Frontiers in Bioengineering and Biotechnology最新文献

Total joint arthroplasty consistently alleviates pain and improves function in patients with end-stage joint disease. Nevertheless, up to 10% of hip and 20% of knee recipients remain dissatisfied after surgery, and registry data indicate that approximately one in five implants requires revision within 25 years, most commonly due to aseptic loosening, mechanical instability, or periprosthetic joint infection. Conventional postoperative surveillance relies on intermittent clinic visits and imaging, leaving a critical blind spot in our understanding of implant performance during daily activities. To address this gap, research has turned to fully implantable smart prostheses, such as hip and knee implants, embedded with sensors and low-power wireless telemetry that enable real-time monitoring of in vivo conditions. This review traces the evolution from early instrumented prototypes to the first commercially available smart knee; outlines enabling technologies, including sensing, communication, powering, and system integration; and summarizes clinical applications and early human data across this development continuum. Smart implants capture objective in vivo parameters that are not accessible to routine follow-up, including joint loads, range of motion, spatiotemporal gait metrics, and temperature, thereby enabling orthopedic phenotyping through dynamic, longitudinal digital representations of recovery trajectories and complication patterns. Fully implantable smart prostheses have the potential to shift arthroplasty toward continuous remote monitoring and proactive, precision follow-up care. Coupled with robust clinical decision-support systems and rigorous long-term evaluation, these technologies may usher in a new era of intelligent joint arthroplasty, with the potential to improve outcomes and extend implant longevity.

Burn injuries constitute a significant global health concern, presenting both health hazards and economic challenges. Recently, human adipose-derived mesenchymal stem cell exosomes (hADSCs-Exo) have emerged as a cell-free therapeutic strategy for promoting burn wound healing. These nano-sized particles function through various mechanisms, including promoting cellular migration, angiogenesis, inflammation reduction, immune response modulation, collagen remodeling, and scar prevention. They exert these effects by activating critical signaling pathways such as PI3K/Akt, IL-17RA/Smad, and mTOR. This review summarizes the biological characteristics and research relevance of hADSCs-Exo in burn injury management and discusses their translational implications.

Mannan oligosaccharides (MOS) are high-value prebiotics widely applied in the food, feed, and pharmaceutical industries. Mannanase, as the key rate-limiting enzyme in the biosynthesis of MOS, directly determines MOS yield and production cost based on its expression level. However, current industrial enzyme sources commonly exhibit low expression levels, poor secretion efficiency, and inadequate stability, severely limiting the reliable production of high-performance enzyme preparations. To overcome this core bottleneck, this study employed Aspergillus niger-an established industrial host-as the chassis organism and systematically improved the expression level and extracellular secretion efficiency of mannanase through integrated multi-dimensional strategies, including gene copy number regulation, secretion pathway optimization, and signal peptide modification. This project aims to provide efficient enzyme resources and robust technical support for the cost-effective and scalable biosynthesis of MOS. Specifically, Doubling the gene copy number enhanced man transcript levels 92.00% and extracellular mannanase activity by 66.25%, while tripling the copy number induced the unfolded protein response (UPR) and impaired growth. Deletion of AsAA relieved secretion stress, leading to a 10.11% increase in transcription and a 175.64% improvement in enzyme activity. Similarly, deleting Vps10 resulted in a 24.48% increase in transcription and a 30.08% increase in enzyme activity, likely by reducing degradation of folded protein. Replacement of the SglaA signal peptide with SpepB resulted in a 7.29% increase in transcript abundance and a 15.41% increase in enzyme activity. RT-qPCR analysis confirmed upregulation of several UPR-related genes (hacA, bipA, and pdiA) in most strains, consistent with ER stress under high expression burdens. The recombinant mannanase demonstrated high hydrolytic activity against konjac powder, yielding a total MOS content of 94.47% in the hydrolysis products, which highlights its significant potential for the efficient production of functional oligosaccharides. This study not only provides essential technical support for the industrial-scale synthesis of MOS, but also establishes a scalable engineering framework for the efficient heterologous expression of industrial enzymes.

