Composite of Peptide-Supramolecular Polymer and Covalent Polymer Comprises a New Multifunctional, Bio-Inspired Soft Material.

Peptide-based supramolecular hydrogels are utilized as functional materials in tissue engineering, axonal regeneration, and controlled drug delivery. The Arg-Gly-Asp (RGD) ligand based supramolecular gels have immense potential in this respect, as this tripeptide is known to promote cell adhesion. Although several RGD-based supramolecular hydrogels have been reported, most of them are devoid of adequate resilience and long-range stability for in vitro cell culture. In a quest to improve the mechanical properties of these tripeptide-based gels and their durability in cell culture media, the Fmoc-RGD hydrogelator is non-covalently functionalized with a biocompatible and biodegradable polymer, chitosan, resulting in a composite hydrogel with enhanced gelation rate, mechanical properties and cell media durability. Interestingly, both Fmoc-RGD and Fmoc-RGD/chitosan composite hydrogels exhibit thixotropic properties. The utilization of the Fmoc-RGD/chitosan composite hydrogel as a scaffold for 2D and 3D cell cultures is demonstrated. The composite hydrogel is found to have notable antibacterial activity, which stems from the inherent antibacterial properties of chitosan. Furthermore, the composite hydrogels are able to produce ultra-small, mono-dispersed, silver nanoparticles (AgNPs) arranged on the fiber axis. Therefore, the authors' approach harnesses the attributes of both the supramolecular-polymer (Fmoc-RGD) and the covalent-polymer (chitosan) component, resulting in a composite hydrogel with excellent potential.

[1]  C. Giannini,et al.  Fmoc-FF and hexapeptide-based multicomponent hydrogels as scaffold materials. , 2019, Soft matter.

[2]  Malcolm K Horne,et al.  A Programmed Anti‐Inflammatory Nanoscaffold (PAIN) as a 3D Tool to Understand the Brain Injury Response , 2018, Advanced materials.

[3]  M. Guler,et al.  Tenascin-C derived signaling induces neuronal differentiation in a three-dimensional peptide nanofiber gel. , 2018, Biomaterials science.

[4]  Canelif Yilmaz,et al.  Promotion of neurite outgrowth by rationally designed NGF-β binding peptide nanofibers. , 2018, Biomaterials science.

[5]  J. Fei,et al.  A Photoinduced Reversible Phase Transition in a Dipeptide Supramolecular Assembly. , 2018, Angewandte Chemie.

[6]  F. Wang,et al.  Stoichiometry-Controlled Inversion of Supramolecular Chirality in Nanostructures Co-assembled with Bipyridines. , 2018, Chemistry.

[7]  A. Tekinay,et al.  Biocompatible Electroactive Tetra(aniline)-Conjugated Peptide Nanofibers for Neural Differentiation. , 2018, ACS applied materials & interfaces.

[8]  Anne Martel,et al.  Facile Control over the Supramolecular Ordering of Self-assembled Peptide Scaffolds by Simultaneous Assembly with a Polysacharride , 2017, Scientific Reports.

[9]  J. Mano,et al.  Nanoengineering Hybrid Supramolecular Multilayered Biomaterials Using Polysaccharides and Self‐Assembling Peptide Amphiphiles , 2017 .

[10]  Xiaocen Dou,et al.  Amino Acids and Peptide‐Based Supramolecular Hydrogels for Three‐Dimensional Cell Culture , 2017, Advanced materials.

[11]  R. Ulijn,et al.  Using experimental and computational energy equilibration to understand hierarchical self-assembly of Fmoc-dipeptide amphiphiles. , 2016, Soft matter.

[12]  A. Martel,et al.  Coassembled nanostructured bioscaffold reduces the expression of proinflammatory cytokines to induce apoptosis in epithelial cancer cells. , 2016, Nanomedicine : nanotechnology, biology, and medicine.

[13]  Samuel I. Stupp,et al.  Nucleation and Growth of Ordered Arrays of Silver Nanoparticles on Peptide Nanofibers: Hybrid Nanostructures with Antimicrobial Properties , 2016, Journal of the American Chemical Society.

[14]  Renliang Huang,et al.  Calcium-Ion-Triggered Co-assembly of Peptide and Polysaccharide into a Hybrid Hydrogel for Drug Delivery , 2016, Nanoscale Research Letters.

[15]  P. Bairi,et al.  Nanoengineering of a Supramolecular Gel by Copolymer Incorporation: Enhancement of Gelation Rate, Mechanical Property, Fluorescence, and Conductivity. , 2016, Langmuir : the ACS journal of surfaces and colloids.

[16]  L. Adler-Abramovich,et al.  Synergetic functional properties of two-component single amino acid-based hydrogels , 2015 .

[17]  Daniel J. Cornwell,et al.  Expanding the scope of gels – combining polymers with low-molecular-weight gelators to yield modified self-assembling smart materials with high-tech applications , 2015 .

[18]  P. Bairi,et al.  Integration of poly(ethylene glycol) in N-fluorenylmethoxycarbonyl-l-tryptophan hydrogel influencing mechanical, thixotropic, and release properties. , 2015, The journal of physical chemistry. B.

