APL Bioengineering最新文献_第2页

A modular and reconfigurable microfluidic device for culturing spheroids under continuous perfusion. 一种用于连续灌注培养球体的模块化可重构微流控装置。

IF 4.1 3区医学

APL Bioengineering Pub Date : 2025-08-13 eCollection Date: 2025-09-01 DOI: 10.1063/5.0262536

Hiba Aljayyousi, Sarah Sahloul, Ajymurat Orozaliev, Navajit Baban, Anh-Duc Van, Amani Al Nuairi, Pauline John, Azhar Zam, Piergiorgio Percipalle, Yong-Ak Song

{"title":"A modular and reconfigurable microfluidic device for culturing spheroids under continuous perfusion.","authors":"Hiba Aljayyousi, Sarah Sahloul, Ajymurat Orozaliev, Navajit Baban, Anh-Duc Van, Amani Al Nuairi, Pauline John, Azhar Zam, Piergiorgio Percipalle, Yong-Ak Song","doi":"10.1063/5.0262536","DOIUrl":"10.1063/5.0262536","url":null,"abstract":"3D cell spheroids have become crucial in vitro models for biomedical research, yet maintaining their growth and viability remains challenging due to diffusion limitations. We developed a versatile microfluidic modular device with a reconfigurable channel design that is customizable by altering the channel configuration in the adhesive layer. The resealable adhesive layer also enables open access to the wells for loading cells, continuous perfusion after closing, and facile retrieval of spheroids for downstream analysis and imaging after culturing. We evaluated three channel configurations using Mouse Embryonic Fibroblasts (MEFs), human induced Pluripotent Stem Cells (hiPSCs), and MDA-MB-231 breast cancer cells. The device significantly improved spheroid growth in MEFs and hiPSCs, increasing up to 139.9% over controls in 14 days. In contrast, MDA-MB-231 spheroids exhibited slower growth, highlighting the need for balancing nutrient delivery with autocrine factor retention. Sphericity was maintained in MEF and MDA-MB-231 spheroids, while hiPSC spheroids experienced budding. In situ optical coherence tomography (OCT) provided noninvasive 3D viability assessments of the spheroids. Our findings demonstrate that this modular microfluidic device, combined with OCT analysis, offers a powerful platform for advancing spheroid culture techniques and opens up new opportunities in applications such as drug testing, studying spheroid-spheroid interactions, and collecting spheroid secretions.","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"9 3","pages":"036111"},"PeriodicalIF":4.1,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12352930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144875871","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}

引用次数: 0

Mechanobiological engineering strategies for organoid culture. 类器官培养的机械生物学工程策略。

IF 4.1 3区医学

APL Bioengineering Pub Date : 2025-07-18 eCollection Date: 2025-09-01 DOI: 10.1063/5.0275439

Mohsen Taghizadeh, Ali Taghizadeh, Hye Sung Kim

引用次数: 0

TTLL4 mediates the PI3K/AKT/MDM2 pathway to promote hepatocellular carcinoma progression and predict patient prognosis. TTLL4介导PI3K/AKT/MDM2通路，促进肝细胞癌进展，预测患者预后。

IF 6.6 3区医学

APL Bioengineering Pub Date : 2025-06-30 eCollection Date: 2025-06-01 DOI: 10.1063/5.0267938

Zeping He, Desheng Chen, Lei Li, Shanbao Li, Fangbin Song, Jinfeng Cai, Xueyan Guo, Yaohao Luo, Xinshuai Wang, Zeping Chen, Junming Xu

