Therapeutic Bioengineering

Principal Investigator: Assoc. Prof. Sinan GÜVEN

Advances in stem cell biology and genetics, when combined with bioengineering approaches, continuously generate groundbreaking innovations in biotechnology. Our research particularly focuses on adapting stem cell and organoid technologies to clinical and pharmaceutical applications by addressing them through fundamental sciences and engineering principles. Our group develops pluripotent stem cell–based organoids and, with the aim of creating disease models, drug testing and repurposing platforms, designs 3D cell microenvironments and organ-on-chip systems. These organoid-based in vitro models, which will replace animal experiments, are strengthening our academic contributions to the healthcare industry of our country with each passing day.

Among our goals is to transfer our expertise and experience in diverse fields such as ophthalmology, orthopedics, neurology, and cardiology into new areas. Building on the expertise we have gained so far in pluripotent stem cell–based organoids and secretomes for eye health and biological development, we are carrying out pioneering projects that will be the first in the organoid literature by functionally establishing the eye-brain axis under in vitro conditions

Induced pluripotent stem cell-based organoids in ophthalmology and neuroscience generated in Güven Lab towards establishing in vitro eye-brain interaction platform

Engineering platforms and systems for biofabrication of 3D tissues and microenvironments.

Services & Research Areas

1. Stem Cell Differentiation

• Induced Pluripotent Stem Cell (iPSC) differentiation
  Corneal epithelium, corneal endothelium, retina, neural progenitors, parasympathetic neurons
• Embryonic stem cell differentiation (mouse)
  Lacrimal acinar and ductal cells
• Mesenchymal stem cell differentiation
  Bone marrow-derived mesenchymal stem cells
  Adipose tissue-derived mesenchymal stem cells

2. Organoid Development and Drug Testing/Screening

• Ocular system: Lacrimal gland, cornea, retina
• Neural structures: Cerebral brain, hypothalamus
• Tumoroids: Ocular surface squamous neoplasia tumoroids
• Rare disease model development

3. Design and Fabrication of Microfluidic Organ-on-Chip Systems

• PMMA-based
• PDMS-based
• Microfluidic chip integrated infrared Oxygen, Carbon dioxide, and pH sensors

4. 3D Dynamic and Static Cell-Tissue Culture

• Hydrogel-based systems (GelMA, PEGDA, fibrin, alginate)
• Spheroid culture (healthy and cancer cell lines)
• Cell carrier scaffold systems

5. Macrophage – Microglia Differentiation

• Under static and dynamic conditions
• Differentiation in 3D environments

6. Organoid-Based Extracellular Vesicle Isolation and Characterization

Publications

Yılmaz A, Özbilgiç R, Polatlı E, Erbay İH, Sağ D, Güven S, Macrophage Polarization Profiling in Dynamic Culture System. Cel. Mol. Bioeng. (2025). https://doi.org/10.1007/s12195-025-00863-0

Kahveci B, Polatli E, Evranos AE, Güner H, Bastanlar Y, Karakülah G, Güven S, BrAIn: A comprehensive artificial intelligence-based morphology analysis system for brain organoids and neuroscience, bioRxiv, doi: 10.1101/2025.02.19.638973

Koc AC, Sari V, Kocak G, Recber T, Nemutlu E, Aberdam D, Güven S, Patient-derived cornea organoid model to study metabolomic characterization of rare disease: aniridia-associated keratopathy, BMC Ophthalmol 25, 14 (2025). https://doi.org/10.1186/s12886-024-03831-w

Dabagh S, Javanifar R, Kaya M, Ebrahimi A, Güven S, Kaya BM, Esenturk O, Askin A, Güzel FD, Uysal O, Sarıboyacı AE, Ghorbanpoor H, Avci H, Electrosprayed MnFe2O4/PVDF membrane integrated microfluidic chip for amoxicillin removal with real-time monitoring of pH and dissolved oxygen, Journal of Environmental Chemical Engineering 12 (2024) 114895.

Kahveci B, Polatli E, Bastanlar Y, Guven S, OrganoLabeler: A Quick and Accurate Annotation Tool for Organoid Images, ACS Omega 2024, 9, 46, 46117–46128

Utine CA, Güven S, Tissue Engineering and Ophthalmology. Turk J Ophthalmol. 2024 Jun;54(3):159-169. doi: 10.4274/tjo.galenos.2024.49779.

