APL Bioengineering最新文献

{"title":"Hydrodynamic efficient cell capture and pairing method on microfluidic cell electrofusion chip.","authors":"Xuefeng Wang, Yaqi Bai, Xiaoling Zhang, Wei Li, Jun Yang, Ning Hu","doi":"10.1063/5.0250472","DOIUrl":"10.1063/5.0250472","url":null,"abstract":"<p><p>Cell fusion is a widely employed process in various biological procedures, demonstrating significant application value in biotechnology. Cell pairing is a crucial manipulation for cell fusion. Standard fusion techniques, however, often provide poor and random cell contact, leading to low yields. In this study, we present a novel microfluidic device that utilizes a three-path symmetrical channel hydrodynamic capture method to achieve high-efficiency cell capture and pairing. The device contains several symmetrical channels and capture units, enabling three-path capture of two kinds of cells. To better understand the conditions necessary for effective cell pairing, we established a theoretical model of the three-path trapping flow field and conducted a qualitative force analysis on cells. Using K562 cells to explore the effect of different volumetric flow ratios of symmetric channels on cell capture and pairing efficiency, we finally got the optimized structure and obtained a single-cell capture efficiency of approximately 95.6 ± 2.0% and a cell pairing efficiency of approximately 83.3 ± 8.8%. Subsequently, electrofusion experiments were carried out on the paired cells, resulting in a fusion efficiency of approximately 77.8 ± 9.6%.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"9 1","pages":"016111"},"PeriodicalIF":6.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574329","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":"Adenine base editing rescues pathogenic phenotypes in tissue engineered vascular model of Hutchinson-Gilford progeria syndrome.","authors":"Nadia O Abutaleb, Xin D Gao, Akhil Bedapudi, Leandro Choi, Kevin L Shores, Crystal Kennedy, Jordyn E Duby, Kan Cao, David R Liu, George A Truskey","doi":"10.1063/5.0244026","DOIUrl":"10.1063/5.0244026","url":null,"abstract":"<p><p>The rare, accelerated aging disease Hutchinson-Gilford Progeria Syndrome (HGPS) is commonly caused by a <i>de novo</i> c.1824 C > T point mutation of the <i>LMNA</i> gene that results in the protein progerin. The primary cause of death is a heart attack or stroke arising from atherosclerosis. A characteristic feature of HGPS arteries is loss of smooth muscle cells. An adenine base editor (ABE7.10max) corrected the point mutation and produced significant improvement in HGPS mouse lifespan, vascular smooth muscle cell density, and adventitial fibrosis. To assess whether base editing correction of human HGPS tissue engineered blood vessels (TEBVs) prevents the HGPS vascular phenotype and to identify the minimum fraction of edited smooth muscle cells needed to effect such changes, we transduced HGPS iPSCs with lentivirus containing ABE7.10max. Endothelial cells (viECs) and smooth muscle cells (viSMCs) obtained by differentiation of edited HGPS iPSCs did not express progerin and had double-stranded DNA breaks and reactive oxygen species at the same levels as healthy viSMCs and viECs. Editing HGPSviECs restored a normal response to shear stress. Normal vasodilation and viSMC density were restored in TEBVs made with edited cells. When TEBVs were prepared with at least 50% edited smooth muscle cells, viSMC proliferation and myosin heavy chain levels significantly improved. Sequencing of TEBV cells after perfusion indicated an enrichment of edited cells after 5 weeks of perfusion when they comprised 50% of the initial number of cells in the TEBVs. Thus, base editing correction of a fraction of HGPS vascular cells improves human TEBV phenotype.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"9 1","pages":"016110"},"PeriodicalIF":6.6,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11871533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543717","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":"Electrospinning strategies targeting fibroblast for wound healing of diabetic foot ulcers.","authors":"Long Chen, Ping Wu, Yu Zhu, Han Luo, Qiang Tan, Yongsong Chen, Dan Luo, Zhiyong Chen","doi":"10.1063/5.0235412","DOIUrl":"https://doi.org/10.1063/5.0235412","url":null,"abstract":"<p><p>The high incidence and prevalence of diabetic foot ulcers (DFUs) present a substantial clinical and economic burden, necessitating innovative therapeutic approaches. Fibroblasts, characterized by their intrinsic cellular plasticity and multifunctional capabilities, play