Bioengineering & Translational Medicine最新文献

{"title":"The hanging-heart chip: A portable microfluidic device for high-throughput generation of contractile embryonic stem cell-derived cardiac spheroids","authors":"Pei-Tzu Lai,&nbsp;Cheng-Kun He,&nbsp;Chi-Han Li,&nbsp;Jefunnie Matahum,&nbsp;Chia-Yu Tang,&nbsp;Chia-Hsien Hsu","doi":"10.1002/btm2.10726","DOIUrl":"10.1002/btm2.10726","url":null,"abstract":"<p>Stem cell-derived cardiac spheroids are promising models for cardiac research and drug testing. However, generating contracting cardiac spheroids remains challenging because of the laborious experimental procedure. Here, we present a microfluidic hanging-heart chip (HH-chip) that uses a microchannel and flow-driven system to facilitate cell loading and culture medium replacement operations to reduce the laborious manual handling involved in the generation of a large quantity of cardiac spheroids. The effectiveness of the HH-chip was demonstrated by simultaneously forming 50 mouse embryonic stem cell-derived embryonic bodies, which sequentially differentiated into 90% beating cardiac spheroids within 15 days of culture on the chip. A comparison of our HH-chip method with traditional hanging-drop and low-attachment plate methods revealed that the HH-chip could generate higher contracting proportions of cardiac spheroids with higher expression of cardiac markers. Additionally, we verified that the contraction frequencies of the cardiac spheroids generated from the HH-chip were sensitive to cardiotoxic drugs. Overall, our results suggest that the microfluidic hanging drop chip-based approach is a high-throughput and highly efficient method for generating contracting mouse embryonic stem cell-derived cardiac spheroids for cardiac toxicity and drug testing applications.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 3","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10726","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142385478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiovascular patches applied in congenital cardiac surgery: Current materials and prospects","authors":"Mingze Sun,&nbsp;Vincent Reed LaSala,&nbsp;Caroline Giuglaris,&nbsp;David Blitzer,&nbsp;Sophia Jackman,&nbsp;Senay Ustunel,&nbsp;Kavya Rajesh,&nbsp;David Kalfa","doi":"10.1002/btm2.10706","DOIUrl":"10.1002/btm2.10706","url":null,"abstract":"<p>Congenital Heart Defects (CHDs) are the most common congenital anomalies, affecting between 4 and 75 per 1000 live births. Cardiovascular patches (CVPs) are frequently used as part of the surgical armamentarium to reconstruct cardiovascular structures to correct CHDs in pediatric patients. This review aims to evaluate the history of cardiovascular patches, currently available options, clinical applications, and important features of these patches. Performance and outcomes of different patch materials are assessed to provide reference points for clinicians. The target audience includes clinicians seeking data on clinical performance as they make choices between different patch products, as well as scientists and engineers working to develop patches or synthesize new patch materials.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10706","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142360302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A CRISPR mediated point-of-care assay for the detection of mucosal calprotectin in an animal model of ulcerative colitis","authors":"Selena Chia,&nbsp;Tianruo Guo,&nbsp;Ewa M. Goldys,&nbsp;Sophie C. Payne,&nbsp;Wenlu Duan,&nbsp;Nigel H. Lovell,&nbsp;Mohit N. Shivdasani,&nbsp;Fei Deng","doi":"10.1002/btm2.10725","DOIUrl":"10.1002/btm2.10725","url":null,"abstract":"<p>Inflammatory bowel disease (IBD) is a chronic disorder associated with inflammation in the gastrointestinal tract, leading to a range of debilitating symptoms. Fecal calprotectin is an established biomarker for ulcerative colitis (UC), one of the main IBD diseases, which provides indications of the presence and severity of inflammation in the digestive tract. Enzyme-Linked Immunosorbent Assay (ELISA) as a gold standard approach for fecal calprotectin detection is time-consuming and impractical in point-of-care settings. Moreover, obtaining fecal samples from patients is challenging and inhibits longitudinal monitoring. To address these specific problems, we have developed a novel approach for detecting calprotectin which leverages clustered regularly interspaced short palindromic repeats (CRISPR)/Cas technology. We successfully developed a portable tube-based CRISPR/Cas assay for point-of-care testing of calprotectin. This assay showed a detection range from 1 to 10,000 ng/ml (over 4 log units), using both fluorescent and colorimetric analytical techniques. The established assay was further validated through measurements in mucosal samples obtained in an anesthetised preclinical rodent model of UC, with 2–3 times higher calprotectin concentration detected in UC rat samples compared to that of healthy control animals. This point-of-care test may provide a rapid, precise, and user-friendly approach for the diagnosis and monitoring of IBD through mucosal sample testing.