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C04 | Biofabrication of cellularized and by the AV loop vascularized tissue container for the transplantation of cells producing therapeutic proteins

The primary goal of project C04 is the development of a transplantable therapeutic container for the in vivo production and release of recombinant proteins. This container consists of an inert shell with a biofabricated matrix enabling the growth of a biologic-secreting cell line. The long-term survival of the producing cells, and thus the continuous secretion of the biologic and its transport into the bloodstream, is achieved through in vivo vascularization via an arteriovenous (AV) loop. The applicability of the therapeutic tissue container will be assessed in project C04 in a rat breast cancer model with a TRAIL death receptor-agonist producing tissue container.

PD Dr. med. sci. Theresa Promny
Prof. Dr. Harald Wajant

Jonas Deinlein

Previous academic education: Master of Science (M.Sc.) in Biochemistry
Academic Advisor within CRC/TRR225: Prof. Dr. Harald Wajant
Location: University Hospital Würzburg, Division of Molecular Internal Medicine Department for Internal Medicine II
Topic of thesis: Modifying bioinks with TRAILR and TWEAK agonists
Main techniques and methodologies to be used: Ink modification, generation producer cell lines, 2D Cell Culture, Western Blot, ELISA, qPCR
Contact: deinlein_j@ukw.de

Dr. Isabell Lang

Previous academic education: Postdoctoral fellow
Academic Advisor within CRC/TRR225: Prof. Dr. Harald Wajant
Location: University Hospital Würzburg, Division of Molecular Internal Medicine Department for Internal Medicine II
Topic of thesis: -Characteriziation and generation of new producer cell lines, -Analysis of “danger”-signal release from producing cells
Main techniques and methodologies to be used: GpL fusion proteins as tracers, Ink modification, functional AuNPs
Contact: lang_i@ukw.de

Yvonne Kulicke

Previous academic education: Master of Science (M.Sc.) in Biology
Academic Advisor within CRC/TRR225: Prof. Dr. Dr. Raymund E. Horch
Location: Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Department of Plastic and Hand Surgery University Hospital of Erlangen
Topic of thesis: Generation of bioactive tissue containers in the rat AV loop model
Main techniques and methodologies to be used: microsurgical operations (rat), histology, µCT and molecular biological analyses
Contact: Yvonne.Kulicke@uk-erlangen.de

2026

Weinhold CM, Heltmann-Meyer S, Ng XJ, Scheibel T, Fey T, Wajant H, Geppert C, Arkudas A, Steiner D, Horch RE. Biofabrication of Endothelialized, Intrinsically Vascularized 3D-Printed Recombinant Spider Silk Scaffolds. Advanced Healthcare Materials, doi: 10.1002/adhm.202504883 (2025). (C04, C01)

2025

Heltmann-Meyer S, Detsch R, Hazur J, Kling L, Pechmann S, Kolan R, Osterloh J, Boccaccini A, Christiansen S, Geppert C, Arkudas A, Horch R, Steiner D. Biofunctionalization of ADA-GEL Hydrogels Based on the Degree of Cross-Linking and Polymer Concentration Improves Angiogenesis. Adv. Healthcare Mat. 14(11), doi:10.1002/adhm.202500730 (2025). (C04, A01, B06)

Heltmann-Meyer S, Fleischer S, Kadam S, Boccaccini AR, Kirmsse S, Forster L, Teßmar J, Schrüfer S, Lamberger Z, Stahlhut P, Lang G, Boßerhoff AK, Arkudas A, Horch RE, Kengelbach-Weigand A, Schmid R. Ink comparison for extrusion-based bioprinting in the context of breast cancer and melanoma models. International Journal of Bioprinting, doi: 10.36922/ijb.5828 (2025). (C03, A01, A02, A07, C04).