Objective: To investigate the correlation between the activation status of quadriceps muscle and the proprioceptive accuracy in patients with knee osteoarthritis (KOA).

Methods: We included 43 outpatients diagnosed with KOA and 45 health subjects from October 2024 to May 2025. The correlation between the absolute error in knee Joint Position Reproduction (JPR) and the root mean square (RMS) and median frequency (MDF) of quadriceps surface electromyography during walking and stair climbing was analyzed.

Results: The JPR of 45° in KOA patient is significantly higher than health subjects. There was no significant difference in 30° and 60° JRP between the two groups. While walking, there is no significant difference of the sEMG data in two group. While going up stair, the RMS of LVM and RVM in KOA group had increased activation compared with the health subjects. In KOA group, while going up stair, the JPR absolute error angle of 30° was negatively correlated with the MDF of RVL, the JPR absolute error angle of 45° was positively correlated with the RMS of RVM, and the JPR absolute error angle of 60° was positively correlated with RMS of LVM and RVM. There are no significantly correlation in JPR absolute error angle and the surface electromyography of the quadriceps muscle while walking and in health control group. Partial correlation analysis was performed on the aforementioned correlated indicators with gender included as a control variable, and the results indicated that in women group, the JPR absolute error angle of 60° was positively correlated with RMS of LVM and RVM. In KOA group, the RMS of LVL, RVL and RVM in walking was positively correlated with the RMS of LVL, RVL and RVM in going up and down stair, and the MDF of LVL, RVL and RVM in walking was positively correlated with the MDF of LVL, RVL and RVM in going up and down stair. In health control group, the MDF of LVL, RVL and RVM in walking was positively correlated with the MDF of LVL, RVL and RVM in going up and down stair.

Conclusion: This study indicated that during stair climb, KOA patients display a unique pattern of elevated RMS of the VM. Notable relationships were identified between the absolute error angles of JPR and sEMG parameters of VM. The pronounced positive correlations in muscle activation patterns between walking and stair upward and downward activities indicate a fixed, task-invariant neuromuscular approach in KOA patients, possibly resulting from compromised sensorimotor integration due to proprioceptive impairments. These findings offer new insights into the pathogenesis of KOA from a neuromuscular-sensory viewpoint, emphasizing the need for future rehabilitation therapies to concurrently target proprioceptive accuracy and the enhancement of muscle activation patterns.

Host cell proteins (HCPs) are major process-related impurities in biopharmaceutical manufacturing, imposing metabolic burden on production hosts and complicating downstream purification, thereby impacting cost, product stability, and patient safety. Here, we engineered Chinese hamster ovary (CHO) cells toward a streamlined production chassis through multiplex CRISPR-mediated knockout of abundant and difficult-to-remove HCPs. Proteomic profiling across multiple clones, products, and downstream purification steps identified a core set of highly abundant proteins that contributed disproportionately to total released HCP mass and showed limited removal by standard purification processes. Screening of 62 candidate genes using pooled and single-cell knockout approaches identified targets compatible with cell growth and productivity, yielding 36 validated candidates suitable for host-cell streamlining. Multiplex editing of selected targets achieved approximately 57-85% reduction in released HCP levels, depending on configuration, without compromising growth, viability, or productivity in fed-batch cultures. The resulting cell lines maintained bioprocess performance while substantially lowering impurity load. Together, this work demonstrates a scalable, proteomics-guided strategy for rational host-cell engineering that enables upstream reduction of persistent impurities and supports cleaner, safer, and more cost-efficient biopharmaceutical manufacturing.

Objectives: Intervertebral disc degeneration (IVDD) is a major contributor to chronic low back pain and disability worldwide, yet current treatments remain largely palliative and do not restore disc structure or biomechanical integrity. Stem cell-derived extracellular vesicles (SC-sEVs) have emerged as promising cell-free biologics capable of modulating inflammation, apoptosis, and extracellular matrix homeostasis.

