APL Bioengineering最新文献

{"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":"https://doi.org/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}

{"title":"Advancing hyperspectral imaging and machine learning tools toward clinical adoption in tissue diagnostics: A comprehensive review.","authors":"Chun-Liang Lai, Riya Karmakar, Arvind Mukundan, Ragul Kumar Natarajan, Song-Cun Lu, Cheng-Yi Wang, Hsiang-Chen Wang","doi":"10.1063/5.0240444","DOIUrl":"10.1063/5.0240444","url":null,"abstract":"<p><p>Hyperspectral imaging (HSI) has become an evident transformative apparatus in medical diagnostics. The review aims to appraise the present advancement and challenges in HSI for medical applications. It features a variety of medical applications namely diagnosing diabetic retinopathy, neurodegenerative diseases like Parkinson's and Alzheimer's, which illustrates its effectiveness in early diagnosis, early caries detection in periodontal disease, and dermatology by detecting skin cancer. Regardless of these advances, the challenges exist within every aspect that limits its broader clinical adoption. It has various constraints including difficulties with technology related to the complexity of the HSI system and needing specialist training, which may act as a drawback to its clinical settings. This article pertains to potential challenges expressed in medical applications and probable solutions to overcome these constraints. Successful companies that perform advanced solutions with HSI in terms of medical applications are being emphasized in this study to signal the high level of interest in medical diagnosis for systems to incorporate machine learning ML and artificial intelligence AI to foster precision diagnosis and standardized clinical workflow. This advancement signifies progressive possibilities of HSI in real-time clinical assessments. In conclusion despite HSI has been presented as a significant advanced medical imaging tool, addressing its limitations and probable solutions is for broader clinical adoption.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 4","pages":"041504"},"PeriodicalIF":6.6,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11629177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142808082","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":"On-chip fabrication of tailored 3D hydrogel scaffolds to model cancer cell invasion and interaction with endothelial cells.","authors":"Federico Cantoni, Laurent Barbe, Ananya Roy, Grzegorz Wicher, Stina Simonsson, Karin Forsberg-Nilsson, Maria Tenje","doi":"10.1063/5.0227135","DOIUrl":"10.1063/5.0227135","url":null,"abstract":"<p><p>The high mortality associated with certain cancers can be attributed to the invasive nature of the tumor cells. Yet, the complexity of studying invasion hinders our understanding of how the tumor spreads. This work presents a microengineered three-dimensional (3D) <i>in vitro</i> model for studying cancer cell invasion and interaction with endothelial cells. The model was generated by printing a biomimetic hydrogel scaffold directly on a chip using 2-photon polymerization that simulates the brain's extracellular matrix. The scaffold's geometry was specifically designed to facilitate the growth of a continuous layer of endothelial cells on one side, while also allowing for the introduction of tumor cells on the other side. This arrangement confines the cells spatially and enables <i>in situ</i> microscopy of the cancer cells as they invade the hydrogel scaffold and interact with the endothelial layer. We examined the impact of 3D printing parameters on the hydrogel's physical properties and used patient derived glioblastoma cells to study their effect on cell invasion. Notably, the tumor cells tended to infiltrate faster when an endothelial cell barrier was present. The potential for adjusting the hydrogel scaffold's properties, coupled with the capability for real-time observation of tumor-endothelial cell interactions, offers a platform for studying tumor invasion and tumor-endothelial cell interactions.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 4","pages":"046113"},"PeriodicalIF":6.6,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11617029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781301","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":"Geometrically engineered organoid units and their assembly for pre-construction of organ structures.","authors":"Ayaka Kadotani, Gen Hayase, Daisuke Yoshino","doi":"10.1063/5.0222866","DOIUrl":"10.1063/5.0222866","url":null,"abstract":"<p><p>Regenerative medicine is moving from the nascent to the transitional stage as researchers are actively engaged in creating mini-organs from pluripotent stem cells to construct artificial models of physiological and pathological conditions. Currently, mini-organs can express higher-order functions, but their size is limited to the order of a few