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 2","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10725","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142321313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel cytoprotective organ perfusion platform for reconstructing homeostasis of DCD liver while alleviating IRI injury","authors":"Tingting Lan,&nbsp;Mingxing Yu,&nbsp;Tao Ming,&nbsp;Hong Wang,&nbsp;Juan Deng,&nbsp;Shuhan Cheng,&nbsp;Zhongyang Shen,&nbsp;Deling Kong","doi":"10.1002/btm2.10724","DOIUrl":"10.1002/btm2.10724","url":null,"abstract":"<p>Pump is a vital component for expelling the perfusate in small animal isolated organ normothermic machine perfusion (NMP) systems whose flexible structure and rhythmic contraction play a crucial role in maintaining perfusion system homeostasis. However, the continuous extrusion forming with the rigid stationary shaft of the peristaltic pumps can damage cells, leading to metabolic disorders and eventual dysfunction of transplanted organs. Here, we developed a novel biomimetic blood-gas system (BBGs) for preventing cell damage. This system mimics the cardiac cycle and features an adjustable inspiratory-to-expiratory (IE) ratio to mitigate acidosis caused by continuous oxygen inhalation. In our study, adipose stem cells (ADSCs) were cultured within the circulatory system for 10 min, 2, and 4 h. Compared to the peristaltic pump, the BBGs significantly reduced cell apoptosis and morphological injury while enhancing cell proliferation and adhesion. Additionally, when the supernatant from ADSCs was introduced to LPS-induced macrophages for 24 h, the BBGs group demonstrated a more pronounced anti-inflammatory effect, characterized by reduced M1 macrophage expression. Besides, with isolated rat livers from donation after circulatory death (DCD) perfusion with ADSCs for 6 h by the BBGs, we detected fewer apoptotic cells and a reduced inflammatory response, evidenced by down-regulated TNF-α expression. The development of BBGs demonstrates the feasibility of recreating physiological liquid–gas circulation in vitro, offering an alternative platform for isolated organ perfusion, especially for applications involving cell therapy.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10724","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophages overexpressing interleukin-10 target and prevent atherosclerosis: Regression of plaque formation and reduction in necrotic core","authors":"Mingyi Wang,&nbsp;Shanshan Zhou,&nbsp;Yingyun Hu,&nbsp;Wei Tong,&nbsp;Hao Zhou,&nbsp;Mingrui Ma,&nbsp;Xingxuan Cai,&nbsp;Zhengbin Zhang,&nbsp;Luo Zhang,&nbsp;Yundai Chen","doi":"10.1002/btm2.10717","DOIUrl":"10.1002/btm2.10717","url":null,"abstract":"<p>Atherosclerosis, a slowly progressing inflammatory disease, is characterized by the presence of monocyte-derived macrophages. Interventions targeting the inflammatory characteristics of atherosclerosis hold promising potential. Although interleukin (IL)-10 is widely acknowledged for its anti-inflammatory effects, systemic administration of IL-10 has limitations due to its short half-life and significant systemic side effects. In this study, we aimed to investigate the effectiveness of an approach designed to overexpress IL-10 in macrophages and subsequently introduce these genetically modified cells into ApoE^−/− mice to promote atherosclerosis regression. We engineered RAW264.7 cells to overexpress IL-10 (referred to as IL-10M) using lentivirus vectors. The IL-10M exhibited robust IL-10 secretion, maintained phagocytic function, improved mitochondrial membrane potentials, reduced superoxide production and showed a tendency toward the M2 phenotype when exposed to inflammatory stimuli. IL-10M can selectively target plaques in ApoE^−/− mice and has the potential to reduce plaque area and necrotic core at both early and late stages of plaque progression. Moreover, there was a significant reduction in MMP9, a biomarker associated with plaque rupture, in IL-10M-treated plaques from both the early and late intervention groups. Additionally, the administration of IL-10M showed no obvious side effects. This study serves as proof that cell therapy based on anti-inflammatory macrophages might be a promising strategy for the intervention of atherosclerosis.