key roles in the pathophysiological processes underlying DFUs. Hyperglycemic conditions lead to a cascade of biochemical alterations that culminate in the dysregulation of fibroblast phenotype and function, which is the primary cause of impaired wound healing in DFUs. Biomaterials, particularly those engineered at the nanoscale, hold significant promise for enhancing DFU treatment outcomes. Electrospun nanofiber scaffolds, with their structural and compositional similarities to the natural extracellular matrix, serve as an effective substrate for fibroblast adhesion, proliferation, and migration. This review comprehensively summarizes the biological behavior of fibroblasts in DFUs and the mechanism mediating wound healing. At the same time, the mechanism of biological materials, especially electrospun nanofiber scaffolds, to improve the therapeutic effect by regulating the activity of fibroblasts was also discussed. By highlighting the latest advancements and clinical applications, we aim to provide a clear perspective on the future direction of DFU treatment strategies centered on fibroblast-targeted therapies.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"9 1","pages":"011501"},"PeriodicalIF":6.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543727","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":"Epigenetic dynamics in meniscus cell migration and its zonal dependency in response to inflammatory conditions.","authors":"Yize Zhang, Ellen Y Zhang, Catherine Cheung, Yuna Heo, Bat-Ider Tumenbayar, Se-Hwan Lee, Yongho Bae, Su Chin Heo","doi":"10.1063/5.0239035","DOIUrl":"10.1063/5.0239035","url":null,"abstract":"<p><p>Meniscus injuries are challenging to treat due to the tissue heterogeneity and limited treatment efficacy. Understanding meniscus cell migration, crucial for healing, remains incomplete, especially its zonal dependency. This study explores how epigenetic mechanisms affect meniscus cell migration under inflammation, focusing on healing implications. Distinct histone modifications and chromatin dynamics between inner and outer cells were observed during migration, emphasizing the need to consider these differences in repair strategies. Furthermore, tumor necrosis factor alpha (TNF-α), a proinflammatory cytokine, slows inner meniscus cell migration, while outer cells remain unaffected, indicating a zonal response. Interestingly, TNF-α differentially alters histone modifications, particularly H3K27me3, between the cell types. Transcriptome analysis showed significant gene expression changes with inner cells more affected than outer cells. Gene cluster analysis revealed different responses in chromatin remodeling, extracellular matrix assembly, and wound healing between zones. We further identified potential therapeutic targets by using epigenetic drugs, GSKJ4 (a histone demethylase inhibitor) and C646 (a histone acetyltransferase inhibitor), which restored inner meniscus cell migration under inflammatory conditions, highlighting their potential in treating meniscus tears. This highlights their potential utility in treating meniscus tear injuries. Overall, our findings elucidate the intricate interplay between epigenetic mechanisms and meniscus cell migration, along with its meniscus zonal dependency. This study provides insight into potential targets for enhancing meniscus repair and regeneration, which may lead to improved clinical outcomes for patients with meniscus injuries and osteoarthritis.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"9 1","pages":"016109"},"PeriodicalIF":6.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558329","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":"Analgesic effect of simultaneously targeting multiple pain processing brain circuits in an aged humanized mouse model of chronic pain by transcranial focused ultrasound.","authors":"Min Gon Kim, Chih-Yu Yeh, Kai Yu, Zherui Li, Kalpna Gupta, Bin He","doi":"10.1063/5.0236108","DOIUrl":"10.1063/5.0236108","url":null,"abstract":"<p><p>Low-intensity transcranial focused ultrasound (tFUS) has recently been shown to noninvasively and non-pharmacologically modulate pain hypersensitivity with high spatial specificity and deep brain penetration. However, the lack of knowledge about its effectiveness for pain management in older subjects vulnerable to severe pain who are also at increased risk of cognitive impairment, presents significant challenges. Additionally, current opioid pain treatments require hospital visits, limiting unwanted serious side effects with multiple liabilities, and device-based pain treatments are