@article{PilusoHieblGorbetal.2011,
  author    = {Piluso, Susanna and Hiebl, Bernhard and Gorb, Stanislav N. and Kovalev, Alexander and Lendlein, Andreas and Neffe, Axel T.},
  title     = {Hyaluronic acid-based hydrogels crosslinked by copper-catalyzed azide-alkyne cycloaddition with tailorable mechanical properties},
  series = {The international journal of artificial organs},
  volume    = {34},
  journal   = {The international journal of artificial organs},
  number    = {2},
  publisher = {Wichtig},
  address   = {Milano},
  issn      = {0391-3988},
  doi       = {10.5301/IJAO.2011.6394},
  pages     = {192 -- 197},
  year      = {2011},
  abstract  = {Biopolymers of the extracellular matrix are attractive starting materials for providing degradable and biocompatible biomaterials. In this study, hyaluronic acid-based hydrogels with tunable mechanical properties were prepared by the use of copper-catalyzed azide-alkyne cycloaddition (known as "click chemistry"). Alkyne-functionalized hyaluronic acid was crosslinked with linkers having two terminal azide functionalities, varying crosslinker density as well as the lengths and rigidity of the linker molecules. By variation of the crosslinker density and crosslinker type, hydrogels with elastic moduli in the range of 0.5-4 kPa were prepared. The washed materials contained a maximum of 6.8 mg copper per kg dry weight and the eluate of the gel crosslinked with diazidostilbene did not show toxic effects on L929 cells. The hyaluronic acid-based hydrogels have potential as biomaterials for cell culture or soft tissue regeneration applications.},
  language  = {en}
}
@article{FedericoNoechelLoewenbergetal.2016,
  author    = {Federico, Stefania and N{\"o}chel, Ulrich and L{\"o}wenberg, Candy and Lendlein, Andreas and Neffe, Axel T.},
  title     = {Supramolecular hydrogel networks formed by molecular recognition of collagen and a peptide grafted to hyaluronic acid},
  series = {Acta biomaterialia},
  volume    = {38},
  journal   = {Acta biomaterialia},
  publisher = {Elsevier},
  address   = {Oxford},
  issn      = {1742-7061},
  doi       = {10.1016/j.actbio.2016.04.018},
  pages     = {1 -- 10},
  year      = {2016},
  abstract  = {The extracellular matrix (ECM) is a nano-structured, highly complex hydrogel, in which the macromolecules are organized primarily by non-covalent interactions. Here, in a biomimetic approach, the decorin-derived collagen-binding peptide LSELRLHNN was grafted to hyaluronic acid (HA) in order to enable the formation of a supramolecular hydrogel network together with collagen. The storage modulus of a mixture of collagen and HA was increased by more than one order of magnitude (G\&\#8242; = 157 Pa) in the presence of the HA-grafted peptide compared to a mixture of collagen and HA (G\&\#8242; = 6 Pa). The collagen fibril diameter was decreased, as quantified using electron microscopy, in the presence of the HA-grafted peptide. Here, the peptide mimicked the function of decorin by spatially organizing collagen. The advantage of this approach is that the non-covalent crosslinks between collagen molecules and the HA chains created by the peptide form a reversible and dynamic hydrogel, which could be employed for a diverse range of applications in regenerative medicine. Statement of Significance Biopolymers of the extracellular matrix (ECM) like collagen or hyaluronan are attractive starting materials for biomaterials. While in biomaterial science covalent crosslinking is often employed, in the native ECM, stabilization and macromolecular organization is primarily based on non-covalent interactions, which allows dynamic changes of the materials. Here, we show that collagen-binding peptides, derived from the small proteoglycan decorin, grafted to hyaluronic acid enable supramolecular stabilization of collagen hydrogels. These hydrogels have storage moduli more than one order of magnitude higher than mixtures of collagen and hyaluronic acid. Furthermore, the peptide supported the structural organization of collagen. Such hydrogels could be employed for a diverse range of applications in regenerative medicine. Furthermore, the rational design helps in the understanding ECM structuring.},
  language  = {en}
}