Frontiers in Bioengineering and Biotechnology最新文献

Objective: Screw loosening is a common complication following lumbar spine fixation surgery, yet the biomechanical outcomes after screw loosening remain rarely reported. This study aims to utilize finite element (FE) models to compare the biomechanical performance of PEEK rod dynamic fixation and titanium rod rigid fixation in the postoperative lumbar spine, exploring potential biomechanical mechanisms for re-stabilization of loosened screws.

Methods: A FE model of the lumbar spine from L3 to the sacrum was developed using CT image segmentation. Four L4-S1 fixation models were constructed: PEEK rod dynamic fixation (PEEK model), titanium rod rigid fixation (titanium model), PEEK rod with pedicle screw loosening (PEEK-PSL model), and titanium rod with pedicle screw loosening (titanium -PSL model). A preload of 300 N was applied to the superior surface of L3. Stress distributions in the intervertebral discs, facet joints, pedicle screws, and rods were calculated to evaluate the biomechanical effects of different fixation methods.

Results: Across four physiological loading conditions, the stress differences in intervertebral discs, facet joints, and nucleus pulposus between the PEEK model and titanium model were minimal. However, vertebral body stress was significantly higher in the PEEK model, whereas screw and rod stresses were greater in the titanium model. Screw loosening further increased stress in all models. The S1 screw in the PEEK-PSL model exhibited lower and more uniform stress, while stress was concentrated at the screw-rod junction in the titanium-PSL model.

Conclusion: The PEEK rod fixation system demonstrated superior stress distribution, reducing stress concentration risks and improving stability while minimizing screw loosening rates. In contrast, the titanium rod system offers advantages in scenarios requiring high rigidity, potentially making it more suitable for patients with greater stability needs.

Objective: This study aimed to evaluate the effectiveness of bone marrow mesenchymal stem cells (BMSCs) combined with sodium alginate scaffolds in repairing knee cartilage defects in New Zealand rabbits. Additionally, it assessed the potential of functional magnetic resonance imaging (fMRI) for non-invasive monitoring of the dynamic repair process.

Methods: Rabbits were randomly divided into four groups: Group A (control), Group B (sodium alginate scaffold), Group C (BMSCs-sodium alginate scaffold), and Group D (USPIO-labeled BMSCs-sodium alginate scaffold). A cartilage defect model was created, and the respective materials were implanted into the defect regions. T2 mapping MRI was performed at weeks 1, 2, and 4 post-surgery to evaluate the repair process, followed by histological analysis to confirm the outcomes.

Results: BMSCs significantly promoted cartilage defect repair and accelerated the degradation of sodium alginate scaffolds. Macroscopic and histological evaluations revealed repair tissue formation in Groups C and D by week 1, with most defect regions filled with new cartilage by week 4. T2 mapping analysis showed a gradual decline in T2 values in Group B, a more pronounced decrease in Group C, and consistently lower T2 values in Group D compared to Group C, with a slow upward trend over time.

Conclusion: This study demonstrated that BMSCs exhibit significant regenerative potential for cartilage defect repair. USPIO labeling enables non-invasive, dynamic monitoring of the repair process without adverse effects on cell viability or differentiation. These findings provide experimental evidence supporting the application of BMSCs combined with magnetic labeling technology in cartilage regeneration.

Active lower-body exoskeleton devices can decrease the energy requirement of the human body by providing mechanical assistance to lower-body muscles. However, they also alter gait kinematics and kinetics, and it is not well understood whether such alterations are detrimental or beneficial to the human body. In this pilot study, we investigated the impact of walking with an ankle exoskeleton device on the biomechanics of men while carrying a heavy load. We collected computed tomography images and motion-capture data for five young, healthy men who walked 5 km (∼60 min) with a 22.7-kg load, with and without an active ankle exoskeleton (the ExoBoot EB60). We developed personalized musculoskeletal models and calculated the joint kinematics and kinetics for each participant under each walking condition. Without the ExoBoot, at 5 km compared to 0 km, on average, the peak trunk flexion angle increased by ∼35% and the stride length increased by ∼3.5%. In contrast, with the ExoBoot, the magnitude of the corresponding increases was smaller (∼16% and ∼2%, respectively). After the 5-km walk, compared to walking without the ExoBoot, its use considerably altered hip-related biomechanical parameters, e.g., it increased hip abduction angle by ∼17%, increased hip flexion moment by ∼3.5%, and decreased hip adduction moment by ∼19%. Finally, irrespective of distance, ExoBoot use significantly increased the stance duration and peak ankle plantarflexion angle (p < 0.001). Overall, the use of the ExoBoot induced beneficial alterations in stride length and trunk-, ankle-, and hip-related parameters for men walking with load carriage. The quantitative analysis provided by this pilot study should help guide future investigations and inform the development of standards for safe and effective use of emerging exoskeleton technologies.