{"title":"TTLL4 mediates the PI3K/AKT/MDM2 pathway to promote hepatocellular carcinoma progression and predict patient prognosis.","authors":"Zeping He, Desheng Chen, Lei Li, Shanbao Li, Fangbin Song, Jinfeng Cai, Xueyan Guo, Yaohao Luo, Xinshuai Wang, Zeping Chen, Junming Xu","doi":"10.1063/5.0267938","DOIUrl":"10.1063/5.0267938","url":null,"abstract":"Hepatocellular carcinoma (HCC) is a highly lethal and heterogeneous tumor driven by the dysregulation of multiple genes. Tubulin tyrosine ligase-like 4 (TTLL4) has been linked to tumor progression, but its specific role in HCC pathogenesis remains unclear. RNA sequencing data, somatic mutation profiles, and clinical characteristics were analyzed from TCGA, GEO, and TIMER databases. The effects of TTLL4 on cell proliferation, migration, and apoptosis were studied using functional assays and flow cytometry. In vivo, tumor growth and metastasis were evaluated through subcutaneous implantation and tail vein injection. Immunohistochemistry assessed TTLL4 and Ki-67 expression. TTLL4 was upregulated in HCC and associated with poor prognosis, linking it to cancer progression and the PI3K-AKT signaling pathway. Knockdown of TTLL4 in HCC cells reduced proliferation, migration, and colony formation while increasing apoptosis. In vivo, TTLL4 knockdown slowed tumor growth and reduced lung metastasis. It also decreased the expression of proteins in the PI3K/AKT/MDM2 pathway, while overexpression upregulated these proteins. Rescue experiments further suggest that TTLL4 may exert its regulatory effects on this pathway by modulating PI3K expression levels. TTLL4 plays a significant role in HCC progression via the PI3K/AKT/MDM2 pathway and may serve as a novel therapeutic target for HCC diagnosis and treatment.","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"9 2","pages":"026128"},"PeriodicalIF":6.6,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12212963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144545375","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}

引用次数: 0

Mechanical cues orchestrate monocyte behavior in immune regulation and disease. 机械信号在免疫调节和疾病中协调单核细胞的行为。

IF 4.1 3区医学

APL Bioengineering Pub Date : 2025-06-27 eCollection Date: 2025-06-01 DOI: 10.1063/5.0268234

Yifan Lin, Hardik Makkar, Shuchen Zhang, Bingling Chen, Chaoning Zhan, Kyle Vining

{"title":"Mechanical cues orchestrate monocyte behavior in immune regulation and disease.","authors":"Yifan Lin, Hardik Makkar, Shuchen Zhang, Bingling Chen, Chaoning Zhan, Kyle Vining","doi":"10.1063/5.0268234","DOIUrl":"10.1063/5.0268234","url":null,"abstract":"Monocytes, key mediators of innate immunity, exhibit remarkable sensitivity to mechanical cues such as extracellular matrix (ECM) stiffness, substrate rigidity, shear stress, compression, and hydrostatic pressure, which shape their activation, differentiation, and functional polarization. Monocytes develop from the bone marrow and populate the vasculature throughout the body. During inflammation, they are recruited to injured or diseased tissues by chemokines and proinflammatory cytokines, modulating local immune responses during embryonic development and adulthood via mechanosensing and mechanotransduction pathways. This review synthesizes recent advances in monocyte mechanobiology. It highlights how the bone marrow ECM mechanics orchestrates myelopoiesis, the role of endothelium and hemodynamic forces in migration, and how tissue mechanics influences monocyte fate in chronic inflammation, fibrosis, and cancer. We discuss the mechanosensitive pathways that govern monocyte behavior in health and disease and therapeutic opportunities that emerge from targeting these mechanisms via biomaterial approaches. Additionally, future directions toward developing mechanotherapy for immune modulation are discussed. By bridging mechanobiology and immunology, this review underscores the potential of mechanical cues as therapeutic targets to reprogram monocyte behavior in disease.","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"9 2","pages":"021506"},"PeriodicalIF":4.1,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12205964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530319","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}

引用次数: 0

Recent advancements in polymer science for retinal diseases: New frontiers in drug delivery systems. 视网膜疾病聚合物科学的最新进展：药物输送系统的新领域。

IF 6.6 3区医学

APL Bioengineering Pub Date : 2025-06-27 eCollection Date: 2025-06-01 DOI: 10.1063/5.0264382

Weiliang Wang, Nancy Wang, Xinxin Zhao, Xinyi Su, Zengping Liu

{"title":"Recent advancements in polymer science for retinal diseases: New frontiers in drug delivery systems.","authors":"Weiliang Wang, Nancy Wang, Xinxin Zhao, Xinyi Su, Zengping Liu","doi":"10.1063/5.0264382","DOIUrl":"10.1063/5.0264382","url":null,"abstract":"Retinal diseases, such as age-related macular degeneration and diabetic macular edema, are significant contributors to vision loss. While injection of anti-vascular endothelial growth factors is the current gold standard treatment, their invasive nature reduces patient compliance and treatment outcomes and increases the risk of complications. In this review, we explore the recent advancements in drug delivery systems designed to overcome ocular barriers to effectively deliver drugs to the retina. We examine advancements in intravitreal injections, such as novel formulations, therapeutic molecules, and sustained-release implants. Moreover, we discuss innovations in noninvasive strategies, such as topical delivery systems incorporating cell-penetrating peptides, solid lipid nanoparticles, dendrimers, and nano-micelles. These technologies aim to enhance drug penetration, stability, and bioavailability. Although preclinical and clinical trials have yielded promising results, challenges remain in ensuring long-term safety and efficacy. This review highlights future research directions to optimize these approaches and develop more effective, patient-friendly therapies for retinal diseases.","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"9 2","pages":"020902"},"PeriodicalIF":6.6,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12205963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530320","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}