millimeters. Therefore, one of the ultimate goals of regenerative medicine, \"organ replication and transplantation with organoid,\" remains a major obstacle. Three-dimensional (3D) bioprinting technology is expected to be an innovative breakthrough in this field, but various issues have been raised, such as cell damage, versatility of bioink, and printing time. In this study, we established a method for fabricating, connecting, and assembling organoid units of various shapes independent of cell type, extracellular matrix, and adhesive composition (unit construction method). We also fabricated kidney tissue-like structures using three types of parenchymal and interstitial cells that compose the human kidney and obtained findings suggesting the possibility of crosstalk between the units. This study mainly focuses on methods for reproducing the structure of organs, and there are still issues to be addressed in terms of the expression of their higher-order functions. We anticipate that engineering innovation based on this technique will bring us closer to the realization of highly efficient and rapid fabrication of full-scale organoids that can withstand organ transplantation.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 4","pages":"046112"},"PeriodicalIF":6.6,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11602216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142740925","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":"High cell throughput, programmable fixation reveals the RNA and protein co-regulation with spatially resolved NFκB pseudo-signaling.","authors":"Nicholas Zhang, Mingshuang Wang, Dhruv Nambiar, Samyukta Iyer, Priyam Kadakia, Qianqi Luo, Sicheng Pang, Aaron Qu, Nivik Sanjay Bharadwaj, Peng Qiu, Ahmet F Coskun","doi":"10.1063/5.0227054","DOIUrl":"10.1063/5.0227054","url":null,"abstract":"<p><p>RNA translation to protein is paramount to creating life, yet RNA and protein correlations vary widely across tissues, cells, and species. To investigate these perplexing results, we utilize a time-series fixation method that combines static stimulation and a programmable formaldehyde perfusion to map pseudo-Signaling with Omics signatures (pSigOmics) of single-cell data from hundreds of thousands of cells. Using the widely studied nuclear factor kappa B (NFκB) mammalian signaling pathway in mouse fibroblasts, we discovered a novel asynchronous pseudotime regulation (APR) between RNA and protein levels in the quintessential NFκB p65 protein using single molecule spatial imaging. Prototypical NFκB dynamics are successfully confirmed by the rise and fall of NFκB response as well as A20 negative inhibitor activity by 90 min. The observed p65 translational APR is evident in both statically sampled timepoints and dynamic response gradients from programmable formaldehyde fixation, which successfully creates continuous response measurements. Finally, we implement a graph neural network model capable of predicting APR cell subpopulations from GAPDH RNA spatial expression, which is strongly correlated with p65 RNA signatures. Successful decision tree classifiers on Potential of Heat-diffusion for Affinity-based Trajectory Embedding embeddings of our data, which illustrate partitions of APR cell subpopulations in latent space, further confirm the APR patterns. Together, our data suggest an RNA-protein regulatory framework in which translation adapts to signaling events and illuminates how immune signaling is timed across various cell subpopulations.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 4","pages":"046108"},"PeriodicalIF":6.6,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11601099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142740926","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":"Conducting polymer hydrogels for biomedical application: Current status and outstanding challenges.","authors":"Matthew S Horrocks, Kirill E Zhurenkov, Jenny Malmström","doi":"10.1063/5.0218251","DOIUrl":"https://doi.org/10.1063/5.0218251","url":null,"abstract":"<p><p>Conducting polymer hydrogels (CPHs) are composite polymeric materials with unique properties that combine the electrical capabilities of conducting polymers (CPs) with the excellent mechanical properties and biocompatibility of traditional hydrogels. This review aims to highlight how the unique properties CPHs have from combining their two constituent materials are utilized within the biomedical field. First, the synthesis approaches and applications of non-CPH conductive hydrogels are discussed briefly, contrasting CPH-based systems. The synthesis routes of hydrogels, CPs, and CPHs are then discussed. This review also provides a comprehensive overview of the recent advancements and applications of CPHs in the biomedical field, encompassing their applications as biosensors, drug delivery scaffolds (DDSs), and tissue engineering platforms. Regarding their applications within tissue engineering, a comprehensive discussion of the usage of CPHs for skeletal muscle prosthetics and regeneration, cardiac regeneration, epithelial regeneration and wound healing, bone and cartilage regeneration, and neural prosthetics and regeneration is provided. Finally, critical challenges and future perspectives are also addressed, emphasizing the need for continued research; however, this fascinating class of materials holds promise within the vastly evolving field of biomedicine.