Osterloh J, Heltmann-Meyer S, Trossmann VT, Cai A, Kulicke Y, Terörde K, Sörgel CA, Lang I , Wajant H , Scheibel T, Fey T, Steiner D, Arkudas A, Horch RE. In Vivo Vascularization of Cell-Supplemented Spider Silk-Based Hydrogels in the Arteriovenous Loop Model. Biomimetics (Basel), 10, doi: 10.3390/biomimetics10020117 (2025). (C04, C01)

Sandor E, Karimi T, Schmid R, Kulicke Y, Heltmann-Meyer S, Eckert C, Schmidt S, Röder J, Boccaccini A, Horch R, Boßerhoff A, Kengelbach-Weigand A, Arkudas A. Biofabrication of 3D printed, pre-cross-linked alginate dialdehyde-gelatin (ADA-GEL) scaffolds for the in vivo metastatic Arteriovenous loop tumor model. Frontiers in Bioengineering and Biotechnology. doi: 10.3389/fbioe.2025.1657653 (2025). (C03, C04, A01)

Schmid R, Kulicke Y, Sandor E, Lu H-H, Fleischer S, Lang I, Wajant H, Kankova H, Arkudas A, Kengelbach-Weigand A, Horch R E, Boccaccini A R, Promny T. Assessing angiogenic properties in vitro or in ovo of pre-crosslinked alginate-dialdehyde-gelatine (ADA-GEL) hydrogels incorporating boron-doped mesoporous bioactive glass particles. Adv Nanobiomed Res, doi: 10.1002/anbr.202500143 (2025). (C04, C03, B03)

2024

Bettendorf E, Schmid R, Horch RE, Kengelbach-Weigand A, Kulike Y, Schrüfer S, Schubert DW, Lamberger Z, Stahlhut P, Lang G, Sörgel CA. Bioprinted keratinocyte and stem cell laden constructs for skin tissue engineering. IJB doi: 10.36922/ijb.3925 (2024). (C03, A07, C04)

Schmid R, Schmidt SK, Schrüfer S, Schubert DW, Heltmann-Meyer S, Schicht M, Paulsen F, Horch RE, Bosserhoff AK, Kengelbach-Weigand A, Arkudas A: A vascularized in vivo melanoma model suitable for metastasis research of different tumor stages using fundamentally different bioinks; Materials Today Bio 26 (2024) 101071; doi: 10.1016/j.mtbio.2024.101071 (2024). (A07, C03, C04, Z03)

Schipka R, Heltmann-Meyer S, Schneidereit D, Friedrich O, Röder J, Boccaccini AR, Schrüfer S, Schubert DW, Horch RE, Bosserhoff AK, Arkudas A, Kengelbach-Weigand A, Schmid R: Characterization of two different alginate-based bioinks and the influence of melanoma growth within. NaturePortfolio, Scientific Reports doi.org/10.1038/s41598-024-63642-3 (2024). (C03, A01, A07, B08, C04, Z03)

2023

Schulik J, Salehi S, Boccaccini AR, Schrüfer S, Schubert DW, Arkudas A, Kengelbach-Weigand A, Horch RE, Schmid R, Comparison of the Behavior of 3D-Printed Endothelial Cells in Different Bioinks, Bioengineering 10(7) (2023). (C03, A07, C04, B03)

Sörgel CA, Cai A, Schmid R, Horch RE. Perspectives on the Current State of Bioprinted Skin Substitutes for Wound Healing. Biomedicines, doi: 10.3390/biomedicines11102678 (2023). (C03, C04)

Vaghela R, Arkudas A, Gage D, Korner C, von Horsten S, Salehi S, Horch RE, Hessenauer M, A Novel Window into Angiogenesis-Intravital Microscopy in the AV-Loop-Model, Cells 12(2) (2023). (B03, C03, C04)

2022

Trossmann VT, Heltmann-Meyer S, Amouei H, Wajant H, Horch RE, Steiner D, Scheibel T, Recombinant Spider Silk Bioinks for Continuous Protein Release by Encapsulated Producer Cells, Biomacromolecules doi:10.1021/acs.biomac.2c00971  (2022). (C01, C04)

