Hierarchical Systems

In their natural environment, cells are surrounded by a matrix that enables their survival and determines their adhesion, growth, proliferation, migration, differentiation and function. Therefore, soluble factors that are reversible immobilized in the so called extracellular matrix (ECM) as well as specifically acting binding moieties are of utmost importance. Main components of the ECM are hydrogels and insoluble protein fibres that serve as mechanical scaffold for the cells. Another important structural element are basal membranes, ultrathin separation layers between tissues.

A core activity at FMZ is the preparation and evaluation of biodegradable materials and structures that mimic the ECM as closely as possible in its morphology, biochemical function and hierarchical composition. Modified biopolymers as well as biocompatible functional polymers are used as components for coatings, hydrogels and nanofibrous constructs to achieve this goal. For the generation of hierarchy, methods such as electrospinning and rapid-prototyping techniques are applied.
ECM

Another focus area of research are injectable systems for in-situ Tissue Engineering. For this, biocompatible cross-linking chemistries are essential that do not negatively affect cell viability. Examples for this are Michael-Addition or click-chemistry. Finally, the rheological properties of these systems have to be controlled properly.

Cryostructuring
Solution Electrospinning
Materials for specific Approaches

Cryostructuring

Many types of human tissues show a hierarchical structure in their chemical and structural composition. One possibility to generate scaffolds with aligned and continuous micropores is the directional freezing. Precursor solutions, suspensions, or dispersions are frozen in the presence of an external temperature gradient. The ice crystal growth thus occurs in the opposite direction to the heat flow. After lyophilization, a porous scaffold that mimics the structure and the chemical composition of the extracellular matrix of native tissue can be obtained.

 

Contact:
Prof. Dr. rer. nat. Jürgen Groll
Telephone +49(0)931 201-73610
fmz-office@uni-wuerzburg.de

Solution Electrospinning

Solution electrospinning has been a paramount technique in fabricating fibrous scaffolds that mimic the natural 3-dimensional ECM architecture. In the fabrication of fibrous meshes, we use combination of different biocompatible synthetic and natural polymers. Resulting fibers can be investigated in three fundamental directions with respect to cell-scaffold interactions: Matrix elasticity, topographical features and bioactive cues.

Here, in FMZ, we fabricate nano/micro-sized polymer fibers with an engineered surface that can facilitate various functionality for desired biological applications. The main focus of our research, but not limited to, is specific surface activation of fibers that inhibits unspecific protein adsorption while providing a controllable bioactive interface for the manipulation of cellular processes such as adhesion, proliferation, migration and differentiation.

Contact:
Prof. Dr. rer. nat. Jürgen Groll
Telephone +49(0)931 201-73610
fmz-office@uni-wuerzburg.de

Materials for Specific Approaches

Besides the elsewhere described material for nanoparticles or bioinks we also apply our synthetic know-how for the development of polymers for many different other biomedical approaches.

Specifically terminated polyoxazolines are for example studied to allow chemo-selective immobilization of sugars and peptides to one polymer chain and thereby study specific ligand interaction with cells. Other approaches make use of the defined chemistry of polyoxazolines and polyglycidols to allow side chain immobilization of proteins and peptides or the attachement of side functions, which can be used as tissue adhesives for cartilage repair.

Other applications of functionalized polymers are surface coatings of electrospun polymer fibres for improved biocompatibility and cell adhesion or the formation of hydrogels for specific imaging applications, like the study of trypanosomes in collaboration with the department of zoology.

Contact:
Prof. Dr. rer. nat. Jürgen Groll
Telephone +49(0)931 201-73610
fmz-office@uni-wuerzburg.de

Dr. habil Jörg Tessmar
Telephone +49(0)931 201-73720
joerg.tessmar@uni-wuerzburg.de

Prof. Dr. rer. nat. Jürgen Groll
Telephone +49(0)931 201-73610
fmz-office@uni-wuerzburg.de

Dr. rer. nat. Jörg Teßmar
Telephone +49(0)931 201-73720
joerg.tessmar@uni-wuerzburg.de

K Stuckensen , A Schwab, M Knauer, E Muiños-López, F Ehlicke, J Reboredo, F Granero-Moltó, U Gbureck, F Prósper, H Walles, J Groll, Tissue Mimicry in Morphology and Composition Promotes Hierarchical Matrix Remodeling of Invading Stem Cells in Osteochondral and Meniscus Scaffolds. Advanced Materials, 2018. 30(28)

M Rödel, K Baumann, J Groll, U Gbureck, Simultaneous structuring and mineralization of silk fibroin scaffolds. Journal of Tissue Engineering, 2018. 9

L Wistlich, J Kums, A Rossi, KH Heffels, H Wajant, J Groll. Multimodal Bioactivation of Hydrophilic Electrospun Nanofibers Enables Simultaneous Tuning of Cell Adhesivity and Immunomodulatory Effects, Advanced Functional Materials, 27, Issue46, December 8, 2017, 1702903

A Rossi, L Wistlich, KH Heffels, H Walles, J Groll. Isotropic Versus Bipolar Functionalized Biomimetic Artificial Basement Membranes and Their Evaluation in Long‐Term Human Cell Co‐Culture,Volume5,  Advanced Functional Materials  Issue15, August 10, 2016, 1939-1948

S. Stichler, T. Jüngst, M. Schamel, I. Zilkowski, M. Kuhlmann, T. Böck, T. Blunk, J. Teßmar, J. Groll. Thiol-ene Clickable Poly(glycidol) Hydrogels for Biofabrication. Annals of Biomedical Engineering 2016

T. Jüngst, W. Smolan, K. Schacht, T. Scheibel, J. Groll. Strategies and Molecular Design Criteria for 3D Printable Hydrogels. Chemical Reviews 2016

M. Kessler, J. Groll, J. Tessmar. Application of Linear and Branched Poly(Ethylene Glycol)-Poly(Lactide) Block Copolymers for the Preparation of Films and Solution Electrospun Meshes. Macromolecular Bioscience 2015

M. Schmitz, M. Kuhlmann, O. Reimann, C.P.R. Hackenberger, J. Groll. Side Chain Cysteine Functionalized Poly(2-oxazoline)s for Multiple Peptide Conjugation by Native Chemical Ligation. Biomacromolecules 2015

K. Stuckensen, A. Ewald, J. Groll, U. Gbureck. In situ formation of multilayer biocomposite with anisotropic crystal orientation. Materials Letters 2014; 120(1): 111-114.

M Bartneck, KH Heffels, Y Pan, M Bovi, G Zwadlo-Klarwasser, J Groll. Inducing healing-like human primary macrophage phenotypes by 3D hydrogel coated nanofibres Biomaterials Volume 33, Issue 16, June 2012, Pages 4136-4146

D. Grafahrend, K.-H. Heffels, M.V. Beer, P. Gasteier, M. Moeller, G. Boehm, P.D. Dalton, J. Groll: Degradable polyester scaffolds with controlled surface chemistry combining minimal protein adsorption with specific bioactivation. Nature Materials 2011, 10, 67-73.