APL Bioengineering最新文献

{"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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}

{"title":"Single-pericyte nanomechanics measured by contraction cytometry.","authors":"Md Mydul Islam, Ignas Gaska, Oluwamayokun Oshinowo, Adiya Otumala, Shashank Shekhar, Nicholas Au Yong, David R Myers","doi":"10.1063/5.0213761","DOIUrl":"10.1063/5.0213761","url":null,"abstract":"<p><p>Pericytes line the microvasculature throughout the body and play a key role in regulating blood flow by constricting and dilating vessels. However, the biophysical mechanisms through which pericytes transduce microenvironmental chemical and mechanical cues to mediate vessel diameter, thereby impacting oxygen and nutrient delivery, remain largely unknown. This knowledge gap is clinically relevant as numerous diseases are associated with the aberrant contraction of pericytes, which are unusually susceptible to injury. Here, we report the development of a high-throughput hydrogel-based pericyte contraction cytometer that quantifies single-cell contraction forces from murine and human pericytes in different microvascular microenvironments and in the presence of competing vasoconstricting and vasodilating stimuli. We further show that murine pericyte survival in hypoxia is mediated by the mechanical microenvironment and that, paradoxically, pre-treating pericytes to reduce contraction increases hypoxic cell death. Moreover, using the contraction cytometer as a drug-screening tool, we found that cofilin-1 could be applied extracellularly to release murine pericytes from hypoxia-induced contractile <i>rigor mortis</i> and, therefore, may represent a novel approach for mitigating the long-lasting decrease in blood flow that occurs after hypoxic injury.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11316606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141917742","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":"Exploring the translational impact of type 1 diabetes on cerebral neurovascular function through ECoG-LSCI","authors":"Shaoyu Yen, Yuhling Wang, Lun-De Liao","doi":"10.1063/5.0193267","DOIUrl":"https://doi.org/10.1063/5.0193267","url":null,"abstract":"Type 1 diabetes mellitus (T1DM) can result in complications such as retinopathy, nephropathy, and peripheral neuropathy, which can lead to brain dysfunction. In this study, we investigated the effects of T1DM on cerebral neurovascular function in mice. Streptozotocin (STZ) is known to induce T1DM in animals; thus, we used an STZ-induced diabetes model to evaluate the effects of hyperglycemia on brain morphology and neurovascular tissue. Neurovascular coupling is the connection between neuronal activity and cerebral blood flow that maintains brain function. The ECoG-LSCI technique combines electrocorticography (ECoG) and laser speckle contrast imaging (LSCI) to detect cortical spreading depression (CSD) as a marker of neurovascular coupling and measure corresponding neurovascular function. Our results suggested that in the STZ group, hyperglycemia affected excitatory neurotransmission and metabolism, leading to reductions in intercellular signaling, somatosensory evoked potential (SSEP) amplitudes, and CSD transmission rates. Western blot data further revealed that brain-derived neurotrophic factor (BDNF) and neuronal nuclear antigen levels were reduced in the STZ group. Abnormalities in glucose metabolism in the brain and increased phosphorylation of AKT and GSK3 are hypothesized to be responsible for these decreases. Overall, this study highlights the importance of glucose metabolism in normal brain physiology and demonstrates that hyperglycemia disrupts neurovascular coupling and affects cerebral neurovascular function and that the degree of CSD is positively correlated with the extent of brain tissue damage. Further research is essential to gain a complete understanding of the related mechanisms and the implications of these findings.","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141927323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three-dimensional matrix stiffness modulates mechanosensitive and phenotypic alterations in oral squamous cell carcinoma spheroids.","authors":"Maulee Sheth, Manju Sharma, Maria Lehn, HasanAl Reza, Takanori Takebe, Vinita Takiar, Trisha Wise-Draper, Leyla Esfandiari","doi":"10.1063/5.0210134","DOIUrl":"10.1063/5.0210134","url":null,"abstract":"<p><p>Extracellular biophysical cues such as matrix stiffness are key stimuli tuning cell fate and affecting tumor progression <i>in vivo</i>. However, it remains unclear how cancer spheroids in a 3D microenvironment perceive matrix mechanical stiffness stimuli and translate them into intracellular signals driving progression. Mechanosensitive Piezo1 and TRPV4 ion channels, upregulated in many malignancies, are major transducers of such physical stimuli into biochemical responses. Most mechanotransduction studies probing the reception of changing stiffness cues by cells are, however, still limited to 2D culture systems or cell-extracellular matrix models, which