these implants. In summary, coating with heparin showed no advantages compared to pure LCM and ACM. For cartilage repair, LCM is more suitable than ACM in this 2D in vitro model, which needs to be verified by long-term 3D models and in vivo studies. Full article

Background/Objectives: Canine intervertebral disc herniation (IVDH) is an important musculoskeletal pathology. Unlike in humans, IVDH mechanisms in dogs are underinvestigated from a system-level integrative omics point of view. The aim of this study was to identify key serum molecular players in canine IVDH. Methods: An integrative multi-omics approach combining high-resolution LC-MS-based untargeted metabolomics and tandem mass tag (TMT)-based proteomics was applied. Additionally, serum zinc concentration was determined by spectrophotometry. Results: Nineteen serum metabolites were differentially abundant in IVDH dogs. Metabolite analysis highlighted dysregulation in lipoic acid and branched-chain amino acid (BCAA) metabolism, with elevated levels of valine, leucine, and isoleucine in IVDH. These findings suggest disrupted energy, nitrogen, and neurotransmitter metabolism, potentially contributing to the IVDH pathophysiology. Additionally, lower serum uridine, possibly influenced by BCAA accumulation, was observed, indicating altered neuroinflammatory responses. ELISA validation confirmed elevated serum levels of zinc-α2-glycoprotein (ZAG), alpha-1-microglobulin/bikunin precursor (AMBP), and vitronectin (VTN) in IVDH, supporting immune modulation and neuroprotective mechanisms. Serum prekallikrein (KLKB1) and Protein C inhibitor (SERPINA5), involved in fibrin cloth formation, were found to be lowered in IVDH patients. Pathway enrichment revealed disturbances in aromatic amino acid biosynthesis, with elevated phenylalanine, tyrosine, and tryptophan influencing neurotransmission and inflammation. In addition, elevated serum Zn concentration emphasized its antioxidant importance in immune response, wound healing, and neuropathic pain signaling. Conclusions: Integration with our prior CSF multi-omics data reinforced the relevance of identified molecules in IVDH-associated neurodegeneration, inflammation, and repair processes. This study offers insight into potential diagnostic biomarkers and therapeutic targets for canine IVDH through serum-based molecular profiling. Full article

After linear differential systems in the plane, the easiest systems are quadratic polynomial differential systems in the plane. Due to their nonlinearity and their many applications, these systems have been studied by many authors. Such quadratic polynomial differential systems have been divided into ten families. Here, for two of these families, we classify all topologically distinct phase portraits in the Poincaré disc. These two families have already been studied previously, but several mistakes made there are repaired here thanks to the use of a more powerful technique. This new technique uses the invariant theory developed by the Sibirskii School, applied to differential systems, which allows to determine all the algebraic bifurcations in a relatively easy way. Even though the goal of obtaining all the phase portraits of quadratic systems for each of the ten families is not achievable using only this method, the coordination of different approaches may help us reach this goal. Full article

Background: Intervertebral disc degeneration (IVDD) is a major cause of chronic back pain. Recent studies suggest that ferroptosis, a form of cell death, contributes to the degeneration of nucleus pulposus cells (NPCs). This study explores a novel therapeutic strategy using cell-free fat extract (CEFFE), rich in cytokines, to mitigate IVDD by inhibiting oxidative stress-induced ferroptosis. Methods: In vitro, NPC degeneration was induced by TNF-α/TBHP. The effects of CEFFE on matrix metabolism were evaluated using Western blotting, RT-qPCR, and high-density culture, with regenerative effects measured via CCK-8 assays. Ferroptosis was assessed by Western blotting, immunofluorescence, and electron microscopy. In vivo, rats with caudal IVDD were treated with CEFFE for 4 weeks, and therapeutic efficacy was evaluated through imaging and histological analysis. Results: In vitro, CEFFE reduced TNF-α-induced inflammation and promoted matrix synthesis by inhibiting MAPK and NF-κB pathways. It also activated NRF2 to prevent TBHP-induced ferroptosis. In rats, CEFFE facilitated nucleus pulposus repair and significantly slowed disc degeneration. Conclusions: CEFFE is a promising strategy to delay IVDD progression by inhibiting ferroptosis, offering potential therapeutic benefits for disc degeneration. Full article

