Frontiers in Bioengineering and Biotechnology最新文献

Objective: This study aimed to compare the fixation performance differences between the traditional proximal femoral nail antirotation (PFNA), "II" proximal femoral bionic nail (PFBN), and proximal femoral total bionic nail (PFTBN) in the treatment of intertrochanteric femoral fractures complicated by lateral wall injury using finite element analysis. Additionally, it intended to explore the biomechanical effects of reamed versus unreamed techniques on these novel intramedullary nail devices.

Methods: Validated FEA models of intertrochanteric fractures (lateral wall injury) were constructed with 9 mm (unreamed) and 11 mm (reamed) medullary canals, followed by implantation of PFNA, "II" PFBN, or PFTBN. Under a vertical load of 2100 N, Von Mises Stress (VMS) and displacement of the femur and implants were quantified.

Results: Under a vertical load of 2100 N, in the unreamed condition, the PFTBN exhibited the lowest peak stress and displacement among the three devices, followed by the "II" PFBN, while the traditional PFNA showed the poorest performance. After reaming, all three implants demonstrated increased peak stress and slightly elevated peak displacement; however, PFTBN remained the most stable. Notably, reaming significantly reduced the overall peak stress of the femur. Collectively, PFTBN more effectively reduced the stress and displacement of both the femur and the implant under both reamed and unreamed conditions, with "II" PFBN showing intermediate efficacy. Both novel devices provided superior internal fixation stability compared to PFNA, which may contribute to a reduced risk of postoperative complications.

Conclusion: PFTBN outperforms "II" PFBN and PFNA in load/shear resistance for intertrochanteric fractures with lateral wall injury, regardless of reaming. "II" PFBN also shows superior stability to PFNA. Reaming increases nail-bone contact, mitigating femoral stress concentration and refracture risk. Both PFTBN and "II" PFBN are reliable fixation options with promising clinical utility.

Introduction: Abnormal mechanical loading is a significant pathogenic factor in intervertebral disc degeneration (IVDD), yet the underlying mechanotransduction mechanisms remain incompletely elucidated. This study aimed to investigate the role of integrin α5β1 as a key mechanosensor in regulating the autophagy-apoptosis balance under mechanically induced IVDD.

Methods: Bovine intervertebral discs (IVDs) with intact endplates were cultured in a bioreactor and subjected to dynamic mechanical loading, including physiological loading (PL: 0.02-0.2 MPa, 0.2 Hz) and degenerative loading (DL: 0.32-0.5 MPa, 5 Hz) for 3 and 7 days. Interventions involved the autophagy inhibitor 3-Methyladenine (3-MA), integrin α5β1-specific inhibitory peptide RGD (Arg-Gly-Asp), and the autophagy activator rapamycin. A systematic evaluation was performed, assessing disc height, histomorphology, cell viability, gene/protein expression, autophagy levels, and apoptosis.

Results: Degenerative loading induced progressive IVD degeneration, characterized by irreversible disc height loss, structural disruption, decreased cell viability, and extracellular matrix (ECM) metabolic imbalance. Treatment with 3-MA exacerbated these degenerative changes, confirming the protective role of autophagy. Integrin α5β1 exhibited distinct spatial distribution patterns: its expression was significantly upregulated in the nucleus pulposus (NP) and inner annulus fibrosus (IAF) under degenerative loading, whereas only the β1 subunit was increased in the outer annulus fibrosus (OAF). Functional experiments demonstrated that competitive inhibition of integrin α5β1 by RGD peptide significantly suppressed autophagy activity, exacerbated apoptosis, and promoted ECM degradation. Conversely, rapamycin alleviated degeneration by restoring autophagic flux. Mechanistically, degenerative loading suppressed the FAK/PI3K/AKT/mTOR pathway while upregulating ULK1, and these effects were partially reversed by RGD inhibition.

