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A02 | Hyaluronic acid-based bioink platform with multi-functional crosslinkers for the controlled differentiation of mesenchymal stem cells

Hyaluronic acid (HA) represents a major component of the human extracellular matrix, however, so far highly versatile HA-based materials for biofabrication are lacking. The overall aim of this project is to develop a HA-based bioink platform utilizing multi-functional crosslinkers (PEG, modified biopolymers) that enables the controlled differentiation of mesenchymal stem cells. The modification with peptides and growth factors as well as the processing into gradient materials will further promote the development of coherent tissues within the printed 3D constructs. For the long term, this work aims to generate bioinks for the development of clinically relevant tissue models.

Prof. Dr. Torsten Blunk
Dr. habil. Jörg Teßmar

Jeanette Weigelt

Previous academic education: B.Sc. Chemistry 2018, Master thesis in chemistry 2021
Academic Advisor within SFB/TRR 225: Dr. habil Jörg Tessmar
Location: University of Würzburg, Department for Functional Materials in Medicine and Dentistry
Topic of thesis: Hyaluronic acid based bioinks for biofabrication of mesenchymal stem cells
Main techniques and methodologies to be used: Synthesis, spectroscopy, gelation, rheometry, 3D bioprinting

Contact: jeanette.weigelt@uni-wuerzburg.de

Paula Büttner

Previous academic education: M. Sc. Biomedicine
Academic Advisor within SFB/TRR 225:  Prof. Dr. Torsten Blunk
Location: University Hospital Würzburg, Department of Trauma, Hand, Plastic and Reconstructive Surgery
Topic of thesis: Hyaluronic Acid Hydrogels for Biofabrication to control Differentiation of Mesenchymal Stromal Cells
Main techniques and methodologies to be used: 2D/3D Tissue Culture, Histology, Immunohistochemistry, Microscopy, qRT-PCR, quantitative DNA- and ECM-Assays, Western Blotting

Contact: Buettner_P1@ukw.de

2025

Andrade Mier MS, Türker E, Faber J, Friedrich M, Lamberger Z, Weigelt J, Suwannakot P, Gantert B, Singh A, Moessler V, Sodmann A, Murenu N, Schenk J, Schaefer N, Blunk T, Boccaccini AR, Lühmann TC, Tessmar J, Crook JM, Tomaskovic-Crook E, Dalton PD, Lang G, Blum R, Strick R, Budday S, Heinze KG, Villmann C. 3D In Vitro Glioma‐Neuron‐Astrocyte Biomimetic Composites Recapitulate Key Molecular Mechanisms Linked to Glioblastoma Multiforme Pathophysiology. Advanced Functional Materials, doi: 10.1002/adfm.202419211 (2025). (A01, A02, A07, B06, B09, C02, C05, Z02)

Faber J, Greiner A, Büttner P, Schoppe C, Bräuer L, Paulsen F, Blunk T, Perl M, Betsch M, Budday S. Poro-viscoelastic mechanical characterization of healthy and osteoarthritic human articular cartilage. Journal of the Mechanical Behavior of Biomedical Materials 173, doi: 10.1016/j.jmbbm.2025.107226 (2025). (A02, B09)

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).

2024

Horder H, Böhringer D, Endrizzi N, Hildebrand LS, Cianciosi A, Stecher S, DusiF, Schweinitzer S, Watzling M, Groll J,  Jüngst T, Teßmar L, Bauer-Kreisel P, Fabry B, Torsten B. Cancer cell migration depends on adjacent ASC and adipose spheroids in a 3D bioprinted breast cancer model. Biofabrication doi: 10.1088/1758-5090/ad57f7 (2024). (C02, A01, A02, B09)

Karakaya E, Gleichauf L, Schöbel L, Hassan A, Soufivand AA, Tessmar J, Budday S,  Boccaccini AR, Detsch R. Engineering peptide-modified alginate-based bioinks with cell-adhesive properties for biofabrication. RSC Adv. doi: 10.1039/D3RA08394B. (2024). (B06, A02, A01, B09)

Türker E, Andrade Mier MS, Faber J, Padilla Padilla SJ, Murenu N, Stahlhut P, Lang G, Lamberger Z, Weigelt J, Schaefer N, Tessmar J, Strissel PL, Blunk T, Budday S, Strick R, Villmann C. Breast tumor cell survival and morphology in a brain-like extracellular matrix depends onmatrix composition and mechanical properties. Adv Biol doi: 10.1002/adbi.202400184. (2024) (A02, A07, B09, C02, C05)

