Advances in stem cell biology and genetics with bioengineering science continuously lead breakthroughs and innovations in biotechnology. We harmonize fundamental sciences such as chemistry, biology, and physics with principles of engineering to generate innovative and effective therapeutic approaches, tissue mimicries and medical microdevices for medicine and pharmaceutical sciences. Our group focuses on bioengineering of novel native-like 3D cellular microenvironments, organ-on-a-chip platforms, and cell therapy approaches and integrates them for human health.
Biological organizations are highly hierarchical in architecture from the molecular to the macroscopic level. Such complexity in tissues is formed by building units that regulate and provide the system function. To mimic and bioengineer functional tissues, we need biomanufacturing tools that can generate and manipulate multi-scale building blocks. Bottom-up tissue engineering approaches focus on creating tissues by assembling heterogeneous building units such as biomacromolecules, cells, and cell-loaded microscale hydrogels in a multiscale manner. In our recent works, we demonstrated different cell and tissue assembly approaches utilizing acoustic, magnetic, micro robotic and bioprinting technologies to generate model platforms and tissues. Bioengineering approaches are essential for current therapeutic and diagnostic applications in medicine. Together with advances in genetics and cell biology, bioengineering tools provide key elements for novel and innovative medical technologies for human health.
Engineering platforms and systems for biofabrication of 3D tissues and microenvironments.
Representative bioengineered tissue constructs A. Engineering of large osteogenic grafts with rapid engraftment capacity using mesenchymal and endothelial progenitors from human adipose tissue (Guven et al. 2011), B. In vitro endothelial capillaries from stromal vascular fraction (Guven et al. 2011), C. Enhanced engraftment and functionality of bio-engineeredautologous dermo-epidermal skin grafts pre-vascularized with adipose-derived cells (Klar et al. 2014), D. Direct neural differentiation of mouse embryonic stem cells in 3D microenvironments, E. Biotunable acoustic node assembly of hepatic organoids (Chen et al. 2015), F. Guided and magnetic self-assembly of tunable magnetoceptive cardiac microtissues (Tasoglu et al. 2014).
Zhu Y, Serpooshan V, Wu S, Demirci U, Chen P, Güven S. Tissue Engineering of 3D Organotypic Microtissues by Acoustic Assembly. Methods Mol Biol. 2017 September: 1-12. doi:10.1073/pnas.1708621114.
Namkoong B, Güven S, Ramesan S, Liaudanskaya V, Abzhanov A, Demirci U. Recapitulating cranial osteogenesis with neural crest cells in 3-D microenvironments. Acta biomaterialia. 2016 February; 31: 301-311. doi:10.1016/j.actbio.2015.12.004.
Calibasi Kocal G, Güven S, Foygel K, Goldman A, Chen P, Sengupta S, Paulmurugan R, Baskin Y, Demirci U. Dynamic Microenvironment Induces Phenotypic Plasticity of Esophageal Cancer Cells Under Flow. Scientific reports. 2016 December; 6: 38221. doi:10.1038/srep38221.
Bouyer C, Chen P, Güven S, Demirtaş TT, Nieland TJ, Padilla F, Demirci U. A Bio-Acoustic Levitational (BAL) Assembly Method for Engineering of Multilayered, 3D Brain-Like Constructs, Using Human Embryonic Stem Cell Derived Neuro-Progenitors. Advanced materials (Deerfield Beach, Fla.). 2016 January; 28 (1): 161-7. doi:10.1002/adma.201503916.
Arslan-Yildiz A, El Assal R, Chen P, Guven S, Inci F, Demirci U. Towards artificial tissue models: past, present, and future of 3D bioprinting. Biofabrication. 2016 March; 8 (1): 014103. doi:10.1088/1758-5090/8/1/014103.
Saxer F, Scherberich A, Todorov A, Studer P, Miot S, Schreiner S, Güven S, Tchang LA, Haug M, Heberer M, Schaefer DJ, Rikli D, Martin I, Jakob M. Implantation of Stromal Vascular Fraction Progenitors at Bone Fracture Sites: From a Rat Model to a First-in-Man Study. Stem cells (Dayton, Ohio). 2016 December; 34 (12): 2956-2966. doi:10.1002/stem.2478.
Guven S, Lindsey JS, Poudel I, Chinthala S, Nickerson MD, Gerami-Naini B, Gurkan UA, Anchan RM, Demirci U. Functional maintenance of differentiated embryoid bodies in microfluidic systems: a platform for personalized medicine. Stem cells translational medicine. 2015 March; 4 (3): 261-8. doi:10.5966/sctm.2014-0119.
Durmus NG, Tekin HC, Guven S, Sridhar K, Arslan Yildiz A, Calibasi G, Ghiran I, Davis RW, Steinmetz LM, Demirci U. Magnetic levitation of single cells. Proceedings of the National Academy of Sciences of the United States of America. 2015 July; 112 (28): E3661-8. doi:10.1073/pnas.1509250112.