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 3","pages":"031503"},"PeriodicalIF":6.6,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11424142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142356135","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 novel stress sensor enables accurate estimation of micro-scale tissue mechanics in quantitative micro-elastography.","authors":"Kai L Metzner, Qi Fang, Rowan W Sanderson, Yen L Yeow, Celia Green, Farah Abdul-Aziz, Juliana Hamzah, Alireza Mowla, Brendan F Kennedy","doi":"10.1063/5.0220309","DOIUrl":"https://doi.org/10.1063/5.0220309","url":null,"abstract":"<p><p>Quantitative micro-elastography (QME) is a compression-based optical coherence elastography technique enabling the estimation of tissue mechanical properties on the micro-scale. QME utilizes a compliant layer as an optical stress sensor, placed between an imaging window and tissue, providing quantitative estimation of elasticity. However, the implementation of the layer is challenging and introduces unpredictable friction conditions at the contact boundaries, deteriorating the accuracy and reliability of elasticity estimation. This has largely limited the use of QME to <i>ex vivo</i> studies and is a barrier to clinical translation. In this work, we present a novel implementation by affixing the stress sensing layer to the imaging window and optimizing the layer thickness, enhancing the practical use of QME for <i>in vivo</i> applications by eliminating the requirement for manual placement of the layer, and significantly reducing variations in the friction conditions, leading to substantial improvement in the accuracy and repeatability of elasticity estimation. We performed a systematic validation of the integrated layer, demonstrating >30% improvement in sensitivity and the ability to provide mechanical contrast in a mechanically heterogeneous phantom. In addition, we demonstrate the ability to obtain accurate estimation of elasticity (<6% error compared to <14% achieved using existing QME) in homogeneous phantoms with mechanical properties ranging from 40 to 130 kPa. Furthermore, we show the integrated layer to be more robust, exhibiting increased temporal stability, as well as improved conformity to variations in sample surface topography, allowing for accurate estimation of elasticity over acquisition times 3× longer than current methods. Finally, when applied to <i>ex vivo</i> human breast tissue, we demonstrate the ability to distinguish between healthy and diseased tissue features, such as stroma and cancer, confirmed by co-registered histology, showcasing the potential for routine use in biomedical applications.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 3","pages":"036115"},"PeriodicalIF":6.6,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11421860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142356134","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 gene therapy combined with tissue engineering to promote bone regeneration.","authors":"Xiangyu Chu, Yuan Xiong, Li Lu, Yiqing Wang, Jing Wang, Ruiyin Zeng, Liangcong Hu, Chenchen Yan, Zhiming Zhao, Sien Lin, Bobin Mi, Guohui Liu","doi":"10.1063/5.0200551","DOIUrl":"https://doi.org/10.1063/5.0200551","url":null,"abstract":"<p><p>Gene therapy has emerged as a highly promising strategy for the clinical treatment of large segmental bone defects and non-union fractures, which is a common clinical need. Meanwhile, many preclinical data have demonstrated that gene and cell therapies combined with optimal scaffold biomaterials could be used to solve these tough issues. Bone tissue engineering, an interdisciplinary field combining cells, biomaterials, and molecules with stimulatory capability, provides promising alternatives to enhance bone regeneration. To deliver and localize growth factors and associated intracellular signaling components into the defect site, gene therapy strategies combined with bioengineering could achieve a uniform distribution and sustained release to ensure mesenchymal stem cell osteogenesis. In this review, we will describe the process and cell molecular changes during normal fracture healing, followed by the advantages and disadvantages of various gene therapy vectors combined with bone tissue engineering. The growth factors and other bioactive peptides in bone regeneration will be particularly discussed. Finally, gene-activated biomaterials for bone regeneration will be illustrated through a description of characteristics and synthetic methods.