Methods: This systematic review and meta-analysis evaluated the therapeutic efficacy of SC-sEVs in rat models of puncture-induced IVDD, with a specific focus on comparing hydrogel-assisted versus direct (non-hydrogel) delivery strategies. The review was prospectively registered in PROSPERO (CRD420250654980) and conducted according to PRISMA 2020 guidelines.

Results: Comprehensive searches of PubMed, Embase, and the Cochrane Library through August 2025 identified 19 studies enrolling 305 rats. Extracted outcomes included disc height index (DHI), MRI Pfirrmann grade, and histological score. Meta-analysis demonstrated significant improvements in DHI (mean difference [MD] = 12.8%, 95% CI 7.6-18.0), histological grade (MD = -4.1, 95% CI -5.1 to -3.2), and MRI Pfirrmann grade (MD = -1.5, 95% CI -1.8 to -1.2) at 4-8 weeks following treatment. Hydrogel-assisted delivery produced comparable overall efficacy to direct injection but contributed to reduced interstudy heterogeneity. Both human- and rat-derived EVs significantly improved all evaluated outcomes, with human-source EVs showing a modest advantage in MRI grading (P = 0.017). Risk-of-bias assessment indicated generally acceptable methodological quality, and no substantial publication bias was observed.

Conclusion: Overall, SC-sEV therapy demonstrates consistent regenerative benefits in preclinical IVDD models, supporting its translational promise as a minimally immunogenic, cell-free therapeutic for degenerative spine disorders. Future studies employing standardized protocols, mechanistic analyses, and long-term evaluation are needed to facilitate clinical translation.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420250654980, identifier CRD420250654980.

Objectives: Reverse Potts shunt is a promising yet high-risk therapy for pediatric pulmonary arterial hypertension. Postoperative hemodynamics is critically influenced by shunt configuration but is difficult to predict. This study aimed to quantify the effects of shunt size and location on hemodynamics to guide surgical planning.

Methods: Based on a patient-specific model, four postoperative models with two different shunt locations [left pulmonary artery (LPA)-descending aorta (DAO) and pulmonary artery bifurcation-aortic arch] and three conduit sizes (4, 5, and 6 mm) were created. The direct Potts shunt model was created by a direct side-to-side anastomosis between the LPA and DAO with a 6-mm circular opening. Quantitative parameters including the shunt ratio (SR), which was defined as the percentage of the shunt flow rates to the total pulmonary inflow rate, lower limb oxygen saturation, and pressure were analyzed.

Results: Increasing the shunt size from 4 mm to 6 mm elevated the SR from 6.01% to 9.80%, concurrently reducing lower limb oxygen saturation from 89.57% to 86.52%. When taking 11,000 Pa as the threshold, this increased SR resulted in a reduction of the high-pressure area from 17.32% of the total pulmonary artery area to almost zero. Meanwhile, the high-pressure area on the aorta expanded from 8.72% of the total aortic area to 14.94%. These results indicated a reduction in the right ventricular afterload and an increase in the left ventricular afterload. Notably, a 6-mm shunt at the pulmonary artery bifurcation yielded a significantly larger SR than at the LPA (9.80% vs. 2.68%), which is attributed to a higher pressure gradient at the pulmonary artery bifurcation (1,201 Pa vs. 162 Pa).

Conclusion: The shunt location had a greater impact on the SR than shunt size within the 4 mm-6 mm range in this specific case. A 6-mm shunt at the pulmonary artery bifurcation yielded a significantly larger SR than at the LPA, which is attributed to the higher preoperative pressure gradient at the bifurcation site. Left heart function is as critical as right heart function in maintaining pressure balance and determining outcomes, as the shunt flow increases the left ventricular afterload.