Cellular infiltration into traditional electrospun nanofibers (NFs) is limited due to their dense structures. We were able to obtain polycaprolactone (PCL) NFs with variable and defined pore sizes and thicknesses by using a customized programmed NF collector that controls the moving speed during electrospinning. NFs obtained by this method were tested in vitro and have shown better cell proliferation within the NFs with larger pore sizes. This study investigated in vivo host cell migration and neovascularization within implanted porous PCL NF discs using a mouse pouch model. Four types of PCL NFs were prepared and classified based on the electrospinning speed: NF-zero (static control), NF-low (0.085 mm/min), NF-mid (0.158 mm/min) and NF-high (0.232 mm/min) groups. With the increase in the speed, we observed an increase in the pore area; NF-zero (11.6 ± 6.2 μm²), NF-low (37.4 ± 28.6 μm²), NF-mid (67.6 ± 54.8 μm²), and NF-high (292.3 ± 286.5 μm²) groups. The NFs were implanted into air pouches of BALB/cJ mice. Mice without NFs served as control. Animals were sacrificed at 7 and 28 days after the implantation. Pouch tissues with implanted NFs were collected for histology (n = three per group and time point). The efficiency of the tissue penetration into PCL NF sheets was closely linked to the pore size and area. NFs with the highest pore area had more efficient tissue migration and new blood vessel formation compared to those with a smaller pore area. No newly formed blood vessels were observed in NF-zero sheets up to 28 days. We believe that a porous NF scaffold with a controllable pore size and thickness has great potential for tissue repair/regeneration and for other healthcare applications. Full article

Background/Objectives: Bioactive materials are gaining increased popularity as materials of choice for pulpal regeneration. A similar trend is emerging with root repair materials; however, there is a significant gap in the literature about cementogenic ability of bioceramic repair materials on the periodontal ligament cells. The aim of the present study was to investigate the effect of bioceramic materials (Biodentine and Bio-C Repair) on the cementogenesis potential of the periodontal ligament stem cells (PDLSCs). Methods: PDLSCs were isolated using the enzymatic digestion approach from sound extracted teeth. Material extracts were prepared on rubber discs and immersed in fresh growth medium for 24 h at 37 °C. Reverse transcription–quantitative polymerase chain reaction (RT-qPCR) was used to detect the mRNA expression levels of cementogenic markers cementum protein 1 (CEMP1), Cementum attachment protein (CAP), pathway markers transforming growth factor β1(TGF-β1), bone morphogenic protein 2 (BMP2), and inflammatory marker IL-6. Results: Both materials (Biodentine and Bio-C Repair) showed significantly higher gene expressions when compared to the control groups. The gene expression with Bio-C Repair significantly increased when compared with Biodentine, except for TGF-β1 expression, where both materials exhibited similar results. Conclusions: Bio-C Repair demonstrated increased gene expression of cementogenic markers compared to Biodentine under the tested conditions. Further in vivo studies are deemed necessary to translate the findings from this study into clinical practice. Full article

This in vitro study investigates the impact of the chemical modification of resin composite surfaces on repair bond strength of micro-hybrid resin composite material. First, 7 mm circular × 3 mm thick resin composite disks were prepared using teflon molds. Then, 50 specimens out of 100 were allocated for stimulated aging using a thermo-cycling (10,000 cycles) device. Both the 24 h and 1-year-aged composite discs were embedded in epoxy resin using a 2.5 cm wide × 1.5 cm thick circular mold. The surfaces were treated with Clearfil S3 bond alone or with the additional application of silane or porcelain primer. The other two groups were bonded with CRB bond with or without a porcelain primer. Using a teflon mold, a 2 mm circular and 3 mm high repair composite cylinder was built on the treated surfaces. The specimens were then stressed to de-bond by applying shear force to measure repair bond strength, and they were observed under the microscope to determine the failure pattern. The data were analyzed using SPSS26.0. Univariate analysis showed a significant effect (p = 0.013) of the bonding protocol on the repair bond strength; however, the effect of aging was insignificant (p = 0.170). The S3 bond with additional silane and the CRB bond showed the significantly higher repair bond strength of the 1-year-aged micro-hybrid composite. However, in case of 24 h aged specimens, the repair bond strength was statistically insignificant among the tested groups (p = 0.340). Chemical surface modification with silane has the potential to improve the repair bond strength of micro-hybrid resin composite materials. Full article

