APL Bioengineering最新文献_第5页

Mechanoregulation of MSC spheroid immunomodulation. 间充质干细胞球体免疫调节的机制调节

IF 6 3区医学

APL Bioengineering Pub Date : 2024-03-01 DOI: 10.1063/5.0184431

Victoria L Thai, Sabrina Mierswa, Katherine H Griffin, Joel D Boerckel, J Kent Leach

{"title":"Mechanoregulation of MSC spheroid immunomodulation.","authors":"Victoria L Thai, Sabrina Mierswa, Katherine H Griffin, Joel D Boerckel, J Kent Leach","doi":"10.1063/5.0184431","DOIUrl":"10.1063/5.0184431","url":null,"abstract":"Mesenchymal stromal cells (MSCs) are widely used in cell-based therapies and tissue regeneration for their potent secretome, which promotes host cell recruitment and modulates inflammation. Compared to monodisperse cells, MSC spheroids exhibit improved viability and increased secretion of immunomodulatory cytokines. While mechanical stimulation of monodisperse cells can increase cytokine production, the influence of mechanical loading on MSC spheroids is unknown. Here, we evaluated the effect of controlled, uniaxial cyclic compression on the secretion of immunomodulatory cytokines by human MSC spheroids and tested the influence of load-induced gene expression on MSC mechanoresponsiveness. We exposed MSC spheroids, entrapped in alginate hydrogels, to three cyclic compressive regimes with varying stress (L) magnitudes (i.e., 5 and 10 kPa) and hold (H) durations (i.e., 30 and 250 s) L5H30, L10H30, and L10H250. We observed changes in cytokine and chemokine expression dependent on the loading regime, where higher stress regimes tended to result in more exaggerated changes. However, only MSC spheroids exposed to L10H30 induced human THP-1 macrophage polarization toward an M2 phenotype compared to static conditions. Static and L10H30 loading facilitated a strong, interlinked F-actin arrangement, while L5H30 and L10H250 disrupted the structure of actin filaments. This was further examined when the actin cytoskeleton was disrupted via Y-27632. We observed downregulation of YAP-related genes, and the levels of secreted inflammatory cytokines were globally decreased. These findings emphasize the essential role of mechanosignaling in mediating the immunomodulatory potential of MSC spheroids.","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 1","pages":"016116"},"PeriodicalIF":6.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10908560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140022891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In situ single-molecule investigations of the impacts of biochemical perturbations on conformational intermediates of monomeric α-synuclein. 原位单分子研究生化扰动对单体α-突触核蛋白构象中间产物的影响。

IF 6 3区医学

APL Bioengineering Pub Date : 2024-03-01 DOI: 10.1063/5.0188714

Wenmao Huang, Jingzhun Liu, Shimin Le, Mingxi Yao, Yi Shi, Jie Yan

{"title":"In situ single-molecule investigations of the impacts of biochemical perturbations on conformational intermediates of monomeric α-synuclein.","authors":"Wenmao Huang, Jingzhun Liu, Shimin Le, Mingxi Yao, Yi Shi, Jie Yan","doi":"10.1063/5.0188714","DOIUrl":"10.1063/5.0188714","url":null,"abstract":"α-Synuclein aggregation is a common trait in synucleinopathies, including Parkinson's disease. Being an unstructured protein, α-synuclein exists in several distinct conformational intermediates, contributing to both its function and pathogenesis. However, the regulation of these monomer conformations by biochemical factors and potential drugs has remained elusive. In this study, we devised an in situ single-molecule manipulation approach to pinpoint kinetically stable conformational intermediates of monomeric α-synuclein and explore the effects of various biochemical factors and drugs. We uncovered a partially folded conformation located in the non-amyloid-β component (NAC) region of monomeric α-synuclein, which is regulated by a preNAC region. This conformational intermediate is sensitive to biochemical perturbations and small-molecule drugs that influencing α-synuclein's aggregation tendency. Our findings reveal that this partially folded intermediate may play a role in α-synuclein aggregation, offering fresh perspectives for potential treatments aimed at the initial stage of higher-order α-synuclein aggregation. The single-molecule approach developed here can be broadly applied to the study of disease-related intrinsically disordered proteins.","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 1","pages":"016114"},"PeriodicalIF":6.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10908564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140022890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multifunctional scaffolds for biomedical applications: Crafting versatile solutions with polycaprolactone enriched by graphene oxide. 生物医学应用的多功能支架：用富含氧化石墨烯的聚己内酯制作多功能解决方案。