2023

Karakaya E, Schobel L, Zhong Y, Hazur J, Heid S, Forster L, Tessmar J, Boccaccini AR, Detsch R, How to Determine a Suitable Alginate for Biofabrication Approaches using an Extensive Alginate Library?, Biomacromolecules doi:10.1021/acs.biomac.2c01282  (2023). (B06, A02, A01)

2022

Brand JS, Forster L, Bock T, Stahlhut P, Tessmar J, Groll J, Albrecht K, Covalently Cross-Linked Pig Gastric Mucin Hydrogels Prepared by Radical-Based Chain-Growth and Thiol-ene Mechanisms, Macromol Biosci 22(4) (2022) e2100274. (B07, A02, A06)

Janzen D, Bakirci E, Faber J, Mier MA, Hauptstein J, Pal A, Forster L, Hazur J, Boccaccini AR, Detsch R, Tessmar J, Budday S, Blunk T, Dalton PD, Villmann C, Reinforced Hyaluronic acid-based Matrices promote 3D Neuronal Network Formation, Adv Healthc Mater doi:10.1002/adhm.202201826  (2022) e2201826. (A01, A02, B06, B09, B01/C05)

Karakaya E, Bider F, Frank A, Teßmar J, Schöbel L, Forster L, Schrüfer S, Schmidt H-W, Schubert DW, Blaeser A, Boccaccini AR, Detsch R, Targeted Printing of Cells: Evaluation of ADA-PEG Bioinks for Drop on Demand Approaches, Gels 8(4) (2022). (B06, A02, A04, A07)

Hauptstein J, Forster L, Nadernezhad A, Groll J, Teßmar J, Blunk T, Tethered TGF-β1 in a Hyaluronic Acid-Based Bioink for Bioprinting Cartilaginous Tissues, International Journal of Molecular Sciences 23(2) (2022). (A02, A06, B02)

Hauptstein J, Forster L, Nadernezhad A, Horder H, Stahlhut P, Groll J, Blunk T, Tessmar J, Bioink Platform Utilizing Dual-Stage Crosslinking of Hyaluronic Acid Tailored for Chondrogenic Differentiation of Mesenchymal Stromal Cells, Macromol Biosci 22(2) (2022) e2100331. (A02, A06, B02, C02)

2021

Shan J, Bock T, Keller T, Forster L, Blunk T, Groll J, Tessmar J, TEMPO/TCC as a Chemo Selective Alternative for the Oxidation of Hyaluronic Acid, Molecules 26(19) (2021). (A02)

Horder H, Guaza Lasheras M, Grummel N, Nadernezhad A, Herbig J, Ergun S, Tessmar J, Groll J, Fabry B, Bauer-Kreisel P, Blunk T, Bioprinting and Differentiation of Adipose-Derived Stromal Cell Spheroids for a 3D Breast Cancer-Adipose Tissue Model, Cells 10(4) (2021) 803. (C02, A02, B02, B04)

Blum C, Taskin MB, Shan J, Schilling T, Schlegelmilch K, Tessmar J, Groll J, Appreciating the First Line of the Human Innate Immune Defense: A Strategy to Model and Alleviate the Neutrophil Elastase-Mediated Attack toward Bioactivated Biomaterials, Small 17(13) (2021) 2007551. (A06, A02)

Bednarzig V, Karakaya E, Egana AL, Teßmar J, Boccaccini AR, Detsch R, Advanced ADA-GEL bioink for bioprinted artificial cancer models, Bioprinting doi:10.1016/j.bprint.2021.e00145  (2021) 00145. (B06, A01, A02)

Muir VG, Qazi TH, Shan J, Groll J, Burdick JA, Influence of Microgel Fabrication Technique on Granular Hydrogel Properties, ACS Biomater Sci Eng doi:10.1021/acsbiomaterials.0c01612  (2021). (A02, A06)

2020

Schmidt S, Abinzano F, Mensinga A, Tessmar J, Groll J, Malda J, Levato R, Blunk T, Differential Production of Cartilage ECM in 3D Agarose Constructs by Equine Articular Cartilage Progenitor Cells and Mesenchymal Stromal Cells, Int. J. Mol. Sci. 21(19) (2020) 7071. (A02)

Schmid R, Schmidt SK, Hazur J, Detsch R, Maurer E, Boccaccini AR, Hauptstein J, Tessmar J, Blunk T, Schrufer S, Schubert DW, Horch RE, Bosserhoff AK, Arkudas A, Kengelbach-Weigand A, Comparison of Hydrogels for the Development of Well-Defined 3D Cancer Models of Breast Cancer and Melanoma, Cancers 12(8) (2020) 2320. (C03, A01, A02, A07, C02)