Discussion: The autophagy-apoptosis balance plays a critical regulatory role in IVDD progression, with integrin α5β1 serving as a crucial upstream mechanosensor that may exert its protective function through modulating the FAK/PI3K/AKT/mTOR pathway. The region-specific distribution of integrin subtypes determines the specificity of mechanotransduction across different disc areas. Targeting the integrin-autophagy axis and its associated signaling pathways may represent a potential therapeutic strategy for mitigating mechanically induced IVDD.

Introduction: Cervical spondylotic myelopathy (CSM) is a common degenerative disease of the cervical spine, for which anterior cervical discectomy and fusion (ACDF) serves as an effective surgical treatment. Recent studies have suggested that the quality of the paraspinal muscles, particularly the multifidus muscle, is closely related to postoperative outcomes; However, biomechanical evidence remains limited. The aim of this study is to investigate the biomechanical impact of varying paraspinal muscle mass on the cervical spine following ACDF.

Methods: A finite element model of the cervical spine, including vertebrae, intervertebral discs, ligaments, and implants (cage and screws), was developed based on CT data from a healthy volunteer. Three models simulating different postoperative states of the multifidus muscle were constructed: a postoperative muscle training model (120% muscle quality), a postoperative muscle atrophy model (80% muscle quality), and a control model (100% muscle quality). Flexion, extension, lateral bending, and rotational loads were applied to each model to analyze changes in adjacent segment disc pressure, implant stress distribution, capsular ligament stress, and range of motion (ROM).

Results: In the finite element models of different muscle quality groups after ACDF, the muscle atrophy model (80% muscle quality) showed a general increase in the intervertebral disc pressure of adjacent segments, especially during flexion-extension movements, which indicates an elevated risk of degeneration. Meanwhile, the stress values of implants such as cages and screws were increased, with more significant elevation observed during flexion and rotation. The capsular ligament stress was also elevated in the muscle atrophy model, and load overload was prone to occur during extension and rotation. In addition, muscle atrophy could lead to an increase in the ROM of adjacent segments. In contrast, all biomechanical indices of the muscle exercise model (120% muscle quality) were superior to those of the normal model.

Conclusion: Paraspinal muscle quality is a critical factor influencing biomechanical stability after ACDF. Muscle atrophy may increase the risk of adjacent segment degeneration and implant failure, while muscle strengthening contributes to enhancing postoperative stability. These results support that preoperative evaluation of paraspinal muscle status and targeted postoperative muscle strength training hold significant clinical implications for improving surgical prognosis.

Early carcinoma detection benefits from label-free, high-sensitivity surface plasmon resonance (SPR) biosensors. We computationally evaluated multilayer SPR architectures based on CaF₂/Cu/TiO₂/Graphene using the transfer-matrix method at 633 nm. Across 1-5 ng/mL, we analyzed reflectance, resonance-angle shifts, and near-field profiles, and derived sensitivity, detection accuracy (DA), figure of merit, and the limit of detection (LOD). The CaF₂/Cu/TiO₂/Graphene stack yielded the best performance, achieving 481.29°/RIU sensitivity and DA = 0.80, with pronounced evanescent-field confinement at the sensing interface. Under identical modeling conditions, this graphene-integrated configuration outperformed TiO₂-only and Cu-only baselines within the studied range. These results indicate a cost-effective platform for sensitive carcinoma biomarker detection. Calculation details for LOD and other metrics are provided in Methods, and practical considerations for experimental realization are discussed.

