APL Bioengineering最新文献

{"title":"Activation of cGAS-STING axis by CO@OMVs promote macrophage mitophagy for CIRI treatment.","authors":"Yiwei Chen, Shuntong Hu, Juan Huang, Pangyao Long, Jiahao Zhou, Longfeng Ran, Jinze Wu, Xiaobo Li, Huaizheng Liu, Yi Yuan, Dujie Xie","doi":"10.1063/5.0345675","DOIUrl":"10.1063/5.0345675","url":null,"abstract":"<p><p>This study investigates the effects of nanobody-engineered bacterial outer membrane vesicles (CO@OMVs) on cGAS-STING-associated signaling, macrophage mitophagy, and cerebral ischemia-reperfusion injury (CIRI). Following extraction and characterization of CO@OMVs, <i>in vitro</i> experiments in RAW 264.7 macrophages demonstrated increased levels of cGAS-STING-associated signaling molecules, enhanced mitophagy, increased tumor necrosis factor-α (TNF-α) secretion, and decreased IL-6 secretion. In a CIRI mouse model, CO@OMVs reduced local inflammatory markers and apoptosis and improved cognitive and neurobehavioral functions. Multi-omics analyses further supported the therapeutic potential of CO@OMVs in mitigating early brain injury.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"10 3","pages":"036110"},"PeriodicalIF":4.9,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13619348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149076323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomechanical stress unmasks a fibroblast-dependent hypercontractile-disarray phenotype in MYBPC3 truncation HCM.","authors":"Huanzhu Jiang, Ganesh Malayath, Nongmaithem Debeni Devi, Hsin-Yi Cindy Chou, Yasaman Kargar Gaz Kooh, Jingxuan Guo, Ghiska Ramahdita, Jenna Nguyen, Riya Bhakta, Lavanya Aryan, Sharon Cresci, Nathaniel Huebsch","doi":"10.1063/5.0336866","DOIUrl":"10.1063/5.0336866","url":null,"abstract":"<p><p>Hypertrophic cardiomyopathy (HCM) is commonly caused by pathogenic variants in the sarcomere, such as truncations in myosin-binding protein C (MYBPC3), yet clinical severity and adverse outcomes correlate poorly with genotype alone and are strongly influenced by fibrosis. We developed an engineered human micro-heart tissue (<i>μ</i>HT) combining iPSC-derived cardiomyocytes (CM) with defined primary cardiac fibroblast (cFB) fractions and mechanically modulated afterload. This design allowed us to test how stromal context and pro-fibrotic signaling shape HCM pathogenesis in micro-engineered heart tissues made from iPSCs harboring an HCM-linked frameshift variant in <i>MYBPC3</i> (MYBPC3fs). Under low afterload, genotype-associated differences in total active force were limited at 0% and 5% added cFB but became apparent at 25% added cFB. However, high afterload markedly amplified MYBPC3fs <i>μ</i>HT hypercontractility, with tissues generating greater total active force at both 5% and 25% added cFB. We also observed afterload- and cFB-dependent remodeling of Ca²⁺ handling, indicating that excitation-contraction coupling in MYBPC3fs tissues is modulated by combinatorial actions of mechanical stress and the stromal environment. Despite heightened contractile output, the MYBPC3fs <i>μ</i>HT exhibited blunted improvements in Z-disc alignment with increasing cFB content, whereas cardiomyocytes within the isogenic control <i>μ</i>HT showed progressive structural ordering as cFB density increased. Finally, the MYBPC3fs <i>μ</i>HT exhibited a greater response to TGF-β, leading to exaggerated increases in tissue-level resting tension and α-smooth muscle actin expression. Our findings provide important insights into the pathophysiologic pathways leading to adverse outcomes in clinical HCM and a foundation for future studies of cardiomyocyte-fibroblast interactions in HCM.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"10 3","pages":"036109"},"PeriodicalIF":4.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13574545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148971677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shape factor analysis as a quantitative framework for assessing spheroid and organoid morphology and invasiveness.","authors":"Brittany E Schutrum, Jenny Deng, Ju Hee Kim, Amalie Gao, Emily Hur, Jack C Crowley, Lu Ling, Matalin G Pirtz, Coulter Q Ralston, Alexander Yu Nikitin, Claudia Fischbach","doi":"10.1063/5.0333152","DOIUrl":"10.1063/5.0333152","url":null,"abstract":"<p><p>Morphological changes in spheroids and organoids are widely used as <i>in vitro</i> indicators of healthy and diseased tissue function, but selecting appropriate methods to quantify these changes remains challenging. Shape factors (or shape descriptors) are dimensionless metrics often computed using ImageJ/FIJI; however, their ability to classify specific morphological features can vary. To address this challenge, we developed a clinically inspired, custom MATLAB algorithm to quantify the variance in radial lengths of invasive protrusions in spheroids and organoids. We then compared the advantages and limitations of this approach with conventional ImageJ/FIJI shape descriptors to guide users in selecting the most appropriate method for classifying spheroid and organoid morphology in their specific settings. To this end, we first analyzed digital phantoms and then performed the same comparisons using images from experimental spheroid and organoid datasets. By enabling numerical morphological readouts, shape factor analysis can enhance phenotypic profiling of spheroids and organoids and provide valuable metrics for <i>in vitro</i> studies, including high-throughput and drug screening workflows.