[19]  A. Tekinay,et al.  Self-assembled peptide amphiphile nanofibers and peg composite hydrogels as tunable ECM mimetic microenvironment. , 2015, Biomacromolecules.

[20]  David K. Smith,et al.  Multidomain hybrid hydrogels: spatially resolved photopatterned synthetic nanomaterials combining polymer and low-molecular-weight gelators. , 2014, Angewandte Chemie.

[21]  R. Ulijn,et al.  Design of nanostructures based on aromatic peptide amphiphiles. , 2014, Chemical Society reviews.

[22]  Ian W. Hamley,et al.  The bioactivity of composite Fmoc-RGDS-collagen gels. , 2014, Biomaterials science.

[23]  C. Feng,et al.  Convenient three-dimensional cell culture in supermolecular hydrogels. , 2014, ACS applied materials & interfaces.

[24]  Y. Duan,et al.  Chemistry, biology, and medicine of fluorescent nanomaterials and related systems: new insights into biosensing, bioimaging, genomics, diagnostics, and therapy. , 2014, Chemical reviews.

[25]  Ehud Gazit,et al.  Self-assembly of short peptides to form hydrogels: design of building blocks, physical properties and technological applications. , 2014, Acta biomaterialia.

[26]  Pier Paolo Pompa,et al.  Nanosilver-based antibacterial drugs and devices: mechanisms, methodological drawbacks, and guidelines. , 2014, Chemical Society reviews.

[27]  S. Stupp,et al.  Dynamic display of bioactivity through host-guest chemistry. , 2013, Angewandte Chemie.

[28]  Guren Zhang,et al.  Physicochemical properties and antioxidant activity of chitosan from the blowfly Chrysomya megacephala larvae. , 2013, International journal of biological macromolecules.

[29]  Charlotte A E Hauser,et al.  Tunable Mechanical Properties of Ultrasmall Peptide Hydrogels by Crosslinking and Functionalization to Achieve the 3D Distribution of Cells , 2013, Advanced healthcare materials.

[30]  Feihe Huang,et al.  Characterization of supramolecular gels. , 2013, Chemical Society reviews.

[31]  I. Hamley,et al.  Spectroscopic signatures of an Fmoc–tetrapeptide, Fmoc and fluorene , 2013 .

[32]  C. Jérôme,et al.  Chitosan-based biomaterials for tissue engineering , 2013 .

[33]  Di Zhang,et al.  Mechanical reinforcement of C2-phenyl-derived hydrogels for controlled cell adhesion , 2013 .

[34]  Sannakaisa Virtanen,et al.  Chemical and physical properties of regenerative medicine materials controlling stem cell fate , 2012, Annals of medicine.

[35]  Bappaditya Roy,et al.  Improved mechanical and photophysical properties of chitosan incorporated folic acid gel possessing the characteristics of dye and metal ion absorption , 2012 .

[36]  I. Hamley,et al.  Slow-release RGD-peptide hydrogel monoliths. , 2012, Langmuir : the ACS journal of surfaces and colloids.

[37]  X. Chen,et al.  Self-assembled polymeric nanoparticles based on oleic acid-grafted chitosan oligosaccharide: biocompatibility, protein adsorption and cellular uptake , 2012, Journal of Materials Science: Materials in Medicine.

[38]  Laura L Hyland,et al.  Viscoelastic properties and nanoscale structures of composite oligopeptide-polysaccharide hydrogels. , 2012, Biopolymers.

[39]  A. McNeil,et al.  Using polymeric additives to enhance molecular gelation: impact of poly(acrylic acid) on pyridine-based gelators , 2012 .

[40]  D. Adams,et al.  Correction: Fmoc-diphenylalanine hydrogels: understanding the variability in reported mechanical properties. , 2012, Soft matter.

[41]  Alberto Saiani,et al.  Effect of glycine substitution on Fmoc-diphenylalanine self-assembly and gelation properties. , 2011, Langmuir : the ACS journal of surfaces and colloids.

[42]  C. Alemán,et al.  Self-assembly of Fmoc-tetrapeptides based on the RGDS cell adhesion motif , 2011 .

[43]  F. Toma,et al.  Formation of efficient catalytic silver nanoparticles on carbon nanotubes by adenine functionalization. , 2011, Angewandte Chemie.

[44]  A. Banerjee,et al.  Amino acid based smart hydrogel: formation, characterization and fluorescence properties of silver nanoclusters within the hydrogel matrix , 2011 .

[45]  I. Hamley,et al.  Hydrogelation of self-assembling RGD-based peptides , 2011 .

[46]  B. Nilsson,et al.  Stabilizing self-assembled Fmoc-F5-Phe hydrogels by co-assembly with PEG-functionalized monomers. , 2011, Chemical communications.

[47]  Tal Dvir,et al.  Nanotechnological strategies for engineering complex tissues. , 2020, Nature nanotechnology.