Introduction: Freshwater scarcity represents a major constraint for the sustainable industrial-scale cultivation of microalgae. This study investigates the feasibility of producing Scenedesmus almeriensis using seawater in 3.1 m³ tubular photobioreactors under winter-spring conditions. The appearance of algal predators represents a significant challenge in industrial facilities, and this research also explores whether seawater can serve as a strategic water source for more resilient and efficient production systems. Methods: Biomass productivity and microbial diversity were compared between freshwater and seawater-based cultures under batch and semi-continuous regimes at dilution rates of 0.1, 0.2, and 0.3 day^-1. The production was carried out in duplicate using identical tubular photobioreactors. Analytical determinations included measuring biomass concentration, chlorophyll fluorescence, and oxygen production via photorespirometry. Microbial diversity was assessed through microscopy and metagenomic analysis (18S and 16S rDNA) to identify taxonomic classifications and potential biotic contaminants. Results and Discussion: Maximum biomass concentrations reached 0.60 and 2.15 g·L^-1 in freshwater and seawater, respectively. Production using seawater led to a higher biomass productivity (0.18 g·L^-1·day^-1) compared to freshwater (0.06 g·L^-1·day^-1) at a fixed dilution rate of 0.1 day^-1. Seawater cultures exhibited greater stability and higher photosynthetic efficiency, with Scenedesmus dominating up to 70% of the microalgal community due to reduced contamination by zooplankton, fungi, and ciliates. In contrast, freshwater cultures were rapidly degraded by rotifers and anaerobic fungi, leading to a culture crash when dilution rates were increased. These findings highlight the potential of seawater to act as a biological barrier against contaminants while significantly reducing freshwater requirements in industrial microalgae production.

Corneal stromal lenticules obtained through small incision lenticule extraction (SMILE) procedures offer a valuable graft material for therapeutic applications. Current clinical utilization faces challenges due to intrinsic thinness (<140 μm) and restricted dimensions (generally around 6.6 mm). This study introduced a novel approach to enable the construction of customizable corneal grafts by stacking lenticules, achieving specific thickness and diameter for diverse corneal defects, using photo-crosslinked dual-network hydrogels based on methacrylated gelatin (GelMA). In vitro characterization confirmed the hydrogel's suitable morphological architecture, optical clarity, and excellent biocompatibility, establishing it as an optimal biological adhesive for sutureless graft implantation. This multi-lenticule encapsulation strategy using the hydrogels successfully reconstructed experimental rabbit corneal defects (7.0-mm diameter) in vivo. Over a 5-week postoperative period, the hydrogel demonstrated controlled biodegradation while maintaining structural integrity and optical functionality throughout tissue remodeling. It effectively adhered to the surrounding stromal tissues and supported epithelial regeneration over the transplanted grafts. The study demonstrates sutureless-free corneal stromal lenticule implantation, enabled by the GelMA-based photocrosslinked dual-network hydrogel, addressed the limitations of individual SMILE lenticules. The GelMA-based photocrosslinked dual-network hydrogel serves as both a biocompatible adhesive for multi-lenticule implantation and an optimal functional material for reconstructing corneal defects.

Background and purpose: Chondrogenesis is essential for cartilage repair and regeneration, particularly in treating osteoarthritis and cartilage injuries. While conventional therapies rely heavily on growth factors, recent interest has turned toward drug repurposing strategies involving small-molecule inhibitors. This study aims to evaluate the chondrogenic potential of selected bioactive compounds, with a particular focus on Trametinib, a MEK inhibitor.

Experimental approach: A library of 55 bioactive compounds was screened using high-content imaging and a 3D hydrogel model that mimics the native cartilage microenvironment. Cellular morphology, migration, and cytoskeletal organization were assessed to identify chondrogenic phenotypes. Trametinib, along with Panobinostat, SAHA, and Brefeldin A, was further evaluated via dose-response analyses and molecular assays to determine their impact on chondrogenic differentiation.

Key results: Trametinib was identified as a potent modulator of chondrogenesis-related cellular phenotypes. It significantly altered cell morphology, promoted a chondrogenic-like shape, and enhanced cell migration. Changes in actin organization were quantified using SER-Spot and SER-Ridge metrics, showing patterns consistent with chondrogenic differentiation. Molecular analysis revealed upregulation of Collagen II and aggrecan, key markers of cartilage formation.

Conclusion and implications: These findings support the potential of MEK inhibitors like Trametinib, and other selected bioactive compounds, as promising agents for cartilage regeneration. Their repurposing could offer innovative therapeutic strategies for treating cartilage-related disorders, including osteoarthritis.

