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

Prof. Dr. Torsten Blunk

University Hospital Würzburg, Department of Trauma, Hand, Plastic and Reconstructive Surgery
Contact: Blunk_T@ukw.de

Scientific Leadership: Boards, Committees

Dr. habil Jörg Tessmar

University Hospital Würzburg, Department for Functional Materials in Medicine and Dentistry
Contact: joerg.tessmar@uni-wuerzburg.de

Scientific Leadership: Boards, Committees

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

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)

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)

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 https://www.biofabrication2022.org/ 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 https://www.biofabrication2022.org/   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