typically administered at medical facilities with bulky and expensive equipment, limiting accessibility and thus highlighting the need for at-home non-pharmacological treatment options. Here, we present a more accessible, noninvasive tFUS pain treatment strategy for senior subjects. This approach involves simultaneously targeting multiple pain-processing circuits using a battery-powered, compact, and low-cost ultrasound analog front end (UAFE). We developed and evaluated the performance of the UAFE capable of generating sufficiently high-amplitude output with significantly lower noise levels compared to a commercial transmitter. Using a humanized sickle mouse model of chronic hyperalgesia, we found that tFUS stimulation targeting multiple pain-processing circuits effectively reduces heat hyperalgesia in aged female mice. In addition to its efficacy, our behavioral-based safety assessment revealed no adverse effects on motor functions. These results suggest that using a battery-powered, compact UAFE to simultaneously target multiple pain-processing circuits can effectively suppress heat pain-related behaviors in aged female sickle mice without negatively impacting motor coordination and balance. This highlights the potential for further development of fully home-based tFUS pain treatment for seniors.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"9 1","pages":"016108"},"PeriodicalIF":4.9,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484226","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":"Polyploidy of MDA-MB-231 cells drives increased extravasation with enhanced cell-matrix adhesion.","authors":"Satomi Hirose, Tatsuya Osaki, Roger D Kamm","doi":"10.1063/5.0233329","DOIUrl":"10.1063/5.0233329","url":null,"abstract":"<p><p>Metastasis, the leading cause of cancer-related deaths, involves a complex cascade of events, including extravasation. Despite extensive research into metastasis, the mechanisms underlying extravasation remain unclear. Molecular targeted therapies have advanced cancer treatment, yet their efficacy is limited, prompting exploration into novel therapeutic targets. Here, we showed the association of polyploidy in MDA-MB-231 breast cancer cells and their extravasation, using microfluidic systems to reproduce the <i>in vivo</i> microvascular environment. We observed enhanced extravasation in polyploid cells alongside upregulated expression of genes involved in cell-substrate adhesion and cell mechanical dynamics. These findings offer insights into the relationship between polyploidy and extravasation, highlighting potential targets for cancer therapy.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"9 1","pages":"016105"},"PeriodicalIF":4.9,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11836873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143460141","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":"Stem cell mechanoadaptation. I. Effect of microtubule stabilization and volume changing stresses on cytoskeletal remodeling.","authors":"Vina D L Putra, Kristopher A Kilian, Melissa L Knothe Tate","doi":"10.1063/5.0231273","DOIUrl":"10.1063/5.0231273","url":null,"abstract":"<p><p>Here, we report on the first part of a two-part experimental series to elucidate spatiotemporal cytoskeletal remodeling, which underpins the evolution of stem cell shape and fate, and the emergence of tissue structure and function. In Part I of these studies, we first develop protocols to stabilize microtubules exogenously using paclitaxel (PAX) in a standardized model murine embryonic stem cell line (C3H/10T1/2) to maximize comparability with previously published studies. We then probe native and microtubule-stabilized stem cells' capacity to adapt to volume changing stresses effected by seeding at increasing cell densities, which emulates local compression and tissue template formation during development. Within the concentration range of 1-100 nM, microtubule-stabilized stem cells maintain viability and reduce proliferation. PAX stabilization of microtubules is associated with increased cell volume as well as flattening of the cell and nucleus. Compared to control cells, microtubule-stabilized cells exhibit thick, bundled microtubules and highly aligned, thicker and longer F-actin fibers, corresponding to an increase in the Young's modulus of the cell. Both F-actin and microtubule concentration increase with increasing PAX concentration, whereby the increase in F-actin is more prominent in the basal region of the cell. The corresponding increase in microtubule is observed more globally across the apical and