引用次数: 0

Epigenetic regulation and mechanobiological adaptation in tenocytes during maturation. 细胞成熟过程中的表观遗传调控和机械生物学适应。

IF 6.6 3区医学

APL Bioengineering Pub Date : 2025-06-26 eCollection Date: 2025-06-01 DOI: 10.1063/5.0271050

Ellen Y Zhang, Tyler E Blanch, Saeed B Ahmed, Xi Jiang, Nathaniel A Dyment, Su Chin Heo

{"title":"Epigenetic regulation and mechanobiological adaptation in tenocytes during maturation.","authors":"Ellen Y Zhang, Tyler E Blanch, Saeed B Ahmed, Xi Jiang, Nathaniel A Dyment, Su Chin Heo","doi":"10.1063/5.0271050","DOIUrl":"10.1063/5.0271050","url":null,"abstract":"Tendons are essential for musculoskeletal function, facilitating movement by transmitting forces from muscles to bones. However, aging alters the tendon microenvironment, disrupting the delicate interactions between tenocytes and the extracellular matrix (ECM), contributing to tissue degeneration. While prior studies have characterized the mechanical and structural changes in tendons during maturation, the epigenetic regulation of tenocyte function during aging remains poorly understood. Here, we investigate age-dependent mechanobiological and epigenetic changes in murine tenocytes. Our findings demonstrate that mature tenocytes generate higher traction forces and migrate faster. Furthermore, we reveal increased chromatin condensation in mature tenocytes, accompanied by elevated levels of the repressive histone mark H3K27me3 and reduced levels of the activating mark H3K4me3. Chromatin immunoprecipitation sequencing indicates that these histone modifications regulate genes associated with cellular contractility, ECM production, and mechanotransduction, highlighting the critical role of epigenetic mechanisms in governing tenocyte function. These findings suggest that age-related epigenetic changes may contribute to both the maintenance of tissue homeostasis and the suppression of degenerative diseases in tendons, providing new avenues for therapeutic strategies aimed at restoring tenocyte function and enhancing tendon regeneration.","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"9 2","pages":"026127"},"PeriodicalIF":6.6,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530318","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}

引用次数: 0

Applying physical principles to cancer research. 将物理原理应用于癌症研究。

IF 6.6 3区医学

APL Bioengineering Pub Date : 2025-06-26 eCollection Date: 2025-06-01 DOI: 10.1063/5.0282296

Claudia Fischbach, Corey S O'Hern, Adam J Engler

引用次数: 0

The mechanobiology of fibroblast activation in disease. 成纤维细胞在疾病中活化的机械生物学。

IF 6.6 3区医学

APL Bioengineering Pub Date : 2025-06-18 eCollection Date: 2025-06-01 DOI: 10.1063/5.0272393

Yeji Chang, Jia Wen Nicole Lee, Andrew W Holle

{"title":"The mechanobiology of fibroblast activation in disease.","authors":"Yeji Chang, Jia Wen Nicole Lee, Andrew W Holle","doi":"10.1063/5.0272393","DOIUrl":"10.1063/5.0272393","url":null,"abstract":"Fibroblasts play crucial roles in wound healing, cancer, and fibrosis. Many aspects of these roles are driven by the process known as fibroblast activation. The generally accepted definition of fibroblast activation is the transition from a quiescent state to a state in which fibroblasts participate in a number of active processes, including extracellular matrix (ECM) production and remodeling, elevated contractility, and enhanced migratory capacity, although there is no universal consensus on what exactly constitutes \"activation.\" Interestingly, the time scale of activation is not consistent across tissues and disease states; some fibroblasts quickly return to quiescence after activation (e.g., in wound healing), others undergo apoptosis, while a subset become persistently activated. This activation, both acute and persistent, is inherently a mechanical process, given the increase in ECM production and remodeling and the enhanced traction force generation. Thus, there exists a dynamic reciprocity, or cell-ECM feedback, in which activated fibroblasts produce a mechanical microenvironment that in turn supports persistent activation. This has a wide variety of implications for disease, most notably fibrosis and cancer, as the fibroblasts that become persistently activated in connection with these conditions can contribute to disease state progression. Like other mechanosensitive processes, this mechanically induced persistent fibroblast activation is driven by a number of mechanotransduction signaling pathways. Thus, an opportunity exists in which the mechanosensitive underpinning of fibroblast activation can be leveraged to improve clinical outcomes. Here, we highlight these opportunities and make a call to the field to consider the mechanosensitive pathways governing fibroblast activation as an important frontier in mechanomedicine.","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"9 2","pages":"021505"},"PeriodicalIF":6.6,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12178607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144334123","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}

