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INSTITUTE FOR BIOFUNCTIONAL POLYMER MATERIALS

Tissue and Tumour Microenvironments

Our research has evolved at the interface between Tissue Engineering and Cell Biology. By applying tissue engineering principles to cancer research, we pioneer the new discipline of Tumour Tissue Engineering. 

Daniela Lössner

BIOMATERIALS

We use and develop different biomaterials to produce modular tissue culture platforms. For example, gelatin methacryloyl (GelMA) is a covalently photo-crosslinked hydrogel and based on the functionalisation of gelatin with methacrylamide. GelMA’s key advantages are its biodegradability, control over its composition and biomechanical properties to replicate tissue-like features. We also work with polyethylene glycol and peptide-protein co-assembling matrices.

Schematic illustrating of GelMA production, cell encapsulation and application as 3D bioassays. Source: Meinert C, Theodoropoulos C,Klein TJ, Hutmacher DW, Loessner D.cA method for prostate and breast cancer cell spheroid cultures using gelatin methacryloyl-based hydrogels. In: Prostate Cancer. Methods in Molecular Biology 1786: 175-194, 2018.

TISSUE AND TUMOUR MICROENVIRONMENTS

We are interested in understanding the extracellular and cellular communication in diseases like cancer and therapy responses by applying different biomaterials and tissue engineering principles. We are developing new technologies for modelling the human disease in the laboratory. To find better therapies, we design patient-specific models that mimic the composition and biomechanics of tumour tissues and target interactions between cells.

Schematic illustrating the combined approach of hydrogels and fibrous scaffolds to model the ovarian tumour microenvironment. Source: Loessner D, Rockstroh A, Shokoohmand A, Holzapfel BM, Wagner F, Baldwin J, Boxberg M, Schmalfeldt B, Lengyel E, Clements JA, Hutmacher DW. A 3D tumour microenvironment regulates cell proliferation, peritoneal growth and expression patterns. Biomaterials 190-191: 63-75, 2019.

FUNDING

  • ERC Consolidator Grant (CoG), LS9



CONTACT

Daniela Lössner

loessner@ipfdd.de



TISSUE ENGINEERING

We use and fabricate tissue-engineered constructs that integrate extracellular matrix, molecular and biomechanical properties to grow functional tissues. For example, polycaprolactone (PCL) is used for melt electrospinning writing, a 3D printing technique, to generate scaffolds that allow the attachment of tissue-specific cell types. These PCL scaffolds provide a fibrous network and structural support for cell infiltration to mimic characteristic parameters of tissue-like features.

The endosteal niche is recreated using melt electrospun written scaffolds seeded with human primary osteoblasts, which deposit and express extracellular matrix proteins. Source: Muerza-Cascante ML, Koshrotehrani K, Haylock D, Hutmacher DW, Loessner D. Engineering the haematopoietic stem cell niche in vitro. In: Comprehensive Biomaterials II. Elsevier. Vol.5 (2nd ed.): 187-199, 2017.

CANCER

In an interdisciplinary setting, we design 3D approaches that deconstruct the native tissue composition and biomechanical properties of different tumour types to provide clinically predictive platforms and to test novel treatments. Therefore, we study the tumour biology and treatment responses of primary tumours, such as pancreatic cancer, ovarian cancer, colon cancer, neuroblastoma and osteosarcoma, as well as metastases, including peritoneal, prostate and breast cancer-induced metastasis.

 

 

SELECTED PUBLICATIONS (since 2016)

  • Tomás-Bort E, Kieler M, Sharma S, Candido JB, Loessner D. 3D approaches to model the tumor microenvironment of pancreatic cancer. Theranostics 10(11): 5074-5089, 2020. doi: 10.7150/thno.42441.
  • Hedegaard CL, Redondo-Gómez C, Tan BY, Ng KW, Loessner D, Mata A. Peptide-protein co-assembling matrices as a biomimetic 3D model of ovarian cancer. Science Advances 6(40): eabb3298, 2020. doi: 10.1126/sciadv.abb3298.
  • Loessner D, Rockstroh A, Shokoohmand A, Holzapfel BM, Wagner F, Baldwin J, Boxberg M, Schmalfeldt B, Lengyel E, Clements JA, Hutmacher DW. A 3D tumor microenvironment regulates cell proliferation, peritoneal growth and expression patterns. Biomaterials 190-191: 63-75, 2019. doi: 10.1016/j.biomaterials.2018.10.014.
  • Wang P, Magdolen V, Seidl C, Dorn J, Drecoll E, Kotzsch M, Yang F, Schmitt M, Schilling O, Rockstroh A, Clements JA, Loessner D. Kallikrein-related peptidases 4, 5, 6 and 7 regulate tumor-associated factors in serous ovarian cancer. British Journal of Cancer 119(7): 1-9, 2018. doi: 10.1038/s41416-018-0260-1.
  • Muerza-Cascante ML, Shokoohmand A, Koshrotehrani K, Haylock D, Dalton PD, Hutmacher DW, Loessner D. Endosteal-like extracellular matrix expression on melt electrospun written scaffolds. Acta Biomaterialia 52: 145-158, 2017. doi: 10.1016/j.actbio.2016.12.040.
  • Loessner D, Meinert C, Kaemmerer E, Martine LC, Yue K, Levett PA, Klein TJ, Melchels FP, Khademhosseini A, Hutmacher DW. Functionalization, preparation and use of cell-laden gelatin methacryloyl-based hydrogels as modular tissue culture platforms. Nature Protocols 11(4): 727-746, 2016. doi: 10.1038/nprot.2016.037.