Vaghela R, Arkudas A, Gage D, Korner C, von Horsten S, Salehi S, Horch RE, Hessenauer M, Microvascular development in the rat arteriovenous loop model in vivo-A step by step intravital microscopy analysis, J Biomed Mater Res A doi:10.1002/jbm.a.37395 (2022). (B03, C04)

Steiner D, Reinhardt L, Fischer L, Popp V, Korner C, Geppert CI, Bauerle T, Horch RE, Arkudas A, Impact of Endothelial Progenitor Cells in the Vascularization of Osteogenic Scaffolds, Cells 11(6) (2022). (C04)

Sörgel CA, Schmid R, Stadelmann N, Weisbach V, Distel L, Horch RE, Kengelbach-Weigand A, IGF-I and Hyaluronic Acid Mitigate the Negative Effect of Irradiation on Human Skin Keratinocytes, Cancers 14(3) (2022). (C03, C04)

Ritter P, Cai A, Reischl B, Fiedler M, Prol G, Frie B, Kretzschmar E, Michael M, Hartmann K, Lesko C, Salti H, Arkudas A, Horch R, Paulsen F, Friedrich O, Haug M, MyoBio: An automated bioreactor system technology for standardized perfusion-decellularization of whole skeletal muscle, IEEE Trans Biomed Eng PP (2022). (B08, C04)

2021

Schmid R, Schmidt SK, Detsch R, Horder H, Blunk T, Schrüfer S, Schubert DW, Fischer L, Thievessen I, Heltmann‐Meyer S, Steiner D, Schneidereit D, Friedrich O, Grüneboom A, Amouei H, Wajant H, Horch RE, Bosserhoff AK, Arkudas A, Kengelbach‐Weigand A, A New Printable Alginate/Hyaluronic Acid/Gelatin Hydrogel Suitable for Biofabrication of In Vitro and In Vivo Metastatic Melanoma Models, Adv. Funct. Mater. doi:10.1002/adfm.202107993 (2021). (C03, A01, A07, B06, B08, C02, C04)

Steiner D, Mutschall H, Winkler S, Horch RE, Arkudas A, The Adipose-Derived Stem Cell and Endothelial Cell Coculture System-Role of Growth Factors?, Cells 10(8) (2021). (C04)

Heltmann-Meyer S, Steiner D, Muller C, Schneidereit D, Friedrich O, Salehi S, Engel FB, Arkudas A, Horch RE, Gelatin methacryloyl is a slow degrading material allowing vascularization and long-term usein vivo, Biomed Mater 16(6) (2021). (B03, B08, C01, C04)

Winkler S, Mutschall H, Biggemann J, Fey T, Greil P, Korner C, Weisbach V, Meyer-Lindenberg A, Arkudas A, Horch RE, Steiner D, Human Umbilical Vein Endothelial Cell Support Bone Formation of Adipose-Derived Stem Cell-Loaded and 3D-Printed Osteogenic Matrices in the Arteriovenous Loop Model, Tissue Eng Part A 27(5-6) (2021) 413-423. (C04, C03)

 Steiner D, Winkler S, Heltmann-Meyer S, Trossmann V, Fey T, Scheibel T, Horch RE, Arkudas A, Enhanced vascularization andde novotissue formation in hydrogels made of engineered RGD-tagged spider silk proteins in the arteriovenous loop model, Biofabrication doi:10.1088/1758-5090/ac0d9b  (2021). (C01, C04)

Hessenauer MET, Vaghela R, Korner C, von Horsten S, Pobel C, Gage D, Muller C, Salehi S, Horch RE, Arkudas A, Watching the vessels grow – establishment of intravital microscopy in the AV-loop rat model, Tissue Eng Part C Methods doi:10.1089/ten.TEC.2021.0024  (2021). (C04, B03)

2020

Tolksdorf J, Horch RE, Gruner JS, Schmid R, Kengelbach-Weigand A, Schubert DW, Werner S, Schneidereit D, Friedrich O, Ludolph I, Size matters-in vitro behaviour of human fibroblasts on textured silicone surfaces with different pore sizes, J. Mater. Sci.: Mater. Med. 31(2) (2020) 23. (C04, B08, A07, C03)

