Frontiers in Bioengineering and Biotechnology最新文献

Introduction: Chronic wounds related to diabetes incur significant morbidity and mortality, yet few effective therapies are available. Although whole body low-intensity vibration (LIV) has been shown to improve angiogenesis and wound healing in diabetic mice, local application of LIV signals could enhance the utility of this therapeutic approach.

Methods: The purpose of the present study was to compare the effectiveness of different treatment regimens involving local LIV applied to wounds of diabetic mice via oscillating motor, or by a wearable piezoelectric device.

Results: Local LIV delivered by oscillating motor enhanced angiogenesis, granulation tissue formation and wound closure to a similar degree for all vibration protocols tested. In addition, local LIV induced protocol-dependent increases in wound IGF1 and VEGF levels that did not necessarily correlate with the effects on healing. LIV delivered by piezoelectric disks involved accelerations that were an order of magnitude smaller than those delivered by the oscillating motor, but produced significant increases in angiogenesis and granulation tissue formation, with trends of enhanced wound closure. These changes were associated with increased VEGF but not IGF1 levels.

Discussion: These findings demonstrate that local delivery of LIV can enhance key aspects of diabetic wound healing, highlighting its potential as a non-invasive method for improving healing of chronic diabetic wounds.

Introduction: Steroid-induced osteonecrosis of the femoral head (SONFH) is a progressive and debilitating disorder caused by excessive glucocorticoid exposure. Dysfunction of bone marrow mesenchymal stem cells (BMSCs) and their exosome (Exos)-mediated signal transduction plays a key role in SONFH; however, the exact pathways involved remain under active investigation.

Methods: The differential expression profiles of long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) related to the Exos-mediated pathway in Exos derived from human BMSCs (hBMSCs) of patients with SONFH and control patients were analyzed by next-generation sequencing (NGS). The miR-199a-3p was identified as a differentially expressed miRNA, and its expression in BMSCs and their corresponding Exos was subsequently validated using quantitative real-time polymerase chain reaction. A series of functional experiments then confirmed that miR-199a-3p modulated osteoblasts (OBs) and human umbilical vein endothelial cells (HUVECs) activities via the Exos-mediated pathway, including cell proliferation, apoptosis, osteogenesis, and angiogenesis, with or without exposure to high-dose dexamethasone (Dex).

Results: NGS results revealed a total of 6,953 differentially expressed ncRNAs, 260 differentially expressed miRNAs, 13,577 differentially expressed mRNAs were identified in hBMSCs from patients with SONFH compared to controls. In hBMSCs-Exos, 207 differentially expressed ncRNAs, 183 differentially expressed miRNAs, and 1,075 differentially expressed mRNAs were detected. Integrated analysis of transcripts expressed in both hBMSCs and hBMSCs-Exos identified 659 differentially expressed ncRNAs, 11 differentially expressed miRNAs, and 1,600 differentially expressed mRNAs. The results of bioinformatics analysis showed that these differentially expressed RNAs were involved in regulation of endocytosis, receptor-mediated endocytosis, response to extracellular stimuli, and bone mineralization. Furthermore, the validation results demonstrated that the suppression of miR-199a-3p promoted proliferation, osteogenesis, and angiogenesis, while inhibiting apoptosis of OBs and HUVECs activities and exposed to high-dose Dex.

Discussion: This study identified differential expression profiles of ncRNAs, miRNAs and mRNAs related to the Exos-mediated pathway in SONFH through integrated analysis, and further demonstrated the negative role of miR-199a-3p in SONFH, involving proliferation, osteogenesis, and angiogenesis, as well as the regulation of apoptosis of OBs and HUVECs exposed to high-dose Dex through the hBMSCs-Exos-mediated pathway. Therefore, targeting miR-199a-3p may enhance the therapeutic efficacy of Exos-based treatments for SONFH.

Globally, esophageal cancer (EC) is the seventh most commonly diagnosed cancer and the sixth leading cause of cancer-related death. However, its treatment remains challenging due to significant obstacles. Photothermal therapy (PTT), a minimally invasive technique, has emerged as a promising method for tumor ablation. However, its efficacy is limited by low photothermal conversion efficiency and poor tissue penetration. To address these limitations, this study developed a metal-organic framework (MOF)-based nanozyme for the treatment of EC. In this system, the dye IR780, used for photothermal conversion, was encapsulated in liposomes and anchored onto the MOF nanozyme, resulting in a Pt@MOF@PSs construct that improved the aqueous stability of IR780. This multifunctional nanozyme showed tumor-targeting and synergistic therapeutic effects. After passive accumulation in EC tissues, Pt@MOF@PSs suppressed hypoxia and promoted reactive oxygen species (ROS) production by using the high H₂O₂ levels typical of the tumor microenvironment. The PTT activity of Pt@MOF@PSs was confirmed by its significant temperature increase and upregulation of heat shock protein 70 after irradiation with an 808 nm near-infrared laser. These features facilitated the effective modulation of the resistant tumor microenvironment, induced localized hyperthermia, exerted potent cytotoxicity against esophageal squamous carcinoma cells (ESCs), and suppressed EB tumor progression. These findings highlight Pt@MOF@PSs as a promising therapeutic option, integrating hypoxia relief, ROS generation, and PTT for improved therapeutics against EC.