Guven S, Chen P, Inci F, Tasoglu S, Erkmen B, Demirci U. Multiscale assembly for tissue engineering and regenerative medicine. Trends in biotechnology. 2015 May; 33 (5): 269-279. doi:10.1016/j.tibtech.2015.02.003.
Luo Z, Guven S, Gozen I, Chen P, Tasoglu S, Anchan RM, Bai B, Demirci U. Deformation of a single mouse oocyte in a constricted microfluidic channel. Microfluidics and nanofluidics. 2015 October; 19 (4): 883-890. doi:10.1007/s10404-015-1614-0.
Tasoglu S, Yu CH, Liaudanskaya V, Guven S, Migliaresi C, Demirci U. Magnetic Levitational Assembly for Living Material Fabrication. Advanced healthcare materials. 2015 July; 4 (10): 1469-76, 1422. doi:10.1002/adhm.201500092.
Chen P, Güven S, Usta OB, Yarmush ML, Demirci U. Biotunable acoustic node assembly of organoids. Advanced healthcare materials. 2015 September; 4 (13): 1937-43. doi:10.1002/adhm.201500279.
Kaempfen A, Todorov A, Güven S, Largo RD, Jaquiéry C, Scherberich A, Martin I, Schaefer DJ. Engraftment of Prevascularized, Tissue Engineered Constructs in a Novel Rabbit Segmental Bone Defect Model. International journal of molecular sciences. 2015 June; 16 (6): 12616-30. doi:10.3390/ijms160612616.
Tasoglu S, Diller E, Guven S, Sitti M, Demirci U. Untethered micro-robotic coding of three-dimensional material composition. Nature communications. 2014 January; 5: 3124. doi:10.1038/ncomms4124.
Tasoglu S, Yu CH, Gungordu HI, Guven S, Vural T, Demirci U. Guided and magnetic self-assembly of tunable magnetoceptive gels. Nature communications. 2014 September; 5: 4702. doi:10.1038/ncomms5702.
Chen P, Luo Z, Güven S, Tasoglu S, Ganesan AV, Weng A, Demirci U. Microscale assembly directed by liquid-based template. Advanced materials (Deerfield Beach, Fla.). 2014 September; 26 (34): 5936-41. doi:10.1002/adma.201402079.
Klar AS, Güven S, Biedermann T, Luginbühl J, Böttcher-Haberzeth S, Meuli-Simmen C, Meuli M, Martin I, Scherberich A, Reichmann E. Tissue-engineered dermo-epidermal skin grafts prevascularized with adipose-derived cells. Biomaterials. 2014 June; 35 (19): 5065-78. doi:10.1016/j.biomaterials.2014.02.049.
Tasoglu S, Kavaz D, Gurkan UA, Guven S, Chen P, Zheng R, Demirci U. Paramagnetic levitational assembly of hydrogels. Advanced materials (Deerfield Beach, Fla.). 2013 February; 25 (8): 1137-43, 1081. doi:10.1002/adma.201200285.
Helmrich U, Di Maggio N, Güven S, Groppa E, Melly L, Largo RD, Heberer M, Martin I, Scherberich A, Banfi A. Osteogenic graft vascularization and bone resorption by VEGF-expressing human mesenchymal progenitors. Biomaterials. 2013 July; 34 (21): 5025-35. doi:10.1016/j.biomaterials.2013.03.040.
Güven S, Karagianni M, Schwalbe M, Schreiner S, Farhadi J, Bula S, Bieback K, Martin I, Scherberich A. Validation of an automated procedure to isolate human adipose tissue-derived cells by using the Sepax® technology. Tissue engineering. Part C, Methods. 2012 August; 18 (8): 575-82. doi:10.1089/ten.TEC.2011.0617.
Mehrkens A, Saxer F, Güven S, Hoffmann W, Müller AM, Jakob M, Weber FE, Martin I, Scherberich A. Intraoperative engineering of osteogenic grafts combining freshly harvested, human adipose-derived cells and physiological doses of bone morphogenetic protein-2. European cells & materials. 2012 September; 24: 308-19.
Güven S, Mehrkens A, Saxer F, Schaefer DJ, Martinetti R, Martin I, Scherberich A. Engineering of large osteogenic grafts with rapid engraftment capacity using mesenchymal and endothelial progenitors from human adipose tissue. Biomaterials. 2011 September; 32 (25): 5801-9. doi:10.1016/j.biomaterials.2011.04.064.
Papadimitropoulos A, Scherberich A, Güven S, Theilgaard N, Crooijmans HJ, Santini F, Scheffler K, Zallone A, Martin I. A 3D in vitro bone organ model using human progenitor cells. European cells & materials. 2011 May; 21: 445-58; discussion 458.
Müller AM, Mehrkens A, Schäfer DJ, Jaquiery C, Güven S, Lehmicke M, Martinetti R, Farhadi I, Jakob M, Scherberich A, Martin I. Towards an intraoperative engineering of osteogenic and vasculogenic grafts from the stromal vascular fraction of human adipose tissue. European cells & materials. 2010 March; 19: 127-35.