Nadernezhad A, Forster L, Netti F, Adler-Abramovich L, Tessmar J, Groll J, Rheological analysis of the interplay between the molecular weight and concentration of hyaluronic acid in formulations of supramolecular HA/FmocFF hybrid hydrogels, Polym. J. 52(8) (2020) 1007-1012. (A02, B04)

Mirzaei Z, Kuth S, Schubert DW, Detsch R, Roether JA, Blunk T, Kordestani SS, Boccaccini AR, Preparation and Characterization of Electrospun Blend Fibrous Polyethylene Oxide:Polycaprolactone Scaffolds to Promote Cartilage Regeneration, Adv. Eng. Mater. 22(9) (2020). (A01, A02, A07, B06)

Mancini IAD, Schmidt S, Brommer H, Pouran B, Schafer S, Tessmar J, Mensinga A, van Rijen MHP, Groll J, Blunk T, Levato R, Malda J, van Weeren PR, A composite hydrogel-3D printed thermoplast osteochondral anchor as example for a zonal approach to cartilage repair: in vivo performance in a long-term equine model, Biofabrication 12(3) (2020) 035028. (A02)

Levato R, Jungst T, Scheuring RG, Blunk T, Groll J, Malda J, From Shape to Function: The Next Step in Bioprinting, Adv. Mater. 32(12) (2020) 1906423. (A02, B04, Z01)

Hazur J, Detsch R, Karakaya E, Kaschta J, Tessmar J, Schneidereit D, Friedrich O, Schubert DW, Boccaccini AR, Improving alginate printability for biofabrication: establishment of a universal and homogeneous pre-crosslinking technique, Biofabrication 12(4) (2020) 045004. (A01, A02, A07, B06, B08)

Hauptstein J, Bock T, Bartolf-Kopp M, Forster L, Stahlhut P, Nadernezhad A, Blahetek G, Zernecke-Madsen A, Detsch R, Jungst T, Groll J, Tessmar J, Blunk T, Hyaluronic Acid-Based Bioink Composition Enabling 3D Bioprinting and Improving Quality of Deposited Cartilaginous Extracellular Matrix, Adv Healthc Mater 9(15) (2020) 2000737. (A02, A06, B02, B06, Z01)

Frischholz S, Berberich O, Bock T, Meffert RH, Blunk T, Resveratrol counteracts IL-1beta-mediated impairment of extracellular matrix deposition in 3D articular chondrocyte constructs, J. Tissue Eng. Regener. Med. 14(7) (2020) 897-908. (A02)

2018

Weis M, Shan J, Kuhlmann M, Jungst T, Tessmar J, Groll J, Evaluation of Hydrogels Based on Oxidized Hyaluronic Acid for Bioprinting, Gels 4(4) (2018) 82. (A02)

Bock T, Schill V, Krahnke M, Steinert AF, Tessmar J, Blunk T, Groll J, TGF-beta1-Modified Hyaluronic Acid/Poly(glycidol) Hydrogels for Chondrogenic Differentiation of Human Mesenchymal Stromal Cells, Macromol. Biosci. 18(7) (2018) 1700390. (A02)

2025

P. Büttner
Post-Fabrication Development of Extracellular Matrix and Mechanical Properties in Cartilaginous Constructs Made from Hyaluronic Acid-based Bioinks
ISBF Biofabrication 2025, 15th September 2025, Warsaw, Poland

Jessica Faber, Alexander Greiner, Paula Büttner, Chiara Schoppe, Lars Bräuer, Friedrich Paulsen, Torsten Blunk, Mario Perl, Marcel Betsch and Silvia Budday
Mechanical characterization of human articular cartilage and cell-laden thiolated hyaluronic acid (HA-SH) hydrogels during chondrogenesis
ICCB 2025, 8th September 2025                                  A02, B09

Jessica Faber, Alexander Greiner, Paula Büttner, Chiara Schoppe, Lars Bräuer, Friedrich Paulsen, Torsten Blunk, Mario Perl, Marcel Betsch and Silvia Budday
Biomechanical characterization of healthy and osteoarthritic human articular cartilage
Workshop Junger Nachwuchswissenschaftler in der Mechanik 2025, 11th March 2025                                  A02, B09

2024

J. Teßmar, J.Weigelt, P. Büttner, L. Forster, J. Hauptstein, T. Blunk
Dual-stage crosslinking hyaluronic acid-based bioinks for bioprinting advanced cartilaginous tissues
World Biomaterials Congress 2024, Daegu, 31.05.2024                   A02

Jörg Teßmar
3D Druck von Organen – Fiktion oder Wirklichkeit?
DPhG Talk LG Niedersachsen in Braunschweig, 25. 06.2024                A02