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10717","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Self-assembly of PEG–PPS polymers and LL-37 peptide nanomicelles improves the oxidative microenvironment and promotes angiogenesis to facilitate chronic wound healing”","authors":"","doi":"10.1002/btm2.10718","DOIUrl":"10.1002/btm2.10718","url":null,"abstract":"<p>Shi R, Qiao J, Sun Q, Hou B, Li B, Zheng J, Zhang Z, Peng Z, Zhou J, Shen B, Deng J, Zhang X. Self-assembly of PEG–PPS polymers and LL-37 peptide nanomicelles improves the oxidative microenvironment and promotes angiogenesis to facilitate chronic wound healing. <i>Bioeng Transl Med</i>. 2023;9(2):e10619. doi:10.1002/btm2.10619</p><p>The authors regret some errors have been found in Figure 5, Figure S12, and Figure S15.</p><p>In Figure 5, due to the misuse of wound images of the LL-37@PEG–PPS group on day 9, there was a duplication with the wound images of the PEG–PPS group on day 11.</p><p>In Figure S12a, due to misuse of images, there was partial overlap of the 0 h images between the control group and PEG–PPS group.</p><p>In Figure S15a, unintentional misuse of the in vivo biodistribution image of FITC-LL-37@PEG–PPS in before injection group, which leads to an overlapped with that on day 4.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"9 6","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10718","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142160534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A stretchable human lung-on-chip model of alveolar inflammation for evaluating anti-inflammatory drug response","authors":"Clémentine Richter,&nbsp;Lorenz Latta,&nbsp;Daria Harig,&nbsp;Patrick Carius,&nbsp;Janick D. Stucki,&nbsp;Nina Hobi,&nbsp;Andreas Hugi,&nbsp;Paul Schumacher,&nbsp;Tobias Krebs,&nbsp;Alexander Gamrekeli,&nbsp;Felix Stöckle,&nbsp;Klaus Urbschat,&nbsp;Galia Montalvo,&nbsp;Franziska Lautenschläger,&nbsp;Brigitta Loretz,&nbsp;Alberto Hidalgo,&nbsp;Nicole Schneider-Daum,&nbsp;Claus-Michael Lehr","doi":"10.1002/btm2.10715","DOIUrl":"10.1002/btm2.10715","url":null,"abstract":"<p>This study describes a complex human in vitro model for evaluating anti-inflammatory drug response in the alveoli that may contribute to the reduction of animal testing in the pre-clinical stage of drug development. The model is based on the human alveolar epithelial cell line Arlo co-cultured with macrophages differentiated from the THP-1 cell line, creating a physiological biological microenvironment. To mimic the three-dimensional architecture and dynamic expansion and relaxation of the air-blood-barrier, they are grown on a stretchable microphysiological lung-on-chip. For validating the in vitro model, three different protocols have been developed to demonstrate the clinically established anti-inflammatory effect of glucocorticoids to reduce certain inflammatory markers after different pro-inflammatory stimuli: (1) an inflammation caused by bacterial LPS (lipopolysaccharides) to simulate an LPS-induced acute lung injury measured best with cytokine IL-6 release; (2) an inflammation caused by LPS at ALI (air-liquid interface) to investigate aerosolized anti-inflammatory treatment, measured with chemokine IL-8 release; and (3) an inflammation with a combination of human inflammatory cytokines TNFα and IFNγ to simulate a critical cytokine storm leading to epithelial barrier disruption, where the eventual weakening or protection of the epithelial barrier can be measured. In all cases, the presence of macrophages appeared to be crucial to mediating inflammatory changes in the alveolar epithelium. LPS induction led to inflammatory changes independently of stretch conditions. Dynamic stretch, emulating breathing-like mechanics, was essential for in vitro modeling of the clinically relevant outcome of epithelial barrier disruption upon TNFα/IFNγ-induced inflammation.