title: Cell-instructive starPEG-heparin-collagen composite matrices.
abstract: Polymer hydrogels can be readily modulated with regard to their physical properties and functionalized to recapitulate molecular cues of the extracellular matrix (ECM). However, they remain structurally different from the hierarchical supramolecular assemblies of natural ECM. Accordingly, we herein report a set of hydrogel composite materials made from starPEG-peptide conjugates, maleimide-functionalized heparin and collagen type I that combine semisynthetic and ECM-derived components. Collagen fibrillogenesis was controlled by temperature and collagen concentration to form collagen microstructures which were then homogeneously distributed within the 3D composite matrix during hydrogel formation. The collagen-laden hydrogel materials showed a heterogeneous local variation of the stiffness and adhesion ligand density. Composite gels functionalized with growth factors and cell adhesive peptides (RGDSP) supported the growth of embedded human umbilical cord vein endothelial cells (HUVECs) and induced the alignment of embedded bone marrow-derived human mesenchymal stem cells (MSCs) to the collagen microstructures in vitro. The introduced composite hydrogel material is concluded to faithfully mimic cell-instructive features of the ECM.
  
  
  
  Cell-instructive materials play an important role in the generation of both regenerative therapies and advanced tissue and disease models. For that purpose, biofunctional polymer hydrogels recapitulating molecular cues of the extracellular matrix (ECM) were successfully applied in various different studies. However, hydrogels generally lack the hierarchical supramolecular structure of natural ECM. We have therefore developed a hydrogel composite material made from starPEG-peptide conjugates, maleimide-functionalized heparin and collagen type I fibrils. The collagen-laden scaffolds showed a heterogeneous local variation in the stiffness of the material. The composite gels were successfully tested in culture experiments with human umbilical cord vein endothelial cells and bone marrow-derived human mesenchymal stem cells. It was concluded that the composite scaffold was able to faithfully mimic important cell-instructive features of the ECM.
authors.affiliation: Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials, Budapester Strasse 27, Dresden, Saxony 01069, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Binner
authors.affiliation: Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials, Budapester Strasse 27, Dresden, Saxony 01069, Germany; School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, 2 George Street, Brisbane, Queensland 4000, Australia; Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, Queensland 4059, Australia.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Bray
authors.affiliation: Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials, Budapester Strasse 27, Dresden, Saxony 01069, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Friedrichs
authors.affiliation: Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials, Budapester Strasse 27, Dresden, Saxony 01069, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Freudenberg
authors.affiliation: Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials, Budapester Strasse 27, Dresden, Saxony 01069, Germany; Technische Universität Dresden, Center for Regenerative Therapies Dresden, Fetscherstrasse 105, Dresden, Saxony 01307, Germany.
authors.forename: Mikhail V
authors.initials: MV
authors.lastname: Tsurkan
authors.affiliation: Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials, Budapester Strasse 27, Dresden, Saxony 01069, Germany; Technische Universität Dresden, Center for Regenerative Therapies Dresden, Fetscherstrasse 105, Dresden, Saxony 01307, Germany. Electronic address: werner@ipfdd.de.
authors.forename: Carsten
authors.initials: C
authors.lastname: Werner
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry*; D002454:Cell Differentiation; D002470:Cell Survival; D024042:Collagen Type I / Q000737:chemistry*; D005109:Extracellular Matrix / Q000737:chemistry; D006493:Heparin / Q000737:chemistry*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D008422:Materials Testing; D059630:Mesenchymal Stem Cells / Q000166:cytology; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D024042:Collagen Type I; D020100:Hydrogels; D011092:Polyethylene Glycols; D006493:Heparin
keywords: Biohybrid composite; Bone marrow–derived human mesenchymal stem cells; Collagen type I; Human umbilical vein endothelial cells; Hydrogel