Introduction: Occult hepatitis B virus infection (OBI) is a specific form of hepatitis B virus (HBV) infection characterized by testing negative for Hepatitis B surface antigen (HBsAg) with the presence of HBV DNA in the blood. Due to the complexity and high cost of HBV DNA testing, which is rarely included in routine physical examinations, leading to underdiagnosis of OBI. In this study, plasma visible-near-infrared (Vis-NIR) spectroscopy pattern recognition was employed to develop the discriminant analysis models for distinguishing between OBI from healthy (normal controls) plasma.

Methods: A total of 444 plasma samples from voluntary blood donors (OBI 204, normal controls 240) were collected, and their Vis-NIR spectra were measured. The samples were rigorously divided into training, prediction, and independent external validation sets. Partial least squares-discriminant analysis (PLS-DA) and k-nearest neighbor (kNN) were used as spectral classifiers; standard normal variate (SNV) and norris derivative filtering (NDF) were applied for spectral preprocessing. The integrated algorithm combining separation degree priority combination (SDPC) with wavelength step-by-step phase-out (WSP) was utilized for the optimal wavelength selection.

Results: The plasma spectral discriminant models for OBI and normal control were successfully established. Based on the optimal SNV-NDF preprocessed spectra, the SDPC-WSP-kNN and SDPC-WSP-PLS-DA methods determined the optimal number of wavelengths N to be 5 and 26, respectively. When evaluated on the independent external validation set, the SDPC-WSP-kNN model demonstrated better robustness, achieving sensitivity, specificity, and total recognition accuracy rates of 96.6%, 100%, and 98.7%, respectively. By introducing a grey judgment zone, both SEN and SPE reached 100%, with a detection recovery rate of 96.8%.

Conclusion: These results indicated that Vis-NIR spectroscopy pattern recognition can accurately discriminate between OBI and normal controls' plasma samples. This method is reagent-free, rapid, and simple, making it suitable for large-scale, low-cost rapid screening of OBI. In particular, the proposed few-wavelength model can provide an important reference for the development of small specialized blood analyzers for OBI detection.

Objective: This study aimed to investigate the association between lumbar lordosis (LL) and the sagittal hip-knee-ankle angle (sHKA) in patients with knee osteoarthritis (KOA) and to quantify the mediating effect of the sacral slope (SS).

Methods: This study enrolled 507 participants (left-side 302, right-side 205). Lateral full-length X-ray films of the lower extremities in weight-bearing position were collected from the research participants to measure radiological parameters such as lumbar lordosis (LL), sacral slope (SS), and sagittal hip-knee-ankle angle (sHKA), and SF-12 (12-items Short Form Health Survey) and WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) scores were also collected. Correlation analysis and Bootstrap mediation effect analysis were performed.

Results: Among the 507 KOA participants, LL was positively correlated with SS, HKA, sHKA, and SF-12 scores, and negatively correlated with JLCA and WOMAC scores. The mediation analysis revealed that SS accounted for 10.74% of the total association of LL on sHKA.

Conclusion: In patients with KOA, LL is closely related to sHKA, and this statistical association may be partially mediated by SS. This highlights the importance of adopting a "spine-pelvis-knee" perspective when assessing and treating KOA.

Bacterial secretion systems (SSs) are increasingly recognized as biological nanopores with potential biotechnological applications. Here, we engineered the transmembrane β-barrel of a trimeric autotransporter adhesin (TAA) secreted by the type Vc SS. The coiled-coil segment that occupies the central lumen of the transmembrane β-barrel of an Acinetobacter TAA, AtaA, was removed to design an open β-barrel pore, termed AtaApore. Polypeptides of AtaApore were produced using a cell-free expression system and reconstituted into lipid membranes. Electrophysiological measurements showed ion channel activity of AtaApore with a median conductance of 0.17 nS. Molecular dynamics simulations revealed ion transport properties, including transient trapping of Cl^- ions at a constriction formed by R3597 and R3622. Together, to our knowledge, these results provide the first characterization of a nanopore derived from a TAA secreted by the type Vc SS. AtaApore provides a new scaffold for nanopore engineering and a simplified model for probing the mechanism of the type Vc SS.