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10715","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Doxorubicin-loaded nanoparticle coated with endothelial cells-derived exosomes for immunogenic chemotherapy of glioblastoma”","authors":"","doi":"10.1002/btm2.10719","DOIUrl":"10.1002/btm2.10719","url":null,"abstract":"<p>Zhang C, Song J, Lou L, et al. Doxorubicin-loaded nanoparticle coated with endothelial cells-derived exosomes for immunogenic chemotherapy of glioblastoma. Bioeng Transl Med 2020;6(3):e10203.</p><p>We apologize for this error.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"9 6","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10719","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elucidating the role of carrier proteins in cytokine stabilization within double emulsion-based polymeric nanoparticles","authors":"Emily R. Rhodes,&nbsp;Nicole B. Day,&nbsp;Emma C. Aldrich,&nbsp;C. Wyatt Shields IV,&nbsp;Kayla G. Sprenger","doi":"10.1002/btm2.10722","DOIUrl":"10.1002/btm2.10722","url":null,"abstract":"<p>Polymeric micro- and nanoparticles are useful vehicles for delivering cytokines to diseased tissues such as solid tumors. Double emulsion solvent evaporation is one of the most common techniques to formulate cytokines into vehicles made from hydrophobic polymers; however, the liquid–liquid interfaces formed during emulsification can greatly affect the stability and therapeutic performance of encapsulated cytokines. To develop more effective cytokine-delivery systems, a clear molecular understanding of the interactions between relevant proteins and solvents used in the preparation of such particles is needed. We utilized an integrated computational and experimental approach for studying the governing mechanisms by which interleukin-12 (IL-12), a clinically relevant cytokine, is protected from denaturation by albumin, a common stabilizing protein, at an organic-aqueous solvent interface formed during double emulsification. We investigated protein–protein interactions between human (h)IL-12 and albumin and simulated these components in pure water, dichloromethane (DCM), and along a water/DCM interface to replicate the solvent regimes formed during double emulsification. We observed that (i) hIL-12 experiences increased structural deviations near the water/DCM interface, and (ii) hIL-12 structural deviations are reduced in the presence of albumin. Experimentally, we found that hIL-12 bioactivity is retained when released from particles in which albumin is added to the aqueous phase in molar excess to hIL-12 and sufficient time is allowed for albumin-hIL-12 binding. Findings from this work have implications in establishing design principles to enhance the stability of cytokines and other unstable proteins in particles formed by double emulsification for improved stability and therapeutic efficacy.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10722","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142144238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in bioengineered CAR T/NK cell therapy for glioblastoma: Overcoming immunosuppression and nanotechnology-based strategies for enhanced CAR T/NK cell therapy","authors":"Nasim Dana,&nbsp;Arezou Dabiri,&nbsp;Majed Bahri Najafi,&nbsp;Azadeh Rahimi,&nbsp;Sayed Mohammad Matin Ishaghi,&nbsp;Laleh Shariati,&nbsp;Minmin Shao,&nbsp;Assunta Borzacchiello,&nbsp;Ilnaz Rahimmanesh,&nbsp;Pooyan Makvandi","doi":"10.1002/btm2.10716","DOIUrl":"10.1002/btm2.10716","url":null,"abstract":"<p>Glioblastoma is a strong challenge in the worldwide field of central nervous system malignancies. GBM's inherent heterogeneity, along with the formation of an immunosuppressive tumor microenvironment, supports its resistance to current therapy methods. Immunotherapeutic methods have emerged as potential options in recent years. However, because of the inherent limits of traditional immunotherapeutic techniques innovative approaches are required. Advances in cut-edge techniques provide a possible route for improving effector cell effectiveness. This review gives insight into the complicated immunosuppressive pathways in GBM, with a particular emphasis on CAR T/NK-cell treatment as a potential achievement. Recognizing and addressing these concerns might open the way for more effective and focused glioblastoma therapies, providing hope for the future with the aim of improved outcomes for patients. In addition, this review presents valuable insights into the integration of nanotechnology into CAR T/NK cell therapy for enhanced efficiency of these personalized gene therapy products.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 2","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10716","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}