引用次数: 0

Astrocyte-driven vasoconstriction impairs glymphatic clearance in a human tauopathy-on-chip model. 星形胶质细胞驱动的血管收缩损害了人类芯片上的牛头病变模型中的淋巴清除。

IF 6.6 3区医学

APL Bioengineering Pub Date : 2025-06-16 eCollection Date: 2025-06-01 DOI: 10.1063/5.0261875

Rena Park, Yansong Peng, Aria R Yslas, Esak Lee

{"title":"Astrocyte-driven vasoconstriction impairs glymphatic clearance in a human tauopathy-on-chip model.","authors":"Rena Park, Yansong Peng, Aria R Yslas, Esak Lee","doi":"10.1063/5.0261875","DOIUrl":"10.1063/5.0261875","url":null,"abstract":"The glymphatic system is a critical pathway for clearing metabolic waste from the brain by mediating cerebrospinal fluid and interstitial fluid exchange. In Alzheimer's disease (AD), tau protein accumulation is strongly associated with impaired glymphatic clearance, yet the underlying mechanism remains poorly defined. In this study, we employed a three-dimensional human glymphatics-on-chip model to investigate fluid transport and mass clearance in a brain-mimetic extracellular matrix containing engineered blood vessels (BV) surrounded by primary astrocytes. We found that phosphorylated tau (p-tau) induced morphological transformation of astrocytes into a hypertrophic, hypercontractile state, leading to astrocyte-mediated vasoconstriction and impaired glymphatic clearance. Notably, p-tau did not affect blood endothelial cells directly, implicating astrocyte-dependent mechanisms in glymphatic deregulation. Pharmacological inhibition of non-muscle myosin II with blebbistatin reversed astrocytic hypercontractility, restored BV diameters, and rescued glymphatic function. These findings elucidate a glial-specific mechanism of tau-induced glymphatic dysfunction and underscore astrocytic contractility as a promising therapeutic target in AD.","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"9 2","pages":"026126"},"PeriodicalIF":6.6,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12173474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318359","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}

引用次数: 0

Decoding force-transmission linkages for therapeutic targeting and engineering. 解码力-传输联系的治疗靶向和工程。

IF 6.6 3区医学

APL Bioengineering Pub Date : 2025-06-13 eCollection Date: 2025-06-01 DOI: 10.1063/5.0267032

Jingzhun Liu, Yunxin Deng, Jie Yan

{"title":"Decoding force-transmission linkages for therapeutic targeting and engineering.","authors":"Jingzhun Liu, Yunxin Deng, Jie Yan","doi":"10.1063/5.0267032","DOIUrl":"10.1063/5.0267032","url":null,"abstract":"Mechanosensing and mechanotransduction enable cells to perceive and respond to mechanical forces, underpinning essential physiological processes and disease pathways. Central to these phenomena are force-transmission supramolecular linkages, which undergo structural transitions and regulate signaling proteins in response to mechanical stimuli. This review examines the mechanisms of these force-bearing linkages, focusing on force duration, dictated by the stability of protein-protein interfaces, and force-dependent mechanical structural changes of force-bearing domains in the linkage, which activates or deactivates mechanosensing domains. We discuss the emerging potential of these linkages as pharmaceutical targets, exploring drugs and peptides designed to modulate these mechanical properties. In addition, we highlight the application of artificial intelligence in protein engineering to enhance therapeutic precision by dynamically tuning these mechanosensing characteristics. Our synthesis of current findings and future perspectives aims to inform novel approaches to drug design and inspire future research in the field of mechanomedicine.","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"9 2","pages":"021504"},"PeriodicalIF":6.6,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12166987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303265","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}

引用次数: 0