IF 6 3区医学

APL Bioengineering Pub Date : 2024-03-01 DOI: 10.1063/5.0184933

G Friggeri, I Moretti, F Amato, A G Marrani, F Sciandra, S G Colombarolli, A Vitali, S Viscuso, A Augello, L Cui, G Perini, M De Spirito, M Papi, V Palmieri

{"title":"Multifunctional scaffolds for biomedical applications: Crafting versatile solutions with polycaprolactone enriched by graphene oxide.","authors":"G Friggeri, I Moretti, F Amato, A G Marrani, F Sciandra, S G Colombarolli, A Vitali, S Viscuso, A Augello, L Cui, G Perini, M De Spirito, M Papi, V Palmieri","doi":"10.1063/5.0184933","DOIUrl":"10.1063/5.0184933","url":null,"abstract":"The pressing need for multifunctional materials in medical settings encompasses a wide array of scenarios, necessitating specific tissue functionalities. A critical challenge is the occurrence of biofouling, particularly by contamination in surgical environments, a common cause of scaffolds impairment. Beyond the imperative to avoid infections, it is also essential to integrate scaffolds with living cells to allow for tissue regeneration, mediated by cell attachment. Here, we focus on the development of a versatile material for medical applications, driven by the diverse time-definite events after scaffold implantation. We investigate the potential of incorporating graphene oxide (GO) into polycaprolactone (PCL) and create a composite for 3D printing a scaffold with time-controlled antibacterial and anti-adhesive growth properties. Indeed, the as-produced PCL-GO scaffold displays a local hydrophobic effect, which is translated into a limitation of biological entities-attachment, including a diminished adhesion of bacteriophages and a reduction of E. coli and S. aureus adhesion of ∼81% and ∼69%, respectively. Moreover, the ability to 3D print PCL-GO scaffolds with different heights enables control over cell distribution and attachment, a feature that can be also exploited for cellular confinement, i.e., for microfluidics or wound healing applications. With time, the surface wettability increases, and the scaffold can be populated by cells. Finally, the presence of GO allows for the use of infrared light for the sterilization of scaffolds and the disruption of any bacteria cell that might adhere to the more hydrophilic surface. Overall, our results showcase the potential of PCL-GO as a versatile material for medical applications.","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 1","pages":"016115"},"PeriodicalIF":6.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10908559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140022892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Layer-by-layer assembly of nanotheranostic particles for simultaneous delivery of docetaxel and doxorubicin to target osteosarcoma. 逐层组装纳米otheranostic颗粒，同时向骨肉瘤靶点输送多西他赛和多柔比星。

IF 6 3区医学

APL Bioengineering Pub Date : 2024-02-29 eCollection Date: 2024-03-01 DOI: 10.1063/5.0180831

Liam Desmond, Simone Margini, Emilio Barchiesi, Giuseppe Pontrelli, Anh N Phan, Piergiorgio Gentile

{"title":"Layer-by-layer assembly of nanotheranostic particles for simultaneous delivery of docetaxel and doxorubicin to target osteosarcoma.","authors":"Liam Desmond, Simone Margini, Emilio Barchiesi, Giuseppe Pontrelli, Anh N Phan, Piergiorgio Gentile","doi":"10.1063/5.0180831","DOIUrl":"10.1063/5.0180831","url":null,"abstract":"Osteosarcoma (OS) is a rare form of primary bone cancer, impacting approximately 3.4 × 106 individuals worldwide each year, primarily afflicting children. Given the limitations of existing cancer therapies, the emergence of nanotheranostic platforms has generated considerable research interest in recent decades. These platforms seamlessly integrate therapeutic potential of drug compounds with the diagnostic capabilities of imaging probes within a single construct. This innovation has opened avenues for enhanced drug delivery to targeted sites while concurrently enabling real-time monitoring of the vehicle's trajectory. In this study, we developed a nanotheranostic system employing the layer-by-layer (LbL) technique on a core containing doxorubicin (DOXO) and in-house synthesized carbon quantum dots. By utilizing chitosan and chondroitin sulfate as polyelectrolytes, we constructed a multilayered coating to encapsulate DOXO and docetaxel, achieving a coordinated co-delivery of both drugs. The LbL-functionalized nanoparticles exhibited an approximate size of 150 nm, manifesting a predominantly uniform and spherical morphology, with an encapsulation efficiency of 48% for both drugs. The presence of seven layers in these systems facilitated controlled drug release over time, as evidenced by in vitro release tests. Finally, the impact of the LbL-functionalized nanoparticles was evaluated on U2OS and Saos-2 osteosarcoma cells. The synergistic effect of the two drugs was found to be crucial in inducing cell death, particularly in Saos-2 cells treated with nanoparticles at concentrations higher than 10 μg/ml. Transmission electron microscopy analysis confirmed the internalization of the nanoparticles into both cell types through endocytic mechanisms, revealing an underlying mechanism of necrosis-induced cell death.","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 1","pages":"016113"},"PeriodicalIF":6.0,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10913103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140040640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Revolutionizing biomedical research: The imperative need for heart-kidney-connected organoids. 彻底改变生物医学研究：心肾相连有机体的迫切需要