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"10 3","pages":"036101"},"PeriodicalIF":4.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13322776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148370317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HB-EGF enhances collective cell migration via spatial coordination of traction.","authors":"Jonah J Spencer, Emily Rhine, Pamela K Kreeger, Jacob Notbohm","doi":"10.1063/5.0326208","DOIUrl":"10.1063/5.0326208","url":null,"abstract":"<p><p>An important process in wound healing is re-epithelialization, wherein cells collectively migrate to cover the wounded area. Here, we investigate how cellular forces lead to the migration of an epithelial monolayer in a wound healing assay. We report that heparin-bound epidermal growth factor (HB-EGF) increased the rate of collective migration in a phospholipase C-dependent manner through a combination of increased cell speed and straighter, more coordinated motion. Using traction force microscopy, we found that HB-EGF increased the forces within the cell monolayer, producing a competition between elevated traction at the edge of the monolayer and elevated stress within the bulk of the monolayer. To investigate how this interplay led to faster monolayer migration, we used a theoretical model for collective cell migration, which, when compared against the experimental data, suggested faster migration resulted from increased active propulsive forces at both the leading edge and within the bulk of the cell monolayer. Experimental analysis of actin stress fibers and vinculin foci supported inferences made from the model. Combined, our results support that HB-EGF induced a greater magnitude of traction for cells at the edge of the monolayer and aligned the direction of traction for cells within the bulk, thereby leading to faster and more persistent collective migration.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"10 2","pages":"026108"},"PeriodicalIF":4.9,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13290391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148319728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A pump-free microfluidic device for integrated multi-functional testing of tumor spheroids.","authors":"Eliana Steinberg, Gabriel D Azulay, Alina Ruiz de Villa, Ouri Schwob, Ofra Benny","doi":"10.1063/5.0329306","DOIUrl":"10.1063/5.0329306","url":null,"abstract":"<p><p>Three-dimensional (3D) multicellular <i>ex vivo</i> cultures have become central tools for cancer research and drug testing under physiologically relevant conditions. Organ-on-a-chip technologies based on microfluidics provide platforms for culturing and analyzing 3D tissues under flow. However, maintaining long-term continuous perfusion typically requires pumps and complex tubing networks, increasing operational complexity, cost, and limiting scalability for routine use. Pumpless approaches have been explored but often suffer from short flow duration, inconsistent unidirectional perfusion, and frequent reservoir replenishment. Here, we present a vertical pump-free fluidic platform designed for spheroid formation, culture, and biological testing. The system integrates molds for spheroid assembly with a modular 3D-printed culture chamber that allows direct sample access. A stackable cartridge-like design enables parallel assays under identical conditions, while the incorporation of commercially available syringes as structural elements improves standardization and reduces the footprint. Continuous perfusion over several days is achieved using a hydrogel-based flow resistor that generates passive pressure gradients. Using three human ovarian cancer cell lines (Ovcar-3, A2780, and Ovcar-8), we demonstrate the formation of uniform spheroids that maintain viability and metabolic activity for up to one week within the 3D-printed cartridges. Drug response was evaluated using paclitaxel, with measurable effects on spheroid growth and invasion. Flow simulations and experimental measurements confirm stable perfusion for approximately 3 days, followed by a gradual decline until cessation at day 7. Overall, this pump-free platform provides a scalable, modular solution for controlled 3D culture and multi-functional assays without external pumping systems.