Regenerative Medicine Utrecht

Internships for Master students

Collaborative project: Biofabrication facility and Experimental Urology

Tissue engineering (TE) and 3D bioprinting could provide an alternative that would help solve the shortage of tissue in reconstruction surgery. Although great progress has been made so far with TE from various cell sources (stem and progenitor cells, iPS cells, and organoids)1-3 and different bioprinting techniques4, ex vivo engineered living grafts remain limited in size. Living tissue that exceeds 200-400 μm in dimension needs to be functionally vascularized and perfused to ensure cellular survival.5 Natural blood vessel formation is tightly regulated, relying on an organized chronological order of growth, maturation, the suppression of continuous expansion, and introduction of vascular quiescence, which is orchestrated by a complex interplay of different biological factors.6 The natural specialized extracellular matrix (ECM) of the vasculature not only provides a structural framework, but is also critical for regulation of cell behaviour, including adhesion, proliferation, migration and differentiation.7 By mixing ECM components in (gelatin based) hydrogels we may be able to bio-functionalize these hydrogels and induce vascularization.

Our group is interested in TE for urethral reconstruction purposes, performed in patients with urethral strictures or congenital disorders. Challenges in our research are to induce regeneration of the tissue without inducing fibrosis, generating a barrier for urine and preserve erectile function of the penis. As the corpus spongiosum (CS) is an integral part of the urethra and important in supporting the function of the urethra, TE of the urethra should be combined with reconstruction of the CS8. The CS can be regarded as a spongy vessel, therefore the ECM of the CS should provide us with queues for vascularization.

This project focusses on the ECM of the CS, we have isolated ECM of healthy and fibrotic CS and subjected this to proteomic analysis. Furthermore, we have generated ECM gels to grow cells in or to bio-functionalize gelatin based hydrogels. Our aim is to analyze the proteomic data for identification of genes that will lead to healthy regeneration of the CS, and the genes that induce chronic inflammation of the CS, leading to a fibrotic state in case of urethral stricture disease. Moreover, we will grow cells in hydrogels enriched with ECM components of the CS to test the formation of vascular networks.

We are looking for a Master student with strong interest in translational science, who is skilled, both practical as in communication, open and independent. We offer an insight in urology with a direct link to the clinic, a variety of techniques and challenging science. Techniques used in the internship are cell culture (3D in hydrogels, but also 2D in combination with transfection of expression constructs or siRNA), data analysis, qPCR, (immuno)histochemistry, microscopy, western blot, biomechanical testing and biofabrication techniques (3D hydrogel printing).

For more information, please contact Dr. Petra de Graaf (p.degraaf-4@umcutrecht.nl)

1. Kimbrel EA, Lanza R. Nat Rev Drug Discov 2015; 14(10): 681-92.
2. Kobolak J, Dinnyes A, Memic A, et al. Methods 2016; 99: 62-8.
3. Lancaster MA, Knoblich JA. Science 2014; 345(6194): 1247125.
4. Chia HN, Wu BM. J Biol Eng; 9: 4.
5. Auger FA, Gibot L, Lacroix D. Annu Rev Biomed Eng; 15: 177-200.
6. Park KM, Gerecht S. Development; 141(14): 2760-9.
7. Davis GE, Senger DR. Circ Res 2005; 97(11): 1093-107.
8. de Kemp V, de Graaf P, Fledderus JO, et al. PloS one 2015; 10(2): e0118653.

Click here to download a description of the RMT or BioFab project.