title: A modular and supramolecular approach to bioactive scaffolds for tissue engineering.
abstract: Bioactive polymeric scaffolds are a prerequisite for the ultimate formation of functional tissues. Here, we show that supramolecular polymers based on quadruple hydrogen bonding ureido-pyrimidinone (UPy) moieties are eminently suitable for producing such bioactive materials owing to their low-temperature processability, favourable degradation and biocompatible behaviour. Particularly, the reversible nature of the hydrogen bonds allows for a modular approach to gaining control over cellular behaviour and activity both in vitro and in vivo. Bioactive materials are obtained by simply mixing UPy-functionalized polymers with UPy-modified biomolecules. Low-molecular-weight bis-UPy-oligocaprolactones with cell adhesion promoting UPy-Gly-Arg-Gly-Asp-Ser (UPy-GRGDS) and the synergistic UPy-Pro-His-Ser-Arg-Asn (UPy-PHSRN) peptide sequences are synthesized and studied. The in vitro results indicate strong and specific cell binding of fibroblasts to the UPy-functionalized bioactive materials containing both UPy-peptides. An even more striking effect is seen in vivo where the formation of single giant cells at the interface between bioactive material and tissue is triggered.
authors.affiliation: Laboratory of Macromolecular and Organic Chemistry, Eindhoven University of Technology, PO Box 513, NL-5600 MB Eindhoven, The Netherlands.
authors.forename: Patricia Y W
authors.initials: PY
authors.lastname: Dankers
authors.forename: Martin C
authors.initials: MC
authors.lastname: Harmsen
authors.forename: Linda A
authors.initials: LA
authors.lastname: Brouwer
authors.forename: Marja J A
authors.initials: MJ
authors.lastname: van Luyn
authors.forename: E W
authors.initials: EW
authors.lastname: Meijer
mesh_terms: D016475:3T3 Cells; D000327:Adsorption; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D018929:Cell Culture Techniques / Q000379:methods*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D005353:Fibronectins / Q000737:chemistry / Q000494:pharmacology*; D046911:Macromolecular Substances / Q000737:chemistry; D008422:Materials Testing; D051379:Mice; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D011744:Pyrimidinones / Q000032:analysis / Q000737:chemistry*; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D001672:Biocompatible Materials; D005353:Fibronectins; D046911:Macromolecular Substances; D009842:Oligopeptides; D010446:Peptide Fragments; D011744:Pyrimidinones; C495978:prolyl-histidyl-seryl-arginyl-asparagine; C049554:glycyl-arginyl-glycyl-aspartyl-serine