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"10 2","pages":"026107"},"PeriodicalIF":4.9,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13286704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148309777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Photobiomodulation outperforms ultrasound in reducing IL-1 <b><i>β</i></b> -driven chondrocyte inflammation.","authors":"Sofia Oliveira, Débora Ferreira, Ligia R Rodrigues, Filipe S Silva, Betina B Hinckel, Óscar Carvalho, Ana Leal","doi":"10.1063/5.0323327","DOIUrl":"10.1063/5.0323327","url":null,"abstract":"<p><p>Therapeutic ultrasound (US) and photobiomodulation (PBM) are promising treatment modalities for restoring articular cartilage. Owing to their different mechanisms of action, individual or combined stimulation may elicit different bioeffects on chondrocytes. This study aimed to evaluate the potential of US and PBM, applied alone or combined, in augmenting chondrocytes' responses toward cartilage matrix synthesis and reverting their catabolic activities, with or without interleukin-1β (IL-1β) incubation. Human chondrocytes were cultured under basal or proinflammatory conditions (1 ng/ml IL-1β) and stimulated daily for 6 days with US, PBM, US followed by PBM, and PBM followed by US. Chondrocyte activity, along with protein and mRNA expression of cartilage synthesis- and degradation-related markers, was analyzed. IL-1β incubation did not significantly affect chondrocytes' metabolic activity or sulfated glycosaminoglycans (GAGs) production. Both US and PBM, alone or combined, increased the protein and mRNA of collagen type II (<i>COL II</i>) and aggrecan (<i>ACAN</i>) under basal and proinflammatory conditions. PBM had a stimulatory effect on GAG synthesis. While PBM did not influence the expression of cartilage destruction markers, US potentiated the chondrocytes' response to inflammation by increasing metalloproteinases and <i>IL-1β</i> mRNA levels. The sequential combination of US and PBM induced distinct bioeffects depending on the application order, but these were not superior to the effects of individual treatments. As this study used chondrocytes from a single donor, generalizability may be limited. While both US and PBM stimulated matrix synthesis, PBM showed a comparatively greater ability to mitigate chondrocyte degradation and may be of interest for cartilage repair strategies.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"10 2","pages":"026106"},"PeriodicalIF":4.9,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13249530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148220141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research progress of 3D-printed anti-infective bone tissue engineering scaffolds based on triply periodic minimal surface structures.","authors":"Peijie Zhao, Yafeng Zhang, Zewen Qiao","doi":"10.1063/5.0334789","DOIUrl":"10.1063/5.0334789","url":null,"abstract":"<p><p>Bone defect repair remains a significant clinical challenge, necessitating scaffold materials that combine excellent mechanical properties, bioactivity, and anti-infective capabilities, which are central to bone tissue engineering. Triply periodic minimal surface (TPMS) structures have garnered considerable attention due to their superior mechanical and biological characteristics, demonstrating great potential in the design of bone repair scaffolds. This review summarizes the latest advances in three-dimensional printed anti-infective tissue engineering scaffolds based on TPMS structures within the field of bone regeneration. It highlights the design advantages of TPMS architectures, the performance of composite materials such as polylactic acid/magnesium titanate, and the antimicrobial mechanisms of these scaffolds. Furthermore, the synergistic effects of promoting osteogenesis and combating infection are analyzed. By systematically collating current research findings, this article aims to provide a theoretical foundation and guidance for the development of next-generation multifunctional bone repair materials.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"10 2","pages":"021506"},"PeriodicalIF":4.9,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13241247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148200680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platelet membrane-coated nanoparticles: Bioengineering principles, quality control, and translational opportunities.","authors":"Ncobile Bagezile Mdlovu, Liling Delila, Si-Han Wu, Thierry Burnouf","doi":"10.1063/5.0315665","DOIUrl":"10.1063/5.0315665","url":null,"abstract":"<p><p>Platelet membranes (PMs) are increasingly explored as bioinspired coatings for nanoparticles (NPs), providing improved immune evasion, prolonged circulation, and disease-homing properties that enhance targeted drug delivery. Unlike conventional NPs that rely mainly on passive targeting, PM-coated systems expose platelet surface markers such as CD47, GPIb, and P-selectin, enabling vascular adhesion and selective localization to tumors or thrombi. PM-NPs are thus increasingly regarded as promising carriers for oncology, cardiovascular, and infectious disease therapies. This review introduces the various bioengineering principles underlying PM-NP fabrication, including points to consider for platelet sourcing, membrane isolation, and coating strategies. Achieving reliable quality control (QC) and reproducibility depends on rigorous assessment of critical formulation variables, including nanoparticle size, surface charge, and the preservation of functional membrane proteins. The implementation of scientific approaches and regulatory standardization