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 3","pages":"031502"},"PeriodicalIF":6.6,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11412735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142298283","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":"Rapid flowing cells localization enabled by spatiotemporal manipulation of their holographic patterns.","authors":"Zhengzhong Huang, Zhe Wang, Daniele Pirone, Vittorio Bianco, Lisa Miccio, Pasquale Memmolo, Liangcai Cao, Pietro Ferraro","doi":"10.1063/5.0222932","DOIUrl":"https://doi.org/10.1063/5.0222932","url":null,"abstract":"<p><p>Lab-on-a-Chip microfluidic devices present an innovative and cost-effective platform in the current trend of miniaturization and simplification of imaging flow cytometry; they are excellent candidates for high-throughput single-cell analysis. In such microfluidic platforms, cell tracking becomes a fundamental tool for investigating biophysical processes, from intracellular dynamics to the characterization of cell motility and migration. However, high-throughput and long-term cell tracking puts a high demand on the consumption of computing resources. Here, we propose a novel strategy to achieve rapid 3D cell localizations along the microfluidic channel. This method is based on the spatiotemporal manipulation of recorded holographic interference fringes, and it allows fast and precise localization of cells without performing complete holographic reconstruction. Conventional holographic tracking is typically based on the phase contrast obtained by decoupling the calculation of optical axial and transverse coordinates. Computing time and resource consumption may increase because all the frames need to be calculated in the Fourier domain. In our proposed method, the 2D transverse positions are directly located by morphological calculation based on the hologram. The complex-amplitude wavefronts are directly reconstructed by spatiotemporal phase shifting to calculate the axial position by the refocusing criterion. Only spatial calculation is considered in the proposed method. We demonstrate that the computational time of transverse tracking is only one-tenth of the conventional method, while the total computational time of the proposed method decreases up to 54% with respect to the conventional approach. The proposed approach can open the route for analyzing flow cytometry in quantitative phase microscopy assays.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 3","pages":"036114"},"PeriodicalIF":6.6,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11390135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142298282","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":"Multimodal mechano-microscopy reveals mechanical phenotypes of breast cancer spheroids in three dimensions.","authors":"Alireza Mowla, Matt S Hepburn, Jiayue Li, Danielle Vahala, Sebastian E Amos, Liisa M Hirvonen, Rowan W Sanderson, Philip Wijesinghe, Samuel Maher, Yu Suk Choi, Brendan F Kennedy","doi":"10.1063/5.0213077","DOIUrl":"https://doi.org/10.1063/5.0213077","url":null,"abstract":"<p><p>Cancer cell invasion relies on an equilibrium between cell deformability and the biophysical constraints imposed by the extracellular matrix (ECM). However, there is little consensus on the nature of the local biomechanical alterations in cancer cell dissemination in the context of three-dimensional (3D) tumor microenvironments (TMEs). While the shortcomings of two-dimensional (2D) models in replicating <i>in situ</i> cell behavior are well known, 3D TME models remain underutilized because contemporary mechanical quantification tools are limited to surface measurements. Here, we overcome this major challenge by quantifying local mechanics of cancer cell spheroids in 3D TMEs. We achieve this using multimodal mechano-microscopy, integrating optical coherence microscopy-based elasticity imaging with confocal fluorescence microscopy. We observe that non-metastatic cancer spheroids show no invasion while showing increased peripheral cell elasticity in both stiff and soft environments. Metastatic cancer spheroids, however, show ECM-mediated softening in a stiff microenvironment and, in a soft environment, initiate cell invasion with peripheral softening associated with early metastatic dissemination. This exemplar of live-cell 3D mechanotyping supports that invasion increases cell deformability in a 3D context, illustrating the power of multimodal mechano-microscopy for quantitative mechanobiology <i>in situ</i>.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 3","pages":"036113"},"PeriodicalIF":6.6,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11387014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142298281","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}