Mutschall H, Winkler S, Weisbach V, Arkudas A, Horch RE, Steiner D, Bone tissue engineering using adipose-derived stem cells and endothelial cells: Effects of the cell ratio, J. Cell. Mol. Med. 24(12) (2020) 7034-7043. (C04, C03)

2019

Steiner D, Lang G, Fischer L, Winkler S, Fey T, Greil P, Scheibel T, Horch RE, Arkudas A, Intrinsic Vascularization of Recombinant eADF4(C16) Spider Silk Matrices in the Arteriovenous Loop Model, Tissue Eng Part A 25(21-22) (2019) 1504-1513. (C04, A07, C01, C03)

2018

Weigand A, Horch RE, Boos AM, Beier JP, Arkudas A, The Arteriovenous Loop: Engineering of Axially Vascularized Tissue, Eur. Surg. Res. 59(3-4) (2018) 286-299. (C03, C04)

Steiner D, Lingens L, Fischer L, Kohn K, Detsch R, Boccaccini AR, Fey T, Greil P, Weis C, Beier JP, Horch RE, Arkudas A, Encapsulation of Mesenchymal Stem Cells Improves Vascularization of Alginate-Based Scaffolds, Tissue Eng Part A 24(17-18) (2018) 1320-1331. (C03, C04, A01, B06, B03) Front Cover for Tissue Engineering Part A

Rottensteiner-Brandl U, Detsch R, Sarker B, Lingens L, Kohn K, Kneser U, Bosserhoff AK, Horch RE, Boccaccini AR, Arkudas A, Encapsulation of Rat Bone Marrow Derived Mesenchymal Stem Cells in Alginate Dialdehyde/Gelatin Microbeads with and without Nanoscaled Bioactive Glass for In Vivo Bone Tissue Engineering, Materials (Basel) 11(10) (2018) 1880. (C04, A01, C03)

Horch RE, Weigand A, Wajant H, Groll J, Boccaccini AR, Arkudas A, [Biofabrication: new approaches for tissue regeneration], Handchir Mikrochir Plast Chir 50(2) (2018) 93-100. (C04)

2025

Horch RE
Organizing Committee of TERMIS-AP 2025
TERMIS Asia-Pacific Conference 2025, 16th- 19th October 2025, Wuhan (China)

2021

Schmid R, Schmidt SK, Detsch R, Horder H, Blunk T, Schrüfer S, Schubert DW, Fischer L, Thievessen I, Heltmann-Meyer S, Steiner D, Schneidereit D, Friedrich O, Grüneboom A, Amouei H, Wajant H, Horch RE, Bosserhoff AK, Arkudas A, Kengelbach-Weigand A (2021)
A new printable alginate / hyaluronic acid / gelatin hydrogel suitable for biofabrication of in vitro and in vivo metastatic melanoma models
31st Annual Conference of the European Society for Biomaterials (ESB 2021), 5 to 9 September 2021 (C03, A01, A07, B06, B08, C02, C04)

2019

Winkler S, Steiner D, Biggemann J, Fey T, Greil P, Körner C, Weisbach V, Meyer-Lindenberg A, Mutschall H, Arkudas A and Horch RE (2019)
Intrinsic vascularization of ADSC-loaded hydrogel scaffolds in the rat AV loop model
The 11th EPSRC Meeting, 23-25 August 2019, Munich, Germany, Klinikum rechts der Isar, Technische Universität München (München, Germany)

Heltmann-Meyer S (2019)
Biofabrikation zellularisierter und im AV Loop vaskularisierter Gewebecontainer für die Transplantation wirkstoffproduzierender Zellen
3. DAM Wissenschaftsakademie, 12 – 13 April 2019 (Erlangen, Germany)

2018

Peddi A, Steiner D, Weigand A, Lingens L, Fischer L, Köhn K, Detsch R, Boccaccini AR, Fey T, Greil P, Weis C, Beier JP, Horch RE, Arkudas A. (2018)
Encapsulation of mesenchymal stem cells improves vascularization of alginate-based scaffolds
The 10th EPSRC Meeting, 23 – 25 August 2018 (Hamburg, Germany)