Background: Revision surgery for femoral nonunion is technically challenging, and there is limited evidence supporting effective treatments for cases with multiple failed revisions. This study aims to evaluate the efficacy of platelet-rich plasma-enhanced "plum blossom" bone grafting combined with a bioactive chamber in treating refractory femoral nonunion after multiple failed revisions.

Methods: A retrospective analysis was conducted on patients with refractory femoral nonunion treated at a high-level trauma center between January 2021 and July 2024. These patients underwent mechanical optimization, platelet-rich plasma -enhanced "plum blossom" autologous iliac bone grafting, and bioactive chamber therapy. Radiographic outcomes included union rate and limb shortening, while clinical outcomes encompassed healing time, visual analog scale pain score, SF-36 quality of life score, Harris hip score, and complications.

Results: Thirty-three patients were included (24 males, 9 females), with a mean age of 42.64 ± 13.03 years. The average number of previous surgeries was 2.64 ± 1.17. The nonunion types were hypertrophic (4 cases, 12.10%), atrophic (24 cases, 72.70%), and oligotrophic (5 cases, 15.20%). The mean bone defect was 3.87 ± 1.05 cm, and the mean follow-up duration was 16.06 ± 3.37 months. The union rate was 96.97% (32/33), with a mean healing time of 9.78 ± 1.75 months. Post-treatment, significant improvements were observed in VAS score (4.27 ± 1.18 vs. 1.21 ± 1.05, p < 0.001), Harris hip score (50.91 ± 8.47 vs. 86.39 ± 7.75, p < 0.001), SF-36 score (59.21 ± 5.63 vs. 84.48 ± 5.32, p < 0.001), and limb shortening (2.20 ± 0.64 vs. 0.32 ± 0.57, p < 0.001). Two patients (6.06%) experienced severe complications (1 case of persistent nonunion, 1 case of deep vein thrombosis).

Conclusion: The synergistic effect of biomechanical stability and biological stimulation is a critical pathway to overcoming traditional treatment limitations. This study provides a reference method for managing refractory and recalcitrant femoral nonunion.

Objective: To employ shear wave elastography (SWE) to assess changes in stiffness and reliability in the vastus rectus muscle of healthy adults across different posture-contraction states. We analyzed the main effects and interactions of posture and contraction intensity on shear wave velocity (SWV) and explored its relationship with relevant biological parameters.

Methods: We recruited healthy participants, with two observers using SWE technology to measure the SWV of the vastus rectus muscle in the supine (relaxation, plantarflexion, and dorsiflexion) and sitting (relaxation, leg elevated, and 5-kg loading) positions. Intra- and interobserver reliabilities were evaluated using the intraclass correlation reliability. Repeated-measures analysis of variance was used to examine the main effects and interactions of posture and contraction state on SWV. Additionally, correlations between the SWV and rectus femoris thickness (RF_thick), circumference (RF_circ), cross-sectional area (RF_csa), and contraction index (RF_ci) were calculated.

Results: Forty-six adults (11 males and 35 females) completed the study. SWE measurements demonstrated high intra- and interobserver reliability across all conditions (ICC >0.80). Two-way repeated-measures analysis of variance revealed significant main effects of body position (F (1,45) = 58.85, P < 0.001, η_p ² = 0.567) and contraction state (F (1.76, 78.97) = 104.23, P < 0.001, η_p ² = 0.777), with a significant interaction (F (2,44) = 24.66, P < 0.001, η_p ² = 0.459). The SWV changes were more pronounced in the 5-kg load position (45.9%). Ultrasound parameters (RF_thick, RF_circ, RF_ci) varied significantly across conditions (P < 0.05), whereas the RF_csa did not (P = 0.194). The SWV was positively correlated with specific architectural parameters, depending on posture, but not with demographic variables (P > 0.05).

Conclusion: This study establishes a methodological basis for assessing the stiffness of the RF, identifying posture and contraction as key factors. Our findings underscore the need for standardized measurement and support the future application of SWE in biomechanics, sports, and rehabilitation.