basal region of the cell. Seeding at increasing target densities induces local compression on cells. This increase in local compression modulates cell volume and concomitant increases in F-actin and microtubule concentration to a greater degree than microtubule stabilization via PAX. Cells seeded at high density exhibit higher bulk modulus than corresponding cells seeded at low density. These data demonstrate the capacity of stem cells to adapt to an interplay of mechanical and chemical cues, i.e., respective compression and exogenous microtubule stabilization; the resulting cytoskeletal remodeling manifests as evolution of mechanical properties relevant to development of multicellular tissue constructs.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"9 1","pages":"016102"},"PeriodicalIF":4.9,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11719676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972598","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":"Organs-on-chips: Advanced engineered living systems.","authors":"Yi Liu, Liming Bian","doi":"10.1063/5.0250720","DOIUrl":"10.1063/5.0250720","url":null,"abstract":"","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 4","pages":"040401"},"PeriodicalIF":4.9,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11681975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903812","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":"Contractile responses of engineered human <i>μ</i>myometrium to prostaglandins and inflammatory cytokines.","authors":"Antonina P Maxey, Sage J Wheeler, Jaya M Travis, Megan L McCain","doi":"10.1063/5.0233737","DOIUrl":"10.1063/5.0233737","url":null,"abstract":"<p><p>Preterm labor is a prevalent public health problem and occurs when the myometrium, the smooth muscle layer of the uterus, begins contracting before the fetus reaches full term. Abnormal contractions of the myometrium also underlie painful menstrual cramps, known as dysmenorrhea. Both disorders have been associated with increased production of prostaglandins and cytokines, yet the functional impacts of inflammatory mediators on the contractility of human myometrium have not been fully established, in part due to a lack of effective model systems. To address this, we engineered human myometrial microtissues (<i>μ</i>myometrium) on compliant hydrogels designed for traction force microscopy. We then measured <i>μ</i>myometrium contractility in response to a panel of compounds with known contractile effects and inflammatory mediators. We observed that prostaglandin F2α, interleukin 6, and interleukin 8 induced contraction, while prostaglandin E1 and prostaglandin E2 induced relaxation. Our data suggest that inflammation may be a key factor modulating uterine contractility in conditions including, but not limited to, preterm labor or dysmenorrhea. More broadly, our <i>μ</i>myometrium model can be used to systematically identify the functional impact of many small molecules on human myometrium.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 4","pages":"046115"},"PeriodicalIF":6.6,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903811","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":"Immunogenic cell death-related cancer-associated fibroblast clusters and prognostic risk model in cervical cancer.","authors":"Fei Wu, Yue Xu","doi":"10.1063/5.0240772","DOIUrl":"10.1063/5.0240772","url":null,"abstract":"<p><p>Cervical cancer (CC) remains a leading cause of female cancer mortality globally. Immunogenic cell death (ICD) influences the tumor microenvironment (TME) and adaptive immune responses. Cancer-associated fibroblasts (CAFs) within the TME suppress anti-tumor immunity and contribute to CC progression. This study identified three ICD-related CAF clusters linked to patient survival, including IL6+CAF and ILR1+CAF, which were associated with clinical outcomes. Using a nine-gene risk model, patients were stratified into risk groups, with high-risk individuals showing worse survival and correlations with pathways such as hypoxia and TGFβ. The model also predicted immunotherapy responses, highlighting immune infiltration differences across risk groups. These findings provide insights into the role of CAF clusters in CC and present a risk model that supports prognosis prediction and personalized therapy.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 4","pages":"046114"},"PeriodicalIF":6.6,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11650426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847971","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}