title: Self-assembled supramolecular polymers with tailorable properties that enhance cell attachment and proliferation.
abstract: Self-assembled supramolecular scaffolds, a combination of noncovalent interactions within a biocompatible polymer substrate, can be used for efficient construction of highly-controlled self-organizing hierarchical structures; these newly-developed biomaterials exhibit excellent mechanical properties, tunable surface hydrophilicity, low cytotoxicity and high biodegradability, making them highly attractive for tissue engineering and regenerative medicine applications. Herein, we demonstrate a novel supramolecular poly(ε-caprolactone) (PCL) containing self-complementary sextuple hydrogen-bonded uracil-diamidopyridine (U-DPy) moieties, which undergoes spontaneous self-assembly to form supramolecular polymer networks. Inclusion of various U-DPy contents enhanced the mechanical strength and viscosities of the resulting materials by up to two orders of magnitude compared to control PCL. Surface wettability and morphological studies confirmed physically-crosslinked films can be readily tailored to provide the desired surface properties. Cell viability assays indicated the excellent in vitro biocompatibility of U-DPy-functionalized substrates and indicate the potential of these materials for various biomedical applications. More importantly, mouse fibroblast NIH/3T3 cells cultured on these substrates displayed a more elongated cell morphology and had substantially higher cell densities than cells seeded on control PCL substrate, which indicates that introduction of U-DPy moieties into polymer matrixes could be used to create tissue culture surfaces that enhance cell attachment and proliferation. This new system is suggested as a potential route towards the practical realization of next-generation tissue-engineering scaffolds.
  
  
  
  In this study, we report a significant breakthrough in development of self-assembled supramolecular polymers to form well-defined scaffolds through self-complementary hydrogen-bonding interactions. These newly developed materials exhibited extremely good mechanical properties, fine-tunable hydrophilic characteristics and excellent biocompatibility due to hydrogen-bond-induced physical cross-linking. Importantly, cell adhesion and proliferation assays indicated that these substrates efficiently promoted the growth of mouse embryonic fibroblasts NIH/3T3 cells in vitro. Thus, this finding provides a simple and effective route for the development of next-generation tissue-engineering scaffolds that have improved mechanical properties, increased surface hydrophilicity and can enhance the growth and biological activity of adherent cells.
authors.affiliation: Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei 10607, Taiwan. Electronic address: cccheng@mail.ntust.edu.tw.
authors.forename: Chih-Chia
authors.initials: CC
authors.lastname: Cheng
authors.affiliation: Department of Chemical Engineering, National Taiwan University, Taipei 10617, Taiwan; Department of Chemical Engineering, National Taiwan University of Science and Technology, Taipei 10607, Taiwan; R&D Center for Membrane Technology, Chung Yuan Christian University, Chungli, Taoyuan 32043, Taiwan.
authors.forename: Duu-Jong
authors.initials: DJ
authors.lastname: Lee
authors.affiliation: Department of Materials Science and Engineering, National Taiwan University of Science and Technology, Taipei 10607, Taiwan.
authors.forename: Jem-Kun
authors.initials: JK
authors.lastname: Chen
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D003432:Cross-Linking Reagents / Q000737:chemistry; D005347:Fibroblasts / Q000166:cytology*; D006801:Humans; D006860:Hydrogen Bonding; D051379:Mice; D041681:NIH 3T3 Cells; D011091:Polyesters / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry; D012212:Rheology; D053838:Scattering, Small Angle; D014498:Uracil / Q000737:chemistry; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D003432:Cross-Linking Reagents; D011091:Polyesters; D011108:Polymers; D011725:Pyridines; D014867:Water; C016240:polycaprolactone; D014498:Uracil
keywords: Bioactive scaffolds; Multiple hydrogen bonds; Self-assembly; Supramolecular chemistry; Tissue engineering