{"title":"Toward Blood-Based Precision Medicine: Identifying Age-Sex-Specific Vascular Biomarker Quantities on Circulating Vascular Cells.","authors":"Yingye Fang, Ling Chen, P I Imoukhuede","doi":"10.1007/s12195-023-00771-1","DOIUrl":"10.1007/s12195-023-00771-1","url":null,"abstract":"<p><strong>Introduction: </strong>Abnormal angiogenesis is central to vascular disease and cancer, and noninvasive biomarkers of vascular origin are needed to evaluate patients and therapies. Vascular endothelial growth factor receptors (VEGFRs) are often dysregulated in these diseases, making them promising biomarkers, but the need for an invasive biopsy has limited biomarker research on VEGFRs. Here, we pioneer a blood biopsy approach to quantify VEGFR plasma membrane localization on two circulating vascular proxies: circulating endothelial cells (cECs) and circulating progenitor cells (cPCs).</p><p><strong>Methods: </strong>Using quantitative flow cytometry, we examined VEGFR expression on cECs and cPCs in four age-sex groups: peri/premenopausal females (aged < 50 years), menopausal/postmenopausal females (≥ 50 years), and younger and older males with the same age cut-off (50 years).</p><p><strong>Results: </strong>cECs in peri/premenopausal females consisted of two VEGFR populations: VEGFR-low (~ 55% of population: population medians ~ 3000 VEGFR1 and 3000 VEGFR2/cell) and VEGFR-high (~ 45%: 138,000 VEGFR1 and 39,000-236,000 VEGFR2/cell), while the menopausal/postmenopausal group only possessed the VEGFR-low cEC population; and 27% of cECs in males exhibited high plasma membrane VEGFR expression (206,000 VEGFR1 and 155,000 VEGFR2/cell). The absence of VEGFR-high cEC subpopulations in menopausal/postmenopausal females suggests that their high-VEGFR cECs are associated with menstruation and could be noninvasive proxies for studying the intersection of age-sex in angiogenesis. VEGFR1 plasma membrane localization in cPCs was detected only in menopausal/postmenopausal females, suggesting a menopause-specific regenerative mechanism.</p><p><strong>Conclusions: </strong>Overall, our quantitative, noninvasive approach targeting cECs and cPCs has provided the first insights into how sex and age influence VEGFR plasma membrane localization in vascular cells.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s12195-023-00771-1.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"16 3","pages":"189-204"},"PeriodicalIF":2.8,"publicationDate":"2023-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10338416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9828433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Bio-adhesive Macroporous Hydrogels for In Situ Recruitment and Modulation of Dendritic Cells.","authors":"Joonsu Han, Rimsha Bhatta, Hua Wang","doi":"10.1007/s12195-023-00770-2","DOIUrl":"10.1007/s12195-023-00770-2","url":null,"abstract":"<p><strong>Introduction: </strong>Biomaterials that enable in situ recruitment and modulation of immune cells have demonstrated tremendous promise for developing potent cancer immunotherapy such as therapeutic cancer vaccine. One challenge related to biomaterial scaffold-based cancer vaccines is the development of macroporous materials that are biocompatible and stable, enable controlled release of chemokines to actively recruit a large number of dendritic cells (DCs), contain macropores that are large enough to home the recruited DCs, and support the survival and proliferation of DCs.</p><p><strong>Methods: </strong>Bio-adhesive macroporous gelatin hydrogels were synthesized and characterized for mechanical properties, porous structure, and adhesion towards tissues. The recruitment of immune cells including DCs to chemokine-loaded bioadhesive macroporous gels was analyzed. The ability of gels loaded with granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor extracellular vesicles (EVs) to elicit tumor-specific CD8<sup>+</sup> T cell responses was also analyzed.</p><p><strong>Results: </strong>Here we develop a bioadhesive macroporous hydrogel that can strongly adhere to tissues, contain macropores that are large enough to home immune cells, are mechanically tough, and enable controlled release of chemokines to recruit and modulate immune cells in situ. The macroporous hydrogel is composed of a double crosslinked network of gelatin and polyacrylic acid, and the macropores are introduced via cryo-polymerization. By incorporating GM-CSF and tumor EVs into the macroporous hydrogel, a high number of DCs can be recruited in situ to process and present EV-encased antigens. These tumor antigen-presenting DCs can then traffic to lymphatic tissues to prime antigen-specific CD8<sup>+</sup> T cells.