2022

Dieter Janzen, Ezgi Bakirci, Leonard Forster, Jörg Teßmar, Paul D. Dalton, Carmen Villmann
Neuronal network formation in 3D reinforced hyaluronic-based hydrogels using MEW frames
6th Bioinspired Materials, Kloster Kostenz 2022                     C05, A02

2021

Hauptstein J, Forster L, Nadernezhad A, Groll J, Blunk T, Teßmar J (2021)
Hyaluronic Acid-based Bioink with Dual-stage Crosslinking Mechanism Utilized for Cartilage Tissue Engineering
International Society for Biofabrication ISBF 2021, Wollongong, Australia, online conference (A02, A06, B02)

Horder H, Guaza Lasheras M, Grummel N, Nadernezhad A, Herbig J, Ergün S, Teßmar J, Groll J, Fabry B, Bauer-Kreisel P, Blunk T (2021)
A 3D Bioprinted Breast Cancer-Adipose Tissue Model Utilizing Adipose-Derived Stromal Cell Spheroids
31st Annual Conference of the European Society for Biomaterials (ESB 2021), 5 to 9 September 2021 (A02, B02, B04, C02)

Paulus I, Reineke B, Shan J, Hauschild S, Teßmar J, Förster S, Groll J (2021)
Bioprinting of microfluidic generated microgels based on a degradable and bioactivated POx/GelPA hybrid system
31st Annual Conference of the European Society for Biomaterials (ESB 2021), 5 to 9 September 2021 (virtual) (A06, A02)

2020

Hauptstein J, Böck T, Bartolf-Kopp M, Forster L, Stahlhut P, Nadernezhad A, Blahetek G, Zernecke-Madsen A, Detsch R, Jüngst T, Groll J, Teßmar J, Blunk T (2020)
Hyaluronic Acid-based Bioink Composition Enabling 3D Bioprinting and Improving Quality of Deposited Cartilaginous Extracellular Matrix
Materials Science and Engineering (MSE), 22 – 25 September 2020 – Web conference

Hauptstein J, Bartolf-Kopp M, Forster L, Detsch R, Jüngst T, Groll J, Teßmar J, Blunk T (2020)
Hyaluronic Acid-based Bioink Composition Enabling 3D Bioprinting and Improving Quality of Deposited Cartilaginous Extracellular Matrix
5th Bioinspired Materials 2020 Conference, 16 – 19 March 2020 – Web conference

Tessmar J (2020)
3D-Druck von Organen -Fiktion oder Wirklichkeit?
18.02.2020 Universitätsbund Würzburg Marktheidenfeld, im Raum 3.1 des Alten Rathauses, Marktplatz 24

2019

Shan J, Böck TC, Tessmar J, Groll J (2019)
EMPO Oxidation of Hyaluronic Acid for Stable Hydrogel Formation via Schiff Base Chemistry
30th Annual Conference of the European Society for Biomaterials in tandem with the 26thAnnual Conference of the German Society for Biomaterials (DGBM); September 9 to 13, 2019 (Dresden, Germany)

Jüngst T, Tessmar J, Dalton P, Groll J (2019)
Bionik Development and Melt Electrowriting
Deutsches Zentrum für Luft-und Raumfahrt in Bonn, Workshop Additive Fertigung in der Raumfahrt. 28 May 2019 (Bonn, Germany)

2024

Jeanette Weigelt, Paula Büttner, Torsten Blunk, Jörg Teßmar
Tailoring network properties of a bioink solely made of HA-derivates for cartilaginous tissue bioprinting
Biofabrication 2024, Fukuoka, Japan, 12th November 2024                        A02

2023

Paula Büttner, J. Weigelt, J. Tessmar, J. Groll. T. Blunk
Dual-stage crosslinking bioink solely made from hyaluronic acid components for bioprinting cartilaginous tissue
ISBF Biofabrication 2023 on 18th September 2023

2022

Joerg Teßmar
Dual-Stage Crosslinking HA-based Bioink Platform for Bioprinting Advanced Cartilaginous Tissues B&B_057
Meeting of The International Society for Biofabrication 2022, Montecatini Terme (Italy) on 25-28. September 2022             A02

Paula Büttner, Jeanette Weigelt, Torsten Blunk, Jörg Teßmar
SFB/TRR 225 Project A02: Hyaluronic acid based bioink platform with multi-funcitonal crosslinkers for the controlled differentiation of MSC
Symposium “Biofabrication meets Infection” Würzburg on 25-28. September 2022                   A02