[48]  A. Banerjee,et al.  Short-peptide-based hydrogel: a template for the in situ synthesis of fluorescent silver nanoclusters by using sunlight. , 2010, Chemistry.

[49]  Ming Kong,et al.  Antimicrobial properties of chitosan and mode of action: a state of the art review. , 2010, International journal of food microbiology.

[50]  Kyle L. Morris,et al.  Low molecular weight gelator-dextran composites. , 2010, Chemical communications.

[51]  S. Shinkai,et al.  Regulation of a real-time self-healing process in organogel tissues by molecular adhesives. , 2010, Angewandte Chemie.

[52]  D. Pochan,et al.  Rheological properties of peptide-based hydrogels for biomedical and other applications. , 2010, Chemical Society reviews.

[53]  P. Topham,et al.  Peptide conjugate hydrogelators , 2010 .

[54]  W. Frith,et al.  Relationship between molecular structure, gelation behaviour and gel properties of Fmoc-dipeptides , 2010 .

[55]  E. Kumacheva,et al.  Properties and emerging applications of self-assembled structures made from inorganic nanoparticles. , 2010, Nature nanotechnology.

[56]  D. Seliktar,et al.  Self-assembled Fmoc-peptides as a platform for the formation of nanostructures and hydrogels. , 2009, Biomacromolecules.

[57]  Mi Zhou,et al.  Self-assembled peptide-based hydrogels as scaffolds for anchorage-dependent cells. , 2009, Biomaterials.

[58]  Paul Sanderson,et al.  A new method for maintaining homogeneity during liquid–hydrogel transitions using low molecular weight hydrogelators , 2009 .

[59]  Glyn L. Devlin,et al.  Functionalised amyloid fibrils for roles in cell adhesion. , 2008, Biomaterials.

[60]  B. Geiger,et al.  Supramolecular crafting of cell adhesion. , 2007, Biomaterials.

[61]  Tao Wang,et al.  Chitosan nanoparticle as protein delivery carrier--systematic examination of fabrication conditions for efficient loading and release. , 2007, Colloids and surfaces. B, Biointerfaces.

[62]  Zhirong Zhang,et al.  Evaluation and modification of N-trimethyl chitosan chloride nanoparticles as protein carriers. , 2007, International journal of pharmaceutics.

[63]  H. Frey,et al.  Water‐Soluble Fluorescent Ag Nanoclusters Obtained from Multiarm Star Poly(acrylic acid) as “Molecular Hydrogel” Templates , 2007 .

[64]  Michael S. Goldberg,et al.  Nanostructured materials for applications in drug delivery and tissue engineering , 2007, Journal of biomaterials science. Polymer edition.

[65]  Samuel I Stupp,et al.  Heparin binding nanostructures to promote growth of blood vessels. , 2006, Nano letters.

[66]  Meital Reches,et al.  Rigid, Self‐Assembled Hydrogel Composed of a Modified Aromatic Dipeptide , 2006 .

[67]  Samuel I Stupp,et al.  Presentation of RGDS epitopes on self-assembled nanofibers of branched peptide amphiphiles. , 2006, Biomacromolecules.

[68]  A. Miller,et al.  Nanostructured Hydrogels for Three‐Dimensional Cell Culture Through Self‐Assembly of Fluorenylmethoxycarbonyl–Dipeptides , 2006 .

[69]  P. Janmey,et al.  Tissue Cells Feel and Respond to the Stiffness of Their Substrate , 2005, Science.

[70]  Darrin J. Pochan,et al.  Cytocompatibility of self-assembled β-hairpin peptide hydrogel surfaces , 2005 .

[71]  Samuel I Stupp,et al.  Self-assembling peptide amphiphile nanofiber matrices for cell entrapment. , 2005, Acta biomaterialia.

[72]  J. Hubbell,et al.  Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering , 2005, Nature Biotechnology.

[73]  Krista L. Niece,et al.  Selective Differentiation of Neural Progenitor Cells by High-Epitope Density Nanofibers , 2004, Science.

[74]  Horst Kessler,et al.  RGD modified polymers: biomaterials for stimulated cell adhesion and beyond. , 2003, Biomaterials.

[75]  Shuguang Zhang Fabrication of novel biomaterials through molecular self-assembly , 2003, Nature Biotechnology.

[76]  A. J. Grodzinsky,et al.  Self-assembling peptide hydrogel fosters chondrocyte extracellular matrix production and cell division: Implications for cartilage tissue repair , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[77]  Samuel I Stupp,et al.  Peptide-amphiphile nanofibers: A versatile scaffold for the preparation of self-assembling materials , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[78]  J. Hubbell,et al.  Incorporation of adhesion peptides into nonadhesive hydrogels useful for tissue resurfacing. , 1998, Journal of biomedical materials research.

[79]  A. Rich,et al.  Self-complementary oligopeptide matrices support mammalian cell attachment. , 1995, Biomaterials.

[80]  Erkki Ruoslahti,et al.  Cell attachment activity of fibronectin can be duplicated by small synthetic fragments of the molecule , 1984, Nature.