Liver cancer, a highly aggressive malignancy, continues to present significant challenges in therapeutic management due to its pronounced chemoresistance. This resistance, which undermines the efficacy of conventional chemotherapy and targeted therapies, is driven by multifaceted mechanisms, with increasing emphasis placed on the protective role of the tumor microenvironment (TME). The hepatocellular carcinoma extracellular matrix (ECM), a primary non-cellular component of the TME, has emerged as a critical regulator in cancer progression and drug resistance, particularly in hepatocellular carcinoma cell (HCC). In this study, a hybrid biomimetic hydrogel was engineered by integrating decellularized hepatocellular carcinoma matrix (DHCM) with gelatin methacrylate (GelMA) precursors. This composite DHCM/GelMA hydrogel was designed to replicate the physicochemical and functional properties of the hepatocellular carcinoma ECM, thereby offering a biomimetic platform to explore the interactions between HCCs and their microenvironment. Leveraging a custom-designed microfluidic 3D printing platform, we achieved high-throughput fabrication of HCC-encapsulated DHCM/GelMA microgels, characterized by enhanced uniformity, biocompatibility, and scalability. These microgels facilitated the construction of hepatocellular carcinoma microtissues, which were subsequently employed for chemoresistance studies. Our findings revealed that DHCM/GelMA microgels closely mimic the hepatocellular carcinoma tumor microenvironment, effectively recapitulating key features of ECM-mediated drug resistance. Mechanistic studies further demonstrated that DHCM significantly upregulates the expression of Aquaporin 3 (AQP3) in the encapsulated HCCs. This upregulation potentially activates mTOR signaling-associated autophagy pathways, thereby enhancing chemoresistance in HCCs. These biomimetic models provide a robust and versatile platform for studying the underlying mechanisms of drug resistance and evaluating therapeutic interventions. This innovative approach highlights the potential of DHCM/GelMA microgels as a transformative tool in cancer-associated tissue engineering and anticancer drug screening. By enabling detailed investigations into the role of ECM in chemoresistance, this study contributes to advancing therapeutic research and offers promising strategies to overcome drug resistance, ultimately improving clinical outcomes in liver cancer treatment.

Mitochondria play a significant role in several cellular activities and their function in health and disease has become an important area of research. Since the brain is a high-energy-demanding organ, it is particularly vulnerable to mitochondrial dysfunction. This has been implicated in several brain disorders including neurodegenerative, psychiatric and neurological disorders, e.g., Parkinson's disease and schizophrenia. Significant efforts are underway to develop mitochondria-targeting pharmaceutical interventions. However, the complex mitochondrial membrane network restricts the entry of therapeutic compounds into the mitochondrial matrix. Nanoparticles (NPs) present a novel solution to this limitation, while also increasing the stability of the therapeutic moieties and improving their bioavailability. This article provides a detailed overview of studies that have investigated the treatment of mitochondrial dysfunction in brain disorders using either targeted or non-targeted NPs as drug delivery systems. All the NPs showed improved mitochondrial functioning including a reduction in reactive oxygen species (ROS) production, an improvement in overall mitochondrial respiration and a reversal of toxin-induced mitochondrial damage. However, the mitochondrial-targeted NPs showed an advantage over the non-targeted NPs as they were able to improve or rescue mitochondrial dynamics and biogenesis, and they required a lower concentration of the in vivo therapeutic dosage of the drug load to show an effect. Consequently, mitochondria-targeted NPs are a promising therapeutic approach. Future studies should exploit advances in nanotechnology, neuroscience and chemistry to design NPs that can cross the blood-brain barrier and selectively target dysfunctional mitochondria, to improve treatment outcomes.

Background and aims: Hybrid atrial fibrillation (AF) ablation is a therapeutic option in non-paroxysmal AF. Our study examines cardiac mechanics changes after hybrid AF ablation plus epicardial closure of left atrial appendage (LAA).

Methods: All consecutive patients undergoing hybrid AF ablation at UZ Brussel were evaluated. They received pulmonary vein isolation (PVI), posterior wall isolation (LAPWI), and epicardial LAA closure. Left atrium (LA) and Left ventricle (LV) mechanics were analyzed, with the following measures obtained at baseline, post-ablation, and follow-up: 1) volumes (EDV, ESV); 2) ejection fraction (EF); 3) strain (ENDO GCS, ENDO GLS); 4) forces (LVLF, LVsysLF, LVim, LVs).

Results: A total of 50 patients were included. At follow-up, LAEDV decreased from baseline [44.7 mL vs 53.8 mL, P = 0.025]. LA ENDO GCS and GLS increased post-ablation, with further GLS improvement at follow-up. LV ENDO GCS and LV ENDO GLS also rose post-ablation [-26.7% vs. -22.5%, P < 0.001] and [-20.57% vs. -16.6%, P < 0.001], respectively. LVEF increased post-ablation [54.6% vs 46.3%, P < 0.001]. There was an increase in all LV hemodynamic forces (HDFs) and in particular: LVLF and LVsysLF increased post-ablation [15.5% vs 10.4%, P < 0.001] and [21.5% vs 14.11%, P < 0.001], respectively. LVim also increased post-ablation [19.6% vs 12.8%, P < 0.001]. Finally, there was an increase in LVs post-ablation compared to baseline [10.6% vs 5.4%, P < 0.001].