IF 6 3区医学

APL Bioengineering Pub Date : 2024-02-27 eCollection Date: 2024-03-01 DOI: 10.1063/5.0190840

Sun-Sook Song, Hun-Jun Park, Yong Kyun Kim, Sun-Woong Kang

引用次数: 0

3D convolutional neural networks predict cellular metabolic pathway use from fluorescence lifetime decay data. 三维卷积神经网络从荧光寿命衰减数据预测细胞代谢途径的使用。

IF 6 3区医学

APL Bioengineering Pub Date : 2024-02-27 eCollection Date: 2024-03-01 DOI: 10.1063/5.0188476

Linghao Hu, Daniela De Hoyos, Yuanjiu Lei, A Phillip West, Alex J Walsh

{"title":"3D convolutional neural networks predict cellular metabolic pathway use from fluorescence lifetime decay data.","authors":"Linghao Hu, Daniela De Hoyos, Yuanjiu Lei, A Phillip West, Alex J Walsh","doi":"10.1063/5.0188476","DOIUrl":"10.1063/5.0188476","url":null,"abstract":"Fluorescence lifetime imaging of the co-enzyme reduced nicotinamide adenine dinucleotide (NADH) offers a label-free approach for detecting cellular metabolic perturbations. However, the relationships between variations in NADH lifetime and metabolic pathway changes are complex, preventing robust interpretation of NADH lifetime data relative to metabolic phenotypes. Here, a three-dimensional convolutional neural network (3D CNN) trained at the cell level with 3D NAD(P)H lifetime decay images (two spatial dimensions and one time dimension) was developed to identify metabolic pathway usage by cancer cells. NADH fluorescence lifetime images of MCF7 breast cancer cells with three isolated metabolic pathways, glycolysis, oxidative phosphorylation, and glutaminolysis were obtained by a multiphoton fluorescence lifetime microscope and then segmented into individual cells as the input data for the classification models. The 3D CNN models achieved over 90% accuracy in identifying cancer cells reliant on glycolysis, oxidative phosphorylation, or glutaminolysis. Furthermore, the model trained with human breast cancer cell data successfully predicted the differences in metabolic phenotypes of macrophages from control and POLG-mutated mice. These results suggest that the integration of autofluorescence lifetime imaging with 3D CNNs enables intracellular spatial patterns of NADH intensity and temporal dynamics of the lifetime decay to discriminate multiple metabolic phenotypes. Furthermore, the use of 3D CNNs to identify metabolic phenotypes from NADH fluorescence lifetime decay images eliminates the need for time- and expertise-demanding exponential decay fitting procedures. In summary, metabolic-prediction CNNs will enable live-cell and in vivo metabolic measurements with single-cell resolution, filling a current gap in metabolic measurement technologies.","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 1","pages":"016112"},"PeriodicalIF":6.0,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10901549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139991414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A multi-scale numerical approach to study monoclonal antibodies in solution. 研究溶液中单克隆抗体的多尺度数值方法。

IF 6.6 3区医学

APL Bioengineering Pub Date : 2024-02-26 eCollection Date: 2024-03-01 DOI: 10.1063/5.0186642

Marco Polimeni, Emanuela Zaccarelli, Alessandro Gulotta, Mikael Lund, Anna Stradner, Peter Schurtenberger