Koçak G, Uyulgan S, Polatlı E, Sarı V, Kahveci B, Bursali A, Binokay L, Reçber T, Nemutlu E, Mardinoğlu A, Karakülah G, Utine CA, Güven S., Generation of Anterior Segment of the Eye Cells from hiPSCs in Microfluidic Platforms. Advanced Biology May;8(5): e2400018.          doi: 10.1002/adbi.202400018. 2024 

Engür D, Ercan İ, Kiser Ç, Tüfekçi KU, Soylu KS, Cilaker MS, Özhan HG, Güven S, Kumral A, Genç Ş, "Hydrogen peroxide signaling modulates neuronal differentiation via microglial polarization and Wnt/β-catenin pathway", European Review for Medical and Pharmacological Sciences, vol.27, 2023

Erbay İH, Polatlı E, Koç AC, Özbilgiç R, Karaman O, Güven S, Bioengineering bone‐on‐a‐chip model harnessing osteoblastic and osteoclastic resolution, Advanced Engineering Materials, 2023, 2201063. https://doi.org/10.1002/adem.202201063

Asal M, Kocak G, Sari V, Recber T, Nemutlu E, Utine CA, Guven S, Development of lacrimal gland organoids from human iPSC derived ocular cells, Frontiers in Cell and Developmental Biology 10, 2444, 2023

Kasal K, Güven S, Utine CA, Current methodology and cell sources for lacrimal gland tissue engineering, Experimental Eye Research, 2022, 109138

Projects

TÜBİTAK 1001 125Z345, 2025-2027, Development of Disease Modeling and Micro-Physiological Drug Testing Platform Using Induced Pluripotent Stem Cell-Based Corneal Organoids

TÜSEB-B Group 46435, 2025-2027, Development of Tear Drops Based on Organoid Secretome

TÜBİTAK 1001 124Z226, 2024-2026, Investigation of Retinohypothalamic Pathway Development Using Hypothalamus-Retina Assembloid Model and Profiling with Multi-Omics Approach

TÜBİTAK 1004 22AG008 MAESTRO, 2022–2026, Micro Medical Technologies Platform. Spheroid Culture and Drug Testing via Magnetic Levitation on a Microfluidic System (PI: Assoc. Prof. H. Cumhur Tekin, IZTECH)

DEU - ADEP TSA-2025-3725, 2025-2028, Development of an Organ-on-Chip Platform to Provide Neural Stimulation of Organoid-Based Lacrimal Gland for Dry Eye Syndrome

Horizon-MSCA-Cofund-2021, 2023-2027, BIOTIN Biomedical Technologies and Innovation Doctoral Programme (Coordinator: Prof. Dr. Volga Bulmuş, IZTECH)

DEU - ADEP TSA-2024-3341, 2024-2026, Development of Ocular Surface Squamous Cell Tumoroids and Their Evaluation as In Vitro Drug Testing Platforms

DEU - ADEP TSA 2023-2025, Development of Human Induced Pluripotent Stem Cell-Derived Brain Organoids in a Machine Learning-Supported Microfluidic System

TÜBİTAK 1001 221M774, 2022-2024, Development of Hydrogel-Impregnated Auxetic Knitted Bandages for Use in Sports Injuries (PI: Assoc. Prof. Dr. Gözde Ertekin, Ege University)

TÜSEB-A Group 28778, 2023-2024, Effects of Autophagy in Ocular Structures Developed from Pluripotent Stem Cells

TÜBİTAK 2247A 121C313, 2022–2026, Development of a Morphogenesis-Focused Micro-Physiological Environment for Functional Lacrimal Organoid Generation

European Joint Programme Rare Diseases, TÜBİTAK 121S276, 2021-2024, Aak-Insight_ Innovative Therapeutic Approaches for the Prevention or Treatment of Aniridia-Associated Corneal Opacification

TÜBİTAK 1003 218S989, 2020-2025, Development of Corneal Endothelium Tissue via Stem Cell and Bioengineering Approaches

TÜBİTAK 1003 318S208, 2019-2021, Development of a Novel Topical Therapy for Macular Corneal Dystrophy

TÜBİTAK 1001 217S654, 2018-2020, Development of Induced Pluripotent Stem Cell (iPSC)-Derived Corneal Organoid Models

TÜBİTAK 1001 117S264, 2017-2019, Development of Lacrimal Gland Using Stem Cells through Tissue Engineering Approaches

TÜBİTAK 3501 118S477, 2018-2020, Development of Osteogenic Niche Under Dynamic Culture Conditions Using Microfluidic Bioreactors

TÜBİTAK 2232 115C125, 2015-2017, Development of a Bone-Cartilage Interface Model in Microfluidic Chips Using Tissue Engineering Approaches with Stem Cells

Patents

Chen P, Demirci U, Güven S, Scaffold-free 3D cell assembly based on patterned hydrodynamic drag force, US10465161B2

Anchan RM, Guven S, Demirci U, Mutter GL, Methods relating to cryopreservation, US20190366330A1

Team

Active Members

Prof. Dr. Canan Aslı Yıldırım
Assoc. Prof. Dr. Onur Başçı
Tuğba Topbaş
Burak Kahveci
Özge Süer
Hülya Erboğa
Mustafa Titiz
Smyrna Ergönül
Semih Numan Göçmez
Gaye Su Yiğit
Beyza Aktaş
Şeyma Akgül
Gizem Sevinç
Aslı Ceren Ekici