Conclusion: In patients undergoing hybrid AF ablation, there was a significant and persistent improvement in the mechanical and hemodynamic functions of both LA and LV.

Iron is essential for vital cellular processes, including DNA synthesis, repair, and proliferation, necessitating enhanced iron uptake and intracellular accumulation. Tumor cells, in particular, exhibit a pronounced elevation in iron uptake to sustain their continuous proliferation, migration and invasion. This elevated iron acquisition is facilitated predominantly through the upregulation of transferrin receptors, which are closely associated with tumorigenesis and tumor progression. Incorporating transferrin into drug delivery systems has been shown to enhance cytotoxic effects in drug-sensitive cancer cells, offering a potential method to surpass the limitations of current cancer therapies. Intracellular iron predominantly exists as ferritin heavy chain (FTH), ferritin light chain (FTL), and labile iron pool (LIP). The innovation of nanocarriers incorporating iron chelating agents has attracted considerable interest. Iron chelators such as Deferoxamine (DFO), Deferasirox (DFX), and Dp44mT have demonstrated significant promise in cancer treatment by inducing iron deficiency within tumor cells. This review explores recent advancements in nanotechnology aimed at targeting iron metabolism in cancer cells and discusses their potential applications in cancer treatment strategies.

Introduction: Skin aging is an inevitable physiological process driven by factors like cellular senescence, ultraviolet radiation (UV) radiation, and environmental pollutants. A key feature is the accelerated collagen degradation in the dermal extracellular matrix, leading to visible signs such as sagging, wrinkles, and hyperpigmentation. Traditional fillers, such as hyaluronic acid and collagen-based fillers, offer only temporary volume enhancement without stimulating collagen regeneration. Studies have shown that electrical signals generated by piezoelectric materials can promote tissue regeneration.

Methods: This study explored the potential of piezoelectric PHBHHx microspheres as an innovative skin filler for enhancing collagen regeneration and improving maxillofacial aesthetics, with the aid of low-intensity pulsed ultrasound (LIPUS) stimulation. A comprehensive characterizations of the piezoelectric PHBHHx microspheres were conducted, and their potential to stimulate collagen regeneration was assessed using a subcutaneous injection model in New Zealand white rabbits.

Results: The results indicated that PHBHHx microspheres exhibited stable degradation properties, great piezoelectric properties and excellent biocompatibility. Moreover, when stimulated by LIPUS, the collagen-regenerating effect of PHBHHx microspheres was further enhanced, histological analysis revealed a denser and more organized collagen structures in LIPUS-stimulated PHBHHx group.

Discussion: These findings highlight the potential of PHBHHx microspheres as an advanced biomaterial for applications in aesthetic medicine, particularly in promoting collagen regeneration and enhancing skin rejuvenation.

The process of tendon-to-bone healing is regulated by several proteins and cytokines that play critical roles in shaping biomechanical properties and functional recovery. Among these, the ubiquitin-like protein ISG-15 has been reported to have a beneficial effect on tissue repair. However, its specific function in tendon-to-bone interface regeneration has not been well characterized. This study investigated the function of ISG15 in vitro and addressed its in vivo effects on tendon and bone healing. In this study, wild-type C57/BL6 mice underwent anterior cruciate ligament (ACL) reconstruction surgery, with a sustained-release hydrogel containing ISG15 protein injected into the bone tunnels in the treatment group. To assess its therapeutic potential, bone-tendon interface growth was evaluated through histological staining, while micro-computed tomography (Micro-CT) was employed to quantify newly formed bone and bone density within the bone tunnels. Additionally, biomechanical testing was performed to measure the mechanical strength of the grafted tendons, and immunohistochemistry was conducted to detect the expression of Runx2 and osteocalcin (OCN) at the bone-tendon interface. In vitro results showed that an appropriate concentration of ISG-15 has the ability to promote osteogenic differentiation of bone marrow mesenchymal stem cells. Also, In the in vivo experiments, the local application of ISG15 protein significantly reduced inflammatory tissue growth during the early stages of healing and minimized bone resorption in the later stages. Furthermore, Micro-CT analysis showed an increased volume of newly formed bone in the treatment group, while biomechanical testing demonstrated enhanced mechanical strength of the grafted tendons. In summary, this study suggests that the localized sustained release of ISG15 protein during ACL reconstruction facilitates tendon-to-bone interface repair by promoting bone ingrowth, ultimately leading to improved biomechanical properties and functional recovery.