{"title":"A multi-scale numerical approach to study monoclonal antibodies in solution.","authors":"Marco Polimeni, Emanuela Zaccarelli, Alessandro Gulotta, Mikael Lund, Anna Stradner, Peter Schurtenberger","doi":"10.1063/5.0186642","DOIUrl":"10.1063/5.0186642","url":null,"abstract":"Developing efficient and robust computational models is essential to improve our understanding of protein solution behavior. This becomes particularly important to tackle the high-concentration regime. In this context, the main challenge is to put forward coarse-grained descriptions able to reduce the level of detail, while retaining key features and relevant information. In this work, we develop an efficient strategy that can be used to investigate and gain insight into monoclonal antibody solutions under different conditions. We use a multi-scale numerical approach, which connects information obtained at all-atom and amino-acid levels to bead models. The latter has the advantage of reproducing the properties of interest while being computationally much faster. Indeed, these models allow us to perform many-protein simulations with a large number of molecules. We can, thus, explore conditions not easily accessible with more detailed descriptions, perform effective comparisons with experimental data up to very high protein concentrations, and efficiently investigate protein-protein interactions and their role in phase behavior and protein self-assembly. Here, a particular emphasis is given to the effects of charges at different ionic strengths.","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 1","pages":"016111"},"PeriodicalIF":6.6,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10902793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139997824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fluid shear stress induced-endothelial phenotypic transition contributes to cerebral ischemia-reperfusion injury and repair. 流体剪切应力诱导的内皮表型转变有助于脑缺血再灌注损伤和修复。

IF 6 3区医学

APL Bioengineering Pub Date : 2024-02-26 eCollection Date: 2024-03-01 DOI: 10.1063/5.0174825

Denglian Sun, Jia Ma, Lingyu Du, Qiao Liu, Hongyan Yue, Chengxiu Peng, Hanxiao Chen, Guixue Wang, Xiaoheng Liu, Yang Shen

{"title":"Fluid shear stress induced-endothelial phenotypic transition contributes to cerebral ischemia-reperfusion injury and repair.","authors":"Denglian Sun, Jia Ma, Lingyu Du, Qiao Liu, Hongyan Yue, Chengxiu Peng, Hanxiao Chen, Guixue Wang, Xiaoheng Liu, Yang Shen","doi":"10.1063/5.0174825","DOIUrl":"10.1063/5.0174825","url":null,"abstract":"Long-term ischemia leads to insufficient cerebral microvascular perfusion and dysfunction. Reperfusion restores physiological fluid shear stress (FSS) but leads to serious injury. The mechanism underlying FSS-induced endothelial injury in ischemia-reperfusion injury (IRI) remains poorly understood. In this study, a rat model of middle cerebral artery occlusion was constructed to explore cerebrovascular endothelial function and inflammation in vivo. Additionally, the rat brain microvascular endothelial cells (rBMECs) were exposed to a laminar FSS of 0.5 dyn/cm2 for 6 h and subsequently restored to physiological fluid shear stress level (2 dyn/cm2) for 2 and 12 h, respectively. We found that reperfusion induced endothelial-to-mesenchymal transition (EndMT) in endothelial cells, leading to serious blood-brain barrier dysfunction and endothelial inflammation, accompanied by the nuclear accumulation of Yes-associated protein (YAP). During the later stage of reperfusion, cerebral endothelium was restored to the endothelial phenotype with a distinct change in mesenchymal-to-endothelial transition (MEndT), while YAP was translocated and phosphorylated in the cytoplasm. Knockdown of YAP or inhibition of actin polymerization markedly impaired the EndMT in rBMECs. These findings suggest that ischemia-reperfusion increased intensity of FSS triggered an EndMT process and, thus, led to endothelial inflammation and tissue injury, whereas continuous FSS induced a time-dependent reversal MEndT event contributing to the endothelial repair. This study provides valuable insight for therapeutic strategies targeting IRI.","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 1","pages":"016110"},"PeriodicalIF":6.0,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10898918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139984165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Improvement of clinical wound microcirculation diagnosis using an object tracking-based laser speckle contrast imaging system. 利用基于物体跟踪的激光斑点对比成像系统改进临床伤口微循环诊断。

IF 6.6 3区医学

APL Bioengineering Pub Date : 2024-01-29 eCollection Date: 2024-03-01 DOI: 10.1063/5.0172443

Meng-Che Hsieh, Chia-Yu Chang, Ching-Han Hsu, Yan-Ren Lin, Pei-You Hsieh, Congo Tak-Shing Ching, Lun-De Liao