Background: 3D printing enables the fabrication of customized breast phantoms for image quality assessment in digital mammography (DM) and digital breast tomosynthesis (DBT). A major challenge is the absence of standardized, accessible methods to characterize the attenuation properties of 3D-printed materials under clinical DM/DBT spectra.

Methods: An experimental framework was implemented to determine the effective X-ray attenuation coefficient (μ _eff ) of six 3D-printed polymers (PLA, PET, resin, ABS, ABS+, HIPS) and reference breast tissue-equivalent materials (CIRS plates simulating different breast glandular/adipose ratios (BR) and PMMA) using two commercial DM/DBT systems, with and without anti-scatter grid. Step-wedges (0.5-5.5 cm) were imaged across multiple kVp and filter settings. The μ _eff were obtained from measurements on images and fitted to an empirical model yielding μ ₀ (attenuation at thickness tending to zero) and k (decay rate) to characterize beam hardening and scatter influences. 3D-reference material equivalences were evaluated based on μ _eff and μ ₀ .

Results: Beam hardening and scatter reduced μ _eff with thickness, by 6%-14% with grid and 12%-28% without grid, with scatter contributing 47%-76% of the reduction in no-grid acquisitions. No significant differences were observed between the two mammography systems. Based on μ _eff values, attenuation equivalences (within ±6%) were identified between 3D-printed and reference breast tissue-equivalent materials: PLA with BR 100/0; PET and resin with BR 70/30 and PMMA; ABS+ with BR 30/70 and BR 50/50. ABS and HIPS showed larger mismatches. The empirical model achieved excellent fits (R² > 0.99), with μ ₀ values preserving attenuation ranking and enabling derivation of equivalent glandular proportions.

Conclusion: This framework demonstrates that routine clinical mammography systems can be used directly, without specialized instrumentation, to characterize 3D-printed materials as tissue surrogates. Several low-cost, widely available polymers were shown to reproduce breast tissue attenuation, supporting the local fabrication of anthropomorphic breast phantoms for realistic and clinically relevant image quality evaluation.

The glenoid labrum is a fibrocartilaginous structure essential for shoulder stability, yet its regeneration remains an unmet clinical challenge. Current surgical approaches restore initial joint stability but frequently fail to reestablish native biomechanics, leading to recurrence and early degenerative changes. In this study, we investigated the feasibility of fabricating a patient-specific, anatomically scaled glenoid labrum scaffold using digital modeling based on magnetic resonance imaging and 3D cryo(bio)printing of a gelatin methacryloyl (GelMA) hydrogel. Printing was performed in a temperature-controlled platform (22.5 °C, 15 °C, and -20 °C) to evaluate the influence of thermal conditions on structural fidelity and biological performance. Quantitative analyses showed that cryogenic deposition markedly improved printing precision, reducing filament spreading and enhancing geometric accuracy in both sharp-angle and grid-pattern evaluations. Biological assays indicated high viability of human mesenchymal stem cells under all temperature conditions, validating the cytocompatibility of the methodology. Morphological assessment by structured-light 3D scanning demonstrated that bioprinted patient-specific scaffold at -20 °C achieved the highest correspondence to the digital reference model. Overall, the integration of anatomical modeling with cryo(bio)printing proved to be an effective approach for producing anatomically faithful, patient-tailored scaffolds. This study presents the first demonstration of human glenoid labrum bioprinting and establishes a foundation for future translational research in fibrocartilaginous tissue regeneration.

Due to their special molecular weight and pharmacokinetic/pharmacodynamic (PK/PD) characteristics, antibody drugs have difficulty crossing the body barrier and entering complex microenvironments to provide effective treatment for encephalopathy, cancer, and severe infectious diseases. With the development and application of nanotechnology, drugs can be modified by nanomethods to increase the delivery efficiency, targeting, and permeability, reduce the resistance to the antibody, and improve the response rate, thus increasing their safety and effectiveness. Therefore, nanoparticles have extensive research and application value in drug delivery systems. This article summarizes the characteristics of nanoparticles and nanoantibody delivery systems to provide a reference for the future application of nanoparticles in drug delivery.

Background: Adenoid hypertrophy (AH) is a leading cause of pediatric obstructive sleep apnea, yet first-line diagnostics are invasive or resource-intensive. We developed and externally tested a low-cost, noninvasive screening model that fuses quantitative voice features with routine clinical variables for pre-endoscopy and primary-care triage.