Royal jelly and medical grade honey are traditionally used in treating wounds and infections, although their effectiveness is often variable and insufficient. To overcome their limitations, we created novel amphiphiles by modifying the main reparative and antimicrobial components, queen bee acid (hda) and 10-hydroxyl-decanoic acid (hdaa), through peptide bonding with specific tripeptides. Our molecular design incorporated amphiphile targets as being biocompatible in wound healing, biodegradable, non-toxic, hydrogelable, prohealing, and antimicrobial. The amphiphilic molecules were designed in a hda(hdaa)-aa1-aa2-aa3 structural model with rational selection criteria for each moiety, prepared via Rink/Fmoc-tBu-based solid-phase peptide synthesis, and structurally verified by NMR and LC–MS/MS. We tested several amphiphiles among those containing moieties of hda or hdaa and isoleucine–leucine–aspartate (ILD-amidated) or IL-lysine (ILK-NH₂). These tests were conducted to evaluate their prohealing and antimicrobial hydrogel properties. Our observation of their hydrogelation and hydrogel-rheology showed that they can form hydrogels with stable elastic moduli and injectable shear-thinning properties, which are suitable for cell and tissue repair and regeneration. Our disc-diffusion assay demonstrated that hdaa-ILK-NH₂ markedly inhibited Staphylococcus aureus. Future research is needed to comprehensively evaluate the prohealing and antimicrobial properties of these novel molecules modified from hda and hdaa with tripeptides. Full article

Background/Objectives: Recurrent lumbar disc herniation (RLDH) refers to a lumbar disc herniation (LDH) that recurs at the same level, location, and side following surgical repair. This study aimed to evaluate the efficacy of transforaminal epidural steroid injection (TESI) and dorsal root ganglion pulsed radiofrequency (DRG PRF) therapy with and without caudal epidural steroid injection (CESI) for the treatment of lumbar radicular pain (LRP) associated with RLDH. Methods: This retrospective cohort study included 57 patients treated for RLDH in a hospital pain clinic between September 2022 and February 2024. A total of 27 patients received TESI and DRG PRF therapy (Group 1) and 30 patients received TESI, DRG PRF, and CESI therapy (Group 2). We evaluated patient age, sex, symptom duration, pain medication use, number of prior LDH operations, presence of stabilization on magnetic resonance imaging (MRI), intervention received, lumbar level and side of the intervention, and Numeric Rating Scale (NRS) pain scores before and at 1, 3, and 6 months post-procedure. Treatment success was defined as an NRS score at least 50% or 4 points lower than the pre-procedure score at post-procedure 6 months. Results: There was no significant difference in NRS scores between the groups during the 6-month follow-up period. Moreover, NRS scores did not differ based on the presence of stabilization on MRI or the use of pain medication (p > 0.05). Conclusions: TESI and DRG PRF therapy were effective in the treatment of LRP associated with RLDH over a 6-month follow-up period, and adding CESI did not increase treatment success. Full article

Intervertebral disc degeneration, which leads to low back pain, is the most prevalent musculoskeletal condition worldwide, significantly impairing quality of life and imposing substantial socioeconomic burdens on affected individuals. A major impediment to the development of any prospective cell-driven recovery of functional properties in degenerate IVDs is the diminishing IVD cell numbers and viability with ageing which cannot sustain such a recovery process. However, if IVD proteoglycan levels, a major functional component, can be replenished through an orthobiological process which does not rely on cellular or nutritional input, then this may be an effective strategy for the re-attainment of IVD mechanical properties. Furthermore, biomimetic proteoglycans (PGs) represent an established polymer that strengthens osteoarthritis cartilage and improves its biomechanical properties, actively promoting biological repair processes. Biomimetic PGs have superior water imbibing properties compared to native aggrecan and are more resistant to proteolytic degradation, increasing their biological half-life in cartilaginous tissues. Methods have also now been developed to chemically edit the structure of biomimetic proteoglycans, allowing for the incorporation of bioactive peptide modules and equipping biomimetic proteoglycans as delivery vehicles for drugs and growth factors, further improving their biotherapeutic credentials. This article aims to provide a comprehensive overview of prospective orthobiological strategies that leverage engineered proteoglycans, paving the way for novel therapeutic interventions in IVD degeneration and ultimately enhancing patient outcomes. Full article