{"title":"Improvement of clinical wound microcirculation diagnosis using an object tracking-based laser speckle contrast imaging system.","authors":"Meng-Che Hsieh, Chia-Yu Chang, Ching-Han Hsu, Yan-Ren Lin, Pei-You Hsieh, Congo Tak-Shing Ching, Lun-De Liao","doi":"10.1063/5.0172443","DOIUrl":"10.1063/5.0172443","url":null,"abstract":"Wound monitoring is crucial for effective healing, as nonhealing wounds can lead to tissue ulceration and necrosis. Evaluating wound recovery involves observing changes in angiogenesis. Laser speckle contrast imaging (LSCI) is vital for wound assessment due to its rapid imaging, high resolution, wide coverage, and noncontact properties. When using LSCI equipment, regions of interest (ROIs) must be delineated in lesion areas in images for quantitative analysis. However, patients with serious wounds cannot maintain constant postures because the affected areas are often associated with discomfort and pain. This leads to deviations between the drawn ROI and actual wound position when using LSCI for wound assessment, affecting the reliability of relevant assessments. To address these issues, we used the channel and spatial reliability tracker object tracking algorithm to develop an automatic ROI tracking function for LSCI systems. This algorithm is used to track and correct artificial movements in blood flow images, address the ROI position offset caused by the movement of the affected body part, increase the blood flow analysis accuracy, and improve the clinical applicability of LSCI systems. ROI tracking experiments were performed by simulating wounds, and the results showed that the intraclass correlation coefficient (ICC) ranged from 0.134 to 0.976. Furthermore, the object within the ROI affected tracking performance. Clinical assessments across wound types showed ICCs ranging from 0.798 to 0.917 for acute wounds and 0.628-0.849 for chronic wounds. We also discuss factors affecting tracking performance and propose strategies to enhance implementation effectiveness.","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 1","pages":"016105"},"PeriodicalIF":6.6,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10827336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139643061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dual delivery gene-activated scaffold directs fibroblast activity and keratinocyte epithelization. 双传递基因激活支架可引导成纤维细胞活性和角质细胞上皮化。

IF 6.6 3区医学

APL Bioengineering Pub Date : 2024-01-26 eCollection Date: 2024-03-01 DOI: 10.1063/5.0174122

Ashang L Laiva, Fergal J O'Brien, Michael B Keogh

{"title":"Dual delivery gene-activated scaffold directs fibroblast activity and keratinocyte epithelization.","authors":"Ashang L Laiva, Fergal J O'Brien, Michael B Keogh","doi":"10.1063/5.0174122","DOIUrl":"10.1063/5.0174122","url":null,"abstract":"Fibroblasts are the most abundant cell type in dermal skin and keratinocytes are the most abundant cell type in the epidermis; both play a crucial role in wound remodeling and maturation. We aim to assess the functionality of a novel dual gene activated scaffold (GAS) on human adult dermal fibroblasts (hDFs) and see how the secretome produced could affect human dermal microvascular endothelial cells (HDMVECs) and human epidermal keratinocyte (hEKs) growth and epithelization. Our GAS is a collagen chondroitin sulfate scaffold loaded with pro-angiogenic stromal derived factor (SDF-1α) and/or an anti-aging β-Klotho plasmids. hDFs were grown on GAS for two weeks and compared to gene-free scaffolds. GAS produced a significantly better healing outcome in the fibroblasts than in the gene-free scaffold group. Among the GAS groups, the dual GAS induced the most potent pro-regenerative maturation in fibroblasts with a downregulation in proliferation (twofold, p < 0.05), fibrotic remodeling regulators TGF-β1 (1.43-fold, p < 0.01) and CTGF (1.4-fold, p < 0.05), fibrotic cellular protein α-SMA (twofold, p < 0.05), and fibronectin matrix deposition (twofold, p < 0.05). The dual GAS secretome also showed enhancements of paracrine keratinocyte pro-epithelializing ability (1.3-fold, p < 0.05); basement membrane regeneration through laminin (6.4-fold, p < 0.005) and collagen IV (8.7-fold, p < 0.005) deposition. Our findings demonstrate enhanced responses in dual GAS containing hDFs by proangiogenic SDF-1α and β-Klotho anti-fibrotic rejuvenating activities. This was demonstrated by activating hDFs on dual GAS to become anti-fibrotic in nature while eliciting wound repair basement membrane proteins; enhancing a proangiogenic HDMVECs paracrine signaling and greater epithelisation of hEKs.","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 1","pages":"016104"},"PeriodicalIF":6.6,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10821797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139571885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0