lack the major cell-cell interactions prevalent in 3D cancer tumors. Here, we engineered a 3D spheroid culture environment with varying mechanobiological properties to study the effect of static matrix stiffness stimuli on mechanosensitive and malignant phenotypes in oral squamous cell carcinoma spheroids. We find that spheroid growth is enhanced when cultured in stiff extracellular matrix. We show that the protein expression of mechanoreceptor Piezo1 and stemness marker CD44 is upregulated in stiff matrix. We also report the upregulation of a selection of genes with associations to mechanoreception, ion channel transport, extracellular matrix organization, and tumorigenic phenotypes in stiff matrix spheroids. Together, our results indicate that cancer cells in 3D spheroids utilize mechanosensitive ion channels Piezo1 and TRPV4 as means to sense changes in static extracellular matrix stiffness, and that stiffness drives pro-tumorigenic phenotypes in oral squamous cell carcinoma.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11293878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876298","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":"CAR T cell infiltration and cytotoxic killing within the core of 3D breast cancer spheroids under the control of antigen sensing in microwell arrays.","authors":"Youngbin Cho, Matthew S Laird, Teddi Bishop, Ruxuan Li, Dorota E Jazwinska, Elisa Ruffo, Jason Lohmueller, Ioannis K Zervantonakis","doi":"10.1063/5.0207941","DOIUrl":"10.1063/5.0207941","url":null,"abstract":"<p><p>The success of chimeric antigen receptor (CAR) T cells in blood cancers has intensified efforts to develop CAR T therapies for solid cancers. In the solid tumor microenvironment, CAR T cell trafficking and suppression of cytotoxic killing represent limiting factors for therapeutic efficacy. Here, we present a microwell platform to study CAR T cell interactions with 3D breast tumor spheroids and determine predictors of anti-tumor CAR T cell function. To precisely control antigen sensing, we utilized a switchable adaptor CAR system that covalently attaches to co-administered antibody adaptors and mediates antigen recognition. Following the addition of an anti-HER2 adaptor antibody, primary human CAR T cells exhibited higher infiltration, clustering, and secretion of effector cytokines. By tracking CAR T cell killing in individual spheroids, we showed the suppressive effects of spheroid size and identified the initial CAR T cell to spheroid area ratio as a predictor of cytotoxicity. We demonstrate that larger spheroids exhibit higher hypoxia levels and are infiltrated by CAR T cells with a suppressed activation state, characterized by reduced expression of IFN-γ, TNF-α, and granzyme B. Spatiotemporal analysis revealed lower CAR T cell numbers and cytotoxicity in the spheroid core compared to the periphery. Finally, increasing CAR T cell seeding density resulted in higher CAR T cell infiltration and cancer cell elimination in the spheroid core. Our findings provide new quantitative insight into CAR T cell function within 3D cancer spheroids. Given its miniaturized nature and live imaging capabilities, our microfabricated system holds promise for screening cellular immunotherapies.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11268919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141761607","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":"Mutual antagonism between CD44 and integrins in glioblastoma cell traction and migration.","authors":"Marcus D Kelly, Matthew R Pawlak, Kevin H Zhan, Ghaidan A Shamsan, Wendy R Gordon, David J Odde","doi":"10.1063/5.0203028","DOIUrl":"10.1063/5.0203028","url":null,"abstract":"<p><p>Cell migration is the major driver of invasion and metastasis during cancer progression. For cells to migrate, they utilize the actin-myosin cytoskeleton and adhesion molecules, such as integrins and CD44, to generate traction forces in their environment. CD44 primarily binds to hyaluronic acid (HA) and integrins primarily bind to extracellular matrix (ECM) proteins such as collagen. However, the role of CD44 under integrin-mediated conditions and vice versa is not well known. Here, we performed traction force microscopy (TFM) on U251 cells seeded on collagen I-coated polyacrylamide gels to assess the functional mechanical relationship between integrins and CD44. Performing TFM on integrin-mediated adhesion conditions, i.e., collagen, we found that CD44KO U251 cells exerted more traction force than wild-type (WT) U251 cells. Furthermore, untreated WT and CD44-blocked WT exhibited comparable results. Conversely, in CD44-mediated adhesive conditions, integrin-blocked WT cells exerted a higher traction force than untreated WT cells. Our data suggest that CD44 and integrins have a mutually antagonistic relationship where one receptor represses the other's ability to generate traction force on its cognate substrate.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11219079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141493927","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}