Methods: In a dual-center cross-sectional study (N = 202), Center 1 (Capital Center for Children's Health, Capital Medical University, n = 161) served as the development cohort and Center 2 (College of Otolaryngology Head and Neck Surgery, The 6th Medical Center, National Clinical Research Center for Otolaryngologic Diseases, Chinese PLA General Hospital, Beijing, China, n = 41) as the independent external cohort. Children produced sustained/a/phonations; Mel-frequency cepstral coefficients (MFCCs) were summarized into fixed statistics and combined with readily available clinical information. Modeling used patient-level aggregation with stratified 10-fold cross-validation in development. The final classifier was selected by a joint criterion of AUC and average precision (AP), then a single Youden-derived locked cutoff was determined in the development set and applied unchanged to the external cohort. Discrimination (AUC/AP), calibration (Brier score, slope, intercept), and clinical utility were evaluated.

Results: Internal performance was stable (AUC = 0.81; AP = 0.84). On the small external cohort, discrimination remained (AUC = 0.79; AP = 0.88). At the locked cutoff, the model achieved clinically actionable sensitivity/specificity with balanced F1. Calibration was acceptable (Brier = 0.20, slope = 0.71, intercept = 0.94). Decision-curve analysis showed positive net benefit across a wide range of threshold probabilities versus "treat-all" and "treat-none." SHAP explainability indicated MFCC variability-related features and a subset of airway-symptom clinical variables as leading contributors, aligning with hyponasal resonance changes in AH.

Conclusion: A patient-level model with a locked decision threshold showed preservation of discrimination in a small external cohort, supporting a practical pathway for noninvasive, low-overhead AH triage prior to nasoendoscopy. Prospective multicenter studies are warranted.

Introduction: Effective cryopreservation is essential for the clinical application and large-scale banking of mesenchymal stem cells (MSCs). This study compares the performance of a novel DMSO-free cryoprotectant, XT-Thrive®, with a conventional DMSO-based solution, CryoStor® CS10, in preserving both commercial and donor-derived bone marrow MSCs (BM-MSCs). Evaluations focused on viability, recovery, proliferation, and functional characteristics across master cell bank (MCB), working cell bank (WCB), and final product (FP) stages.

Methods: In Part 1, commercial BM-MSCs were cryopreserved in XT-Thrive or CS10 and evaluated for pre-freeze viability, post-thaw survival (up to 6 h), and recovery in 2D and 3D cultures. In Part 2, donor-derived BM-MSCs were cryopreserved at passages 2 (MCB), 4 (WCB), and 8 (FP), and assessed for cumulative population doubling levels (cPDL), immunophenotype, clonogenicity, differentiation potential, secretome profile, telomere length, karyotype stability, and tumorigenicity.

Results: XT-Thrive-preserved MSCs maintained >90% pre-freeze viability after 24-h room temperature holding, compared to a ∼40% drop with CS10. Post-thaw viability at 6 h remained above 85% with XT-Thrive, vs. 60%-70% with CS10. In 3D microcarrier cultures under serum-free conditions, XT-Thrive-preserved MSCs demonstrated a ∼2.5-fold improvement in viable cell recovery compared to CS10, which failed to support recovery and expansion. XT-Thrive-preserved donor MSCs showed significantly higher cPDL at passages 8 FP (19.8 ± 0.4 vs. 15.4 ± 0.5, p < 0.001). CFU-F efficiency was also higher (∼23% vs. ∼15%). Furthermore, XT-Thrive-preserved MSCs exhibited enhanced osteogenic differentiation and increased secretion of FGF2 and HGF (1.8-fold and 2.1-fold increase, respectively), without compromising karyotype integrity, telomere length, or safety in vivo.

Conclusion: XT-Thrive provides superior pre-freeze stability, post-thaw recovery, expansion potential, and osteogenic functionality compared to CS10, while maintaining MSC identity and genomic stability. These results support XT-Thrive as a promising DMSO-free alternative for clinical-grade MSC biobanking and manufacturing.

Bone defect repair faces clinical challenges due to complex conditions caused by various factors such as trauma and aging. Traditional treatments have certain limitations, which seriously affect patients' prognosis. As the core organelle of cells, mitochondria regulate the activity of key cells including osteoblasts, osteoclasts, and bone marrow mesenchymal stem cells through functions such as oxidative phosphorylation (OXPHOS), production and scavenging of reactive oxygen species (ROS), regulation of Ca²⁺ concentration, modulation of cell death, and immune response, as well as dynamic processes including fusion, fission, mitophagy, and transport. Moreover, mitochondria interact synergistically with the neuro-vascular-muscle axis, participating deeply in bone defect repair. This article systematically reviews the mechanisms and research progress of mitochondria in bone defect repair, providing a theoretical basis for the development of novel mitochondria-targeted repair strategies and facilitating the research and development of efficient clinical treatment regimens. This will help to develop new treatment strategies for bone defects. These strategies will be more effective, safe and targeted for individual patients.