frameworks, such as the Minimal Information for Studies of Extracellular Vesicles guidelines, and Food and Drug Administration/European Medicines Agency (FDA/EMA) regulatory expectations, is critical to establish reproducibility and facilitate regulatory acceptance of PM-NP technologies, guiding their advancement toward clinical-grade production. Furthermore, we highlight translational opportunities and the complementary potential of platelet-derived extracellular vesicles, which share similar surface markers, yet offer intrinsic nanoscale size, endogenous bioactivity, and improved stability. By integrating robust engineering design with standardized QC practices, PM-NPs can progress from laboratory research to clinically viable therapeutics, establishing a relevant benchmark for future cell membrane-based nanomedicines.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"10 2","pages":"021505"},"PeriodicalIF":4.9,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13197205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148018170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomolecular and cellular chirality: Novel diagnostic perspectives for diseases.","authors":"Xinwei Guo, Yi Zheng, Weifang Zhang, Hua Yao","doi":"10.1063/5.0323602","DOIUrl":"10.1063/5.0323602","url":null,"abstract":"<p><p>Chirality is an intrinsic characteristic of living systems, manifesting as a pervasive asymmetry from the molecular to the cellular level. This asymmetry regulates normal life activities through precise stereospecific recognition between molecules and between molecules and cells. Under physiological conditions, L-amino acids constitute proteins that support metabolic functions, right-handed helical deoxyribonucleic acid (DNA) stores genetic information, and right-handed sugars provide energy. At the cellular level, the non-centrosymmetric arrangement of the cytoskeleton guides the left-right axial positioning during embryonic development and organ formation. A certain degree of chiral inversion occurs under normal physiological conditions-for instance, trace amounts of D-amino acids modulate neurotransmitter release, and low level of left-handed DNA promotes double-strand unwinding, facilitating transcription. However, excessive accumulation of D-amino acids is closely associated with Alzheimer's disease, chronic kidney di'ease, diabetes, and aging. Similarly, the presence of substantial left-handed DNA fragments can lead to genomic instability, \"increasin\" sus'eptibility to tumorigenesis. Moreover, abnormalities in cellular chirality may contribute to vascular endothelial barrier disruption and improper left-right organ positioning. Therefore, monitoring aberrant chiral molecules and cells that deviate from the normal range holds promise for the early diagnosis of diseases such as nephropathy, Alzheimer's disease, diabetes, and cancer. This article primarily reviews the dynamic chiral balance under physiological and pathological conditions, providing a reference for the application of chirally inverted molecules and cells Is potential novel biomarkers for the early diagnosis of diseases.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"10 2","pages":"021504"},"PeriodicalIF":4.9,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13193766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148018147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Flow molecular dynamics simulations reveal mechano-presentation of von Willebrand factor through glycan-modulated autoinhibitory modules.","authors":"Naveen Eugene Louis Richard Louis, Yunduo Charles Zhao, Lining Arnold Ju","doi":"10.1063/5.0329754","DOIUrl":"10.1063/5.0329754","url":null,"abstract":"<p><p>Force-induced protein conformational changes govern many essential biological processes, yet their molecular mechanisms remain difficult to resolve. Von Willebrand factor (VWF), a central regulator of hemostasis, is activated by hydrodynamic forces in blood flow, but how mechanical signals propagate across its multidomain architecture is poorly understood. Here, we use flow molecular dynamics (FMD), a simulation framework that applies fluid forces via controlled solvent flow to interrogate mechanosensitive proteins. Using VWF as a model system, we reconstructed the complete mechanomodule (D'D3-A1-A2-A3; 1110 residues) with native glycosylation by integrating crystallographic data and ColabFold predictions. FMD simulations capture a force-driven transition from a compact, autoinhibited \"bird's nest\" ensemble to an extended, activated state, revealing asymmetric autoinhibitory strengths within the N'AIM and C'AIM modules of the A1 domain. By directly linking static structures to dynamic, force-regulated behavior, this work establishes a generalizable platform for dissecting protein mechanosensitivity and enabling the rational design of force-responsive therapeutics.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"10 2","pages":"026105"},"PeriodicalIF":4.9,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13171254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147942825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}