</p><p><strong>Conclusion: </strong>This bioadhesive macroporous hydrogel system provides a new platform for in situ recruitment and modulation of DCs and the development of enhanced immunotherapies including tumor EV vaccines. We also envision the promise of this material system for drug delivery, tissue regeneration, long-term immunosuppression, and many other applications.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s12195-023-00770-2.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"16 4","pages":"355-367"},"PeriodicalIF":2.3,"publicationDate":"2023-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10550891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41106583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matthew R Aronson, Amrita Mehta, Ryan M Friedman, Daniel D Ghaderi, Ryan C Borek, Hoang C B Nguyen, Kendra S McDaid, Ian N Jacobs, Natasha Mirza, Riccardo Gottardi
{"title":"Amelioration of Subglottic Stenosis by Antimicrobial Peptide Eluting Endotracheal Tubes.","authors":"Matthew R Aronson, Amrita Mehta, Ryan M Friedman, Daniel D Ghaderi, Ryan C Borek, Hoang C B Nguyen, Kendra S McDaid, Ian N Jacobs, Natasha Mirza, Riccardo Gottardi","doi":"10.1007/s12195-023-00769-9","DOIUrl":"10.1007/s12195-023-00769-9","url":null,"abstract":"<p><strong>Introduction: </strong>Pediatric subglottic stenosis (SGS) results from prolonged intubation where scar tissue leads to airway narrowing that requires invasive surgery. We have recently discovered that modulating the laryngotracheal microbiome can prevent SGS. Herein, we show how our patent-pending antimicrobial peptide-eluting endotracheal tube (AMP-ET) effectively modulates the local airway microbiota resulting in reduced inflammation and stenosis resolution.</p><p><strong>Materials and methods: </strong>We fabricated mouse-sized ETs coated with a polymeric AMP-eluting layer, quantified AMP release over 10 days, and validated bactericidal activity for both planktonic and biofilm-resident bacteria against <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i>. Ex vivo testing: we inserted AMP-ETs and ET controls into excised laryngotracheal complexes (LTCs) of C57BL/6 mice and assessed biofilm formation after 24 h. In vivo testing: AMP-ETs and ET controls were inserted in sham or SGS-induced LTCs, which were then implanted subcutaneously in receptor mice, and assessed for immune response and SGS severity after 7 days.</p><p><strong>Results: </strong>We achieved reproducible, linear AMP release at 1.16 µg/day resulting in strong bacterial inhibition in vitro and ex vivo. In vivo, SGS-induced LTCs exhibited a thickened scar tissue typical of stenosis, while the use of AMP-ETs abrogated stenosis. Notably, SGS airways exhibited high infiltration of T cells and macrophages, which was reversed with AMP-ET treatment. This suggests that by modulating the microbiome, AMP-ETs reduce macrophage activation and antigen specific T cell responses resolving stenosis progression.</p><p><strong>Conclusion: </strong>We developed an AMP-ET platform that reduces T cell and macrophage responses and reduces SGS in vivo via airway microbiome modulation.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s12195-023-00769-9.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"16 4","pages":"369-381"},"PeriodicalIF":2.3,"publicationDate":"2023-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10550884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41100408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tia C L Kohs, Samuel N Clarin, Rich G Carter, Karl Mundorff, Princess I Imoukhuede, Anand Ramamurthi, Gang Bao, Michael R King, Owen J T McCarty