Raphael Lohse, Robin Dai, Hatice Genc, Leonard Forster, Joerg Tessmar, Iwona Cicha
Development of experimental set-up for embedding human endothelial cells and fibroblasts in thiolated hyaluronic acid hydrogels
Meeting of The International Society for Biofabrication 2022, Montecatini Terme (Italy) on 25-28- September 2022                      A02, B02

2021

Hauptstein J, Forster L, Nadernezhad A, Groll J, Blunk T, Teßmar J (2021)
Dual-stage Crosslinked Hyaluronic Acid-based Bioink Tailored for Chondrogenic Differentiation of Mesenchymal Stromal Cells,
31st Annual Conference of the European Society for Biomaterials (ESB 2021), 5 to 9 September 2021 (A02, A06, B02)

2020

Forster L, Hauptstein J, Weichhold J, Nadernezhad A, Böhm TM, Zorn T, Schmidt S, Blunk T, Teßmar J (2020)
Hyaluronic Acid based Hydrogel Platform with MultifuctionalCrosslinkers for the Controlled Differentiation of Mesenchymal Stem Cells
5th Bioinspired Materials 2020 Conference, 16 – 19 March 2020 – Web conference

2019

Karakaya E, Hazur J, Teßmar J, Boccaccini AR, Detsch R(2019)
How to Determine a Suitable Sodium Alginate for the Fabrication of Standardized Alginatedialdehyde-Gelatin crosslinked Hydrogels in Biofabrication Approaches?
Annual Conference of the International Society for Biofabrication (ISBF), 20-22 October 2019 (Columbus, Ohio, USA)

Schmidt S, Mancini IAD, Boeck T, Abinzano F, Mensinga F, Hauptstein J, Tessmar J, van Weeren PR , Malda J, Groll J, Levato R, Blunk T (2019)
EUREKA! Symposium, 9th and 10th October, 2019, Rudolf Virchow Center, (Würzburg, Germany)

2018

Schmidt S, Mancini IAD, Boeck T, Abinzano F, Mensinga A, Martini J, Tessmar J, van Weeren PR, Malda J, Groll J, Levato R, Blunk T (2018)
Chondrogenic Differentiation of Mesenchymal Stem Cells and Articular Cartilage Progenitor Cells in a 3D Printable Hyaluronic Acid Hydrogel
Annual Conference of the International Society for Biofabrication (ISBF), 28-31 October 2018 (Würzburg, Germany).

Leonard Forster, Julia Hauptstein, Ali Nadernezhad, Jürgen Groll, Torsten Blunk, Jörg Tessmar
Hyaluron-based dual-stage crosslinking approach for 3D bioprinting of mesenchymal stem cells
11TH WORLD BIOMATERIALS CONGRESS 11 – 15 December 2020
https://wbc2020.org/

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Leonard_Forster_Biomaterials_to_stimulate_stem_cells_WBC2020

Leonard Forster

Previous academic education: Bachelor Thesis – 2015; Master Thesis – 2017
Academic Advisor within SFB/TRR 225:  PD Dr. Jörg Teßmar
Location: University of Würzburg, Department for Functional Materials in Medicine and Dentistry
Topic of thesis: Hyaluronic acid based bioinks for bio-fabrication of mesenchymal stem cells
Main techniques and methodologies to be used: Synthesis, Gelation, Rheometry, 3D Bioprinting

Contact: leonard.forster@fmz.uni-wuerzburg.de

Stefanie Schmidt

Previous academic education: Biochemistry M. Sc.
Academic Advisor within SFB/TRR 225:  Prof. Dr. Torsten Blunk
Location: University Hospital Würzburg, Department of Trauma, Hand, Plastic and Reconstructive Surgery
Topic of thesis: Analysis of cell behavior in different 3D hydrogel models for chondrogenic differentiation.
Main techniques and methodologies to be used: 2D/3D Tissue Culture, Histology, IHC, Microscopy, qRT-PCR, quantitative DNA- and ECM-Assays, FACS, Western Blotting

Contact: Schmidt_S5@ukw.de

Julia Hauptstein

Previous academic education: Biochemistry M. Sc.
Academic Advisor within SFB/TRR 225:  Prof. Dr. Torsten Blunk
Location: University Hospital Würzburg, Department of Trauma, Hand, Plastic and Reconstructive Surgery
Topic of thesis: Hyaluronic Acid Hydrogels for Biofabrication to control Differentiation of Mesenchymal Stem Cells
Main techniques and methodologies to be used: 2D/3D Tissue Culture, Histology, IHC, Microscopy, qRT-PCR, quantitative DNA- and ECM-Assays, FACS, Western Blotting

Contact: Hauptstein_J@ukw.de

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