Heltmann-Meyer S, Steiner D, Lang G, Winkler S, Fischer L, Fey T, Greil P, Scheibel T, Horch RE, Arkudas A. (2018)
Intrinsic Vascularization of Recombinant eADF4(C16) Spider Silk fibrous matrices in the Arteriovenous Loop Model
10th EPSRC Meeting, 23 – 25 August 2018 (Hamburg, Germany)

2022

Rafael Schmid, Sonja K. Schmidt, Rainer Detsch, Hannes Horder, Torsten Blunk, Stefan Schrüfer, Dirk W. Schubert, Lena Fischer, Ingo Thievessen, Stefanie Heltmann-Meyer, Dominik Steiner, Dominik Schneidereit, Oliver Friedrich, Anika Grüneboom, Hanna Amouei, Harald Wajant, Raymund E. Horch, Anja K. Bosserhoff, Andreas Arkudas, Annika Kengelbach-Weigand
A New Printable Alginate/Hyaluronic Acid/Gelatin Hydrogel Suitable for Biofabrication of In Vitro and In Vivo
Metastatic Melanoma Models TERMIS EU 2022               C03 and A01, A07, B06, B08, C02, C04

2020

Trossmann V, Steiner D, Heltmann-Meyer S, Winkler S, Amouei H, Wajant H, Fey T, Greil P, Scheibel T, Arkudas A, Horch RE
Establishment of a fiber-based and RGD-modified spider silk for the generation of a drug-producing tissue container
5th Bioinspired Materials 2020 Conference, 16 – 19 March 2020 – Web conference

2018

Weigand A, Boos AM, An R, Strissel PL, Schmid R, Robering JW, Al-Abboodi M, Detsch R, Dalton PD, Youssef A , Boccaccini AR, Beckmann MW, Bäuerle T, Strick R, Horch RE (2018)
From Tissue Engineering to Tumor Engineering –  Application of the arteriovenous loop model for the generation of a fully vascularized tumor in an animal model
2018 TERMIS World Congress, 4-7 September 2018 (Kyoto, Japan)

Hanna Amouei

Previous academic education: Master
Academic Advisor within SFB TRR225: Prof. Dr. Harald Wajant
Location: University Hospital Würzburg, Division of Molecular Internal Medicine Department for Internal Medicine II
Topic of thesis: Development of structured, cell-doted matrices for the “in vivo” production of biologicals
Main techniques and methodologies to be used: GpL fusion proteins as tracers, Development of producer cell lines, Ink, structure  and print protocol evaluation

Contact: hanna.amouei@uni-wuerzburg.de

Stefanie Heltmann-Meyer

Previous academic education: Master
Academic Advisor within SFB TRR225: Prof. Dr. Dr. Raymund E. Horch
Location: Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Department of Plastic and Hand Surgery University Hospital of Erlangen
Topic of thesis: Generation of bioactive tissue containers in the rat AV loop model
Main techniques and methodologies to be used: microsurgical operations (rat), histological and molecular biological analyses of the explants

Contact: stefanie.heltmann-meyer@uk-erlangen.de

Klara Terörde

Advisor within SFB TRR225: Prof. Dr. Dr. Raymund E. Horch
Location: Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Department of Plastic and Hand Surgery University Hospital of Erlangen

Dr. Justus Osterloh

Previous academic education: Postdoc, M.D.
Academic Advisor within SFB TRR225: Prof. Dr. Dr. Raymund E. Horch
Location: Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Department of Plastic and Hand Surgery University Hospital of Erlangen
Main techniques and methodologies to be used: microsurgical operations (rat), histology, µCT and molecular biological analyses

Contact: justus.osterloh@uk-erlangen.de

PD Dr. med. sci. Theresa Promny

Prof. Dr. Harald Wajant

  • Editorial Board Member Cellular Signaling
  • Editorial Board Member Cell Death & Differentiation