{"title":"Correction: Innovation and Entrepreneurship in Promotion and Tenure in Biomedical Engineering.","authors":"Tia C L Kohs, Samuel N Clarin, Rich G Carter, Karl Mundorff, Princess I Imoukhuede, Anand Ramamurthi, Gang Bao, Michael R King, Owen J T McCarty","doi":"10.1007/s12195-023-00768-w","DOIUrl":"10.1007/s12195-023-00768-w","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1007/s12195-023-00767-x.].</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"16 3","pages":"187"},"PeriodicalIF":2.8,"publicationDate":"2023-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10338405/pdf/12195_2023_Article_768.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9828438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tia C L Kohs, Samuel N Clarin, Rich G Carter, Karl Mundorff, Princess I Imoukhuede, Anand Ramamurthi, Gang Bao, Michael R King, Owen J T McCarty
{"title":"Innovation and Entrepreneurship in Promotion and Tenure in Biomedical Engineering: Communication from the Biomedical Engineering Society Long Range Planning Committee.","authors":"Tia C L Kohs, Samuel N Clarin, Rich G Carter, Karl Mundorff, Princess I Imoukhuede, Anand Ramamurthi, Gang Bao, Michael R King, Owen J T McCarty","doi":"10.1007/s12195-023-00767-x","DOIUrl":"10.1007/s12195-023-00767-x","url":null,"abstract":"<p><p>Promotion and tenure (P&T) remain the central tenets of academia. The criteria for P&T both create and reflect the mission of an institution. The discipline of biomedical engineering is built upon the invention and translation of tools to address unmet clinical needs. 'Broadening the bar' for P&T to include efforts in innovation, entrepreneurship, and technology-based transfer (I/E/T) will require establishing the criteria and communication of methodology for their evaluation. We surveyed the department chairs across the fields of biomedical and bioengineering to understand the state-of-the-art in incorporation, evaluation, and definition of I/E/T as applied to the P&T process. The survey results reflected a commitment to increasing and respecting I/E/T activities as part of the P&T criteria. This was balanced by an equally strong desire for improving the education and policy for evaluating I/E/T internally as well as externally. The potential for 'broadening the bar' for P&T to include I/E/T activities in biomedical engineering may serve as an example for other fields in engineering and applied sciences, and a template for potential inclusion of additional efforts such as diversity, equity, and inclusion (DEI) into the pillars of scholarship, education, and service.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"16 3","pages":"181-185"},"PeriodicalIF":2.8,"publicationDate":"2023-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10338410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9828439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaoxiao Chen, Youjun Xia, Wenqiang Du, Han Liu, Ran Hou, Yiyu Song, Wenhu Xu, Yuxin Mao, Jianfeng Chen
{"title":"Contact Guidance Drives Upward Cellular Migration at the Mesoscopic Scale.","authors":"Xiaoxiao Chen, Youjun Xia, Wenqiang Du, Han Liu, Ran Hou, Yiyu Song, Wenhu Xu, Yuxin Mao, Jianfeng Chen","doi":"10.1007/s12195-023-00766-y","DOIUrl":"10.1007/s12195-023-00766-y","url":null,"abstract":"<p><strong>Introduction: </strong>Cancer metastasis is associated with increased cancer incidence, recurrence, and mortality. The role of cell contact guidance behaviors in cancer metastasis has been recognized but has not been elucidated yet.</p><p><strong>Methods: </strong>The contact guidance behavior of cancer cells in response to topographical constraints is identified using microgrooved substrates with varying dimensions at the mesoscopic scale. Then, the cell morphology is determined to quantitatively analyze the effects of substrate dimensions on cells contact guidance. Cell density and migrate velocity signatures within the cellular population are determined using time-lapse phase-contrast microscopy. The effect of soluble factors concentration is determined by culturing cells upside down. Then, the effect of cell-substrate interaction on cell migration is investigated using traction force microscopy.</p><p><strong>Results: </strong>With increasing depth and decreasing groove width, cell elongation and alignment are enhanced, while cell spreading is inhibited. Moreover, cells display preferential distribution on the ridges, which is found to be more pronounced with increasing depth and groove width. Determinations of cell density and migration velocity signatures reveal that the preferential distribution on ridges is caused by cell upward migration. Combined with traction force measurement, we find that migration toward ridges is governed by different cell-substrate interactions between grooves and ridges caused by geometrical constraints. Interestingly, the upward migration of cells at the mesoscopic scale is driven by entropic maximization.