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    The apoptotic effect of ozone therapy on mitochondria of highly metastatic breast cancer cell line MDA-MB-231 using in vitro approaches
    (KeAi, 2022) Inac, Elif; Unsal, Naz; Yilmaz, Hazal; Erkisi, Selena; Yildirim, Merve; Tanriver, Yildiray; Koçak, Polen
    Ozone (O3) gas is the triatomic state of oxygen and it is used as a disinfection agent due to its strong oxidizing effect, since its discovery in the mid-nineteenth century. Ozone therapy is also an alternative therapeutic approach for some diseases like circulatory disorders, AIDS, asthma, cardiovascular diseases, and certain types of cancer by increasing the oxygen levels in the blood by external addition of ozone to the body. In this study, the therapeutic potential of ozone therapy was examined by inhibiting the growth of breast cancer cells in a dose-dependent procedure. Ozone concentrations varying from 5 to 20 ?g/ml were applied to the MDA-MB-231, human breast adenocarcinoma and HUVEC, human umbilical vein endothelium, cell lines, and MDA cells demonstrated an increased rate of death while its migration potential decreases. RT-PCR analysis showed mRNA expression levels of pro-apoptotic genes demonstrated higher folds in MDA cells after 10 ?g/ml treatment. In the same context, Annexin V/PI and cell cycle analysis also concluded that ozone therapy causes apoptotic cell death on breast tumor cells. The use of ozone therapy for cancer treatment requires further and extensive research. However, this research has shown that ozone therapy is a promising source for cancer treatment in a way by inhibiting the proliferation of breast tumor cells
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    Hybrid extracellular vesicles-liposome incorporated advanced bioink to deliver microRNA
    (IOP Publishing, 2022) Elkhoury, Kamil; Chen, Mo; Koçak, Polen; Enciso-Martínez, Eduardo; Bassous, Nicole Joy; Chul Lee, Myung; Byambaa, Batzaya; Rezaei, Zahra; Li, Yang; Ubina López , María Elizabeth; Gurian, Melvin; Sobahi, Nebras; Asif Hussain, Mohammad; Sanchez-Gonzalez, Laura; Leijten, Jeroen; Hassan, Shabir; Arab-Tehrany, Elmira; Ellis Ward, Jennifer; Shin, Su Ryon
    In additive manufacturing, bioink formulations govern strategies to engineer 3D living tissues that mimic the complex architectures and functions of native tissues for successful tissue regeneration. Conventional 3D-printed tissues are limited in their ability to alter the fate of laden cells. Specifically, the efficient delivery of gene expression regulators (i.e. microRNAs (miRNAs)) to cells in bioprinted tissues has remained largely elusive. In this study, we explored the inclusion of extracellular vesicles (EVs), naturally occurring nanovesicles (NVs), into bioinks to resolve this challenge. EVs show excellent biocompatibility, rapid endocytosis, and low immunogenicity, which lead to the efficient delivery of miRNAs without measurable cytotoxicity. EVs were fused with liposomes to prolong and control their release by altering their physical interaction with the bioink. Hybrid EVs-liposome (hEL) NVs were embedded in gelatin-based hydrogels to create bioinks that could efficiently encapsulate and deliver miRNAs at the target site in a controlled and sustained manner. The regulation of cells' gene expression in a 3D bioprinted matrix was achieved using the hELs-laden bioink as a precursor for excellent shape fidelity and high cell viability constructs. Novel regulatory factors-loaded bioinks will expedite the translation of new bioprinting applications in the tissue engineering field.
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    Hybrid stromal vascular fraction (hybrid-SVF): a new paradigm in mechanical regenerative cell processing
    (Lippincott Williams & Wilkins, 2022) Tiryaki, Tunc; Cohen, Steven Roy; Türkay, Serli Canikyan; Koçak, Polen; Sterodimas, Aris; Schlaudraff, Kai-Uwe; Demir, Isil Akguen; Agovino, Annarita; Kul, Yaren
    Background:Enzymatic digestion of extracellular matrix (ECM) from lipoaspirate is the conventional form of harvesting stromal vascular fraction (SVF) called enzymatically digested SVF (E-SVF). Mechanical SVF (M-SVF) isolation has emerged as an alternative method, but it has also some limitations in terms of lower cell viability and diminished cell counts. To enhance the SVF qualitatively and quantitatively, we propose a novel concept called hybrid-SVF, in which we combine M-SVF with the concentrated parts of adipose tissue after centrifugation, which is called stromal vascular matrix (SVM). Methods:Hybrid-SVF injection was applied as an adjunctive therapy to fat grafting in 88 patients and 11 samples were evaluated in the laboratory for cell count, viability and cell activity. Results:Experimental results determined that SVM part showed higher cellular activity. SVM and M-SVF showed higher cellular potency than E-SVF. Clinically, none of the patients required an additional session for fat grafting since there was no significant graft resorption. However, seven patients asked for further volume augmentation due to their individual preferences. No major complication was encountered. Conclusions:The usage of hybrid-SVF has a very high regenerative potential due to the ECM support and exceptionally high cell yield in addition to preserved cell potency. Although there are ongoing studies focusing on optimizing cell counts and further clinical applications, we believe that our preliminary results might create a paradigm shift in the area of regenerative fat grafting.
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    Selection of natural biomaterials for micro-tissue and organ-on-chip models
    (2022) Bal Öztürk, Ayça; Cecen, Berivan; Yaşayan, Gökçen; Alarçin, Emine; Koçak, Polen; Tutar, Rümeysa; Kozacı, Leyla Didem; Ryon Shin, Su; K Miri, Amir
    The desired organ in micro-tissue models of organ-on-a-chip (OoC) devices dictates the optimum biomaterials, divided into natural and synthetic biomaterials. They can resemble biological tissues' biological functions and architectures by constructing bioactivity of macromolecules, cells, nanoparticles, and other biological agents. The inclusion of such components in OoCs allows them having biological processes, such as basic biorecognition, enzymatic cleavage, and regulated drug release. In this report, we review natural-based biomaterials that are used in OoCs and their main characteristics. We address the preparation, modification, and characterization methods of natural-based biomaterials and summarize recent reports on their applications in the design and fabrication of micro-tissue models. This article will help bioengineers select the proper biomaterials based on developing new techn