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

Principle aim of the project is the development of a transplantable tissue container which enables the in vivo production of recombinant therapeutic proteins for the treatment of autoimmune diseases and cancer. As a model biological TNFR2-Fc is used which corresponds to the clinically approved TNF-blocker Enbrel®.

In the first funding period bioinks supplemented with TNFR2-Fc producer cells have been developed, which will now be used to print structured containers or container inlets enabling accelerated in vivo vascularization. This should allow durable and stable biological production and release in vivo. The effectiveness of the therapeutic tissue container will be assessed in the pristan induced rat arthritis model.

Prof. Dr. Dr. h.c. Raymund Horch
Prof. Dr. Harald Wajant

Yvonne Kulicke

Previous academic education:
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: Yvonne.Kulicke@uk-erlangen.de

 

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

 

Dr. Isabell Lang

Previous academic education: Postdoctoral fellow
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: -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

 

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)

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)

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)

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)

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)

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)

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)

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)

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

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)

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