</p><p><strong>Conclusions: </strong>The mesoscopic cell contact guidance mechanism based on the entropic force driven theory provides basic support for the study of cell alignment and migration along healthy tissues with varying size, thereby aiding in the prediction of cancer metastasis.</p><p><strong>Graphical abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s12195-023-00766-y.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"16 3","pages":"205-218"},"PeriodicalIF":2.8,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10338420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9828436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Place for Large Language Models in Scientific Publishing, Apart from Credited Authorship.","authors":"Michael R King","doi":"10.1007/s12195-023-00765-z","DOIUrl":"10.1007/s12195-023-00765-z","url":null,"abstract":"","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"16 2","pages":"95-98"},"PeriodicalIF":2.8,"publicationDate":"2023-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10121920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9744141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Callie M Weber, Mikayla N Harris, Sophia M Zic, Gurneet S Sangha, Nicole S Arnold, Douglas F Dluzen, Alisa Morss Clyne
{"title":"Angiotensin II Increases Oxidative Stress and Inflammation in Female, But Not Male, Endothelial Cells.","authors":"Callie M Weber, Mikayla N Harris, Sophia M Zic, Gurneet S Sangha, Nicole S Arnold, Douglas F Dluzen, Alisa Morss Clyne","doi":"10.1007/s12195-023-00762-2","DOIUrl":"10.1007/s12195-023-00762-2","url":null,"abstract":"<p><strong>Introduction: </strong>Women are at elevated risk for certain cardiovascular diseases, including pulmonary arterial hypertension, Alzheimer's disease, and vascular complications of diabetes. Angiotensin II (AngII), a circulating stress hormone, is elevated in cardiovascular disease; however, our knowledge of sex differences in the vascular effects of AngII are limited. We therefore analyzed sex differences in human endothelial cell response to AngII treatment.</p><p><strong>Methods: </strong>Male and female endothelial cells were treated with AngII for 24 h and analyzed by RNA sequencing. We then used endothelial and mesenchymal markers, inflammation assays, and oxidative stress indicators to measure female and male endothelial cell functional changes in response to AngII.</p><p><strong>Results: </strong>Our data show that female and male endothelial cells are transcriptomically distinct. Female endothelial cells treated with AngII had widespread gene expression changes related to inflammatory and oxidative stress pathways, while male endothelial cells had few gene expression changes. While both female and male endothelial cells maintained their endothelial phenotype with AngII treatment, female endothelial cells showed increased release of the inflammatory cytokine interleukin-6 and increased white blood cell adhesion following AngII treatment concurrent with a second inflammatory cytokine. Additionally, female endothelial cells had elevated reactive oxygen species production compared to male endothelial cells after AngII treatment, which may be partially due to nicotinamide adenine dinucleotide phosphate oxidase-2 (NOX2) escape from X-chromosome inactivation.</p><p><strong>Conclusions: </strong>These data suggest that endothelial cells have sexually dimorphic responses to AngII, which could contribute to increased prevalence of some cardiovascular diseases in women.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s12195-023-00762-2.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"16 2","pages":"127-141"},"PeriodicalIF":2.8,"publicationDate":"2023-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10121986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9447375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Iván M López-Rodulfo, Elisa Villa-Martínez, Amelia Rios, Bruno Escalante
{"title":"Caveolin Delivered by Ultrasound-Mediated Microbubble Destruction Prevents Endothelial Cell Proliferation.","authors":"Iván M López-Rodulfo, Elisa Villa-Martínez, Amelia Rios, Bruno Escalante","doi":"10.1007/s12195-023-00763-1","DOIUrl":"10.1007/s12195-023-00763-1","url":null,"abstract":"<p><strong>Introduction: </strong>The nitric oxide synthase (eNOS) is an important regulator of vascular homeostasis. eNOS is modulated by intracellular mechanisms that include protein-protein interaction with Caveolin-1 (Cav). Cav binds to and impairs eNOS activation reducing vascular permeability and angiogenesis. Blocking of eNOS by Cav has been proposed as therapeutic antiangiogenic approach. However, the efficient and controlled delivery of the peptide requires to be solved.</p><p><strong>Methods: </strong>The effect of antennapedia (AP)-Cav loaded into microbubbles (MBs) and delivered by ultrasound-mediated microbubble destruction (UMMD) into brain endothelial cells (bEnd.3 cells) was evaluated on NO production using DAF2-DA, cell migration assessed by the wound healing assay, cell proliferation with BrdU, and ex-vivo angiogenesis in rat aortic rings.</p><p><strong>Results: </strong>An enhanced inhibitory effect of AP-Cav was observed on cells treated with UMMD. MBs and ultrasound disruption delivery of AP-Cav increased acetylcholine-induced NO release, wound healing, cell proliferation, and angiogenesis inhibition on bEnd.3 cells, compared to free AP-Cav administration.</p><p><strong>Conclusion: </strong>We demonstrated that the delivery of Cav via AP-Cav-loaded MBs and UMMD may be an administration method for Cav that would increase its therapeutic potential by enhancing efficacy and cellular specificity.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"16 3","pages":"219-229"},"PeriodicalIF":2.8,"publicationDate":"2023-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10338419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9823085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daniel C Sasson, Sara Islam, Kaiti Duan, Biraja C Dash, Henry C Hsia
{"title":"TNF-α Preconditioning Promotes a Proangiogenic Phenotype in hiPSC-Derived Vascular Smooth Muscle Cells.","authors":"Daniel C Sasson, Sara Islam, Kaiti Duan, Biraja C Dash, Henry C Hsia","doi":"10.1007/s12195-023-00764-0","DOIUrl":"10.1007/s12195-023-00764-0","url":null,"abstract":"<p><strong>Introduction: </strong>hiPSC-VSMCs have been suggested as therapeutic agents for wound healing and revascularization through the secretion of proangiogenic factors. However, methods of increasing cell paracrine secretion and survivability have thus far yielded inconsistent results. This study investigates the effect of pre-conditioning of hiPSC-VSMCs with TNF-α and their integration into 3D collagen scaffolds on cellular viability and secretome.</p><p><strong>Methods: </strong>hiPSC-VSMCs were dual-plated in a 2D environment. TNF-α was introduced to one plate. Following incubation, cells from each plate were divided and added to type-I collagen scaffolds. TNF-α was introduced to two sets of scaffolds, one from each 2D plate. Following incubation, scaffolds were harvested for their media, tested for cell survivability, cytotoxicity, and imaged. Intra-media VEGF and bFGF levels were evaluated using ELISA testing.</p><p><strong>Results: </strong>hiPSC-VSMCs exposed to TNF-α during collagen scaffold proliferation and preconditioning showed an increase in cell viability and less cytotoxicity compared to non-exposed cells and solely-preconditioned cells. Significant increases in bFGF expression were found in pre-conditioned cell groups with further increases found in cells subsequently exposed during intra-scaffold conditioning. A significant increase in VEGF expression was found in cell groups exposed during both pre-conditioning and intra-scaffold conditioning. Fibroblasts treated with any conditioned media demonstrated increased migration potential.</p><p><strong>Conclusions: </strong>Conditioning hiPSC-VSMCs embedded in scaffolds with TNF-α improves cellular viability and increases the secretion of paracrine factors necessary for wound healing mechanisms such as migration.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s12195-023-00764-0.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"16 3","pages":"231-240"},"PeriodicalIF":2.8,"publicationDate":"2023-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10338418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9828432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}