25th Anniversary Article: Supramolecular Materials for Regenerative Medicine

In supramolecular materials, molecular building blocks are designed to interact with one another via non-covalent interactions in order to create function. This offers the opportunity to create structures similar to those found in living systems that combine order and dynamics through the reversibility of intermolecular bonds. For regenerative medicine there is a great need to develop materials that signal cells effectively, deliver or bind bioactive agents in vivo at controlled rates, have highly tunable mechanical properties, but at the same time, can biodegrade safely and rapidly after fulfilling their function. These requirements make supramolecular materials a great platform to develop regenerative therapies. This review illustrates the emerging science of these materials and their use in a number of applications for regenerative medicine.

[1]  S. Stupp,et al.  Supramolecular Materials: Self-Organized Nanostructures , 1997, Science.

[2]  E. Thomas,et al.  Supramolecular Routes to Hierarchical Structures: Comb-Coil Diblock Copolymers Organized with Two Length Scales , 1999 .

[3]  S. Voss,et al.  Skin Regeneration in Adult Axolotls: A Blueprint for Scar-Free Healing in Vertebrates , 2012, PloS one.

[4]  H. Schneider Applications of Supramolecular Chemistry , 2012 .

[5]  C. Mao,et al.  Hierarchical self-assembly of DNA into symmetric supramolecular polyhedra , 2008, Nature.

[6]  Shuguang Zhang,et al.  In vivo studies on angiogenic activity of two designer self-assembling peptide scaffold hydrogels in the chicken embryo chorioallantoic membrane. , 2012, Nanoscale.

[7]  S. Stupp,et al.  Biological synthesis of tooth enamel instructed by an artificial matrix. , 2010, Biomaterials.

[8]  O. Ikkala,et al.  Supramolecular polymeric materials with hierarchical structure-within-structure morphologies , 1999 .

[9]  Hisatoshi Kobayashi,et al.  Design of Tissue-engineered Nanoscaffold Through Self-assembly of Peptide Amphiphile , 2006 .

[10]  C. Chung,et al.  Osteoblastic differentiation of human bone marrow stromal cells in self-assembled BMP-2 receptor-binding peptide-amphiphiles. , 2009, Biomaterials.

[11]  C. P. Kaushik,et al.  Gamma Radiation‐Induced Changes in Trombay Nuclear Waste Glass Containing Iron , 2013 .

[12]  Alberto Paleari,et al.  Glycine-Spacers Influence Functional Motifs Exposure and Self-Assembling Propensity of Functionalized Substrates Tailored for Neural Stem Cell Cultures , 2009, Front. Neuroeng..

[13]  Richard A. L. Jones Challenges in soft nanotechnology. , 2009, Faraday discussions.

[14]  Elly M. Tanaka,et al.  Cells keep a memory of their tissue origin during axolotl limb regeneration , 2009, Nature.

[15]  R. Shah,et al.  Supramolecular design of self-assembling nanofibers for cartilage regeneration , 2010, Proceedings of the National Academy of Sciences of the United States of America.

[16]  Job Boekhoven,et al.  Dissipative self-assembly of a molecular gelator by using a chemical fuel. , 2010, Angewandte Chemie.

[17]  Samuel I Stupp,et al.  Development of bioactive peptide amphiphiles for therapeutic cell delivery. , 2010, Acta biomaterialia.

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

[19]  R. Bitton,et al.  Electrostatic control of bioactivity. , 2011, Angewandte Chemie.

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

[21]  P. R. Hania,et al.  Light-driven dynamic pattern formation. , 2005, Angewandte Chemie.

[22]  Ronald T Raines,et al.  Collagen structure and stability. , 2009, Annual review of biochemistry.

[23]  Y. Lee,et al.  Simultaneous microfabrication and tuning of the permselective properties in microporous polymers using X-ray lithography. , 2013, Small.

[24]  S. Whitelam,et al.  Do hierarchical structures assemble best via hierarchical pathways , 2012, 1211.3763.

[25]  M. Nimni Polypeptide growth factors: targeted delivery systems. , 1997, Biomaterials.

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

[27]  E. W. Meijer,et al.  Functional Supramolecular Polymers , 2012, Science.

[28]  B. Guillotin,et al.  Differentiation of pre-osteoblast cells on poly(ethylene terephthalate) grafted with RGD and/or BMPs mimetic peptides. , 2010, Biomaterials.

[29]  M. Klagsbrun Mediators of angiogenesis: the biological significance of basic fibroblast growth factor (bFGF)-heparin and heparan sulfate interactions. , 1992, Seminars in cancer biology.

[30]  D. Sorriento,et al.  Targeting angiogenesis: structural characterization and biological properties of a de novo engineered VEGF mimicking peptide. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[31]  J. Vacanti,et al.  Tissue engineering : Frontiers in biotechnology , 1993 .

[32]  Richard T. Lee,et al.  Local myocardial insulin-like growth factor 1 (IGF-1) delivery with biotinylated peptide nanofibers improves cell therapy for myocardial infarction. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[33]  Seung Jin Lee,et al.  The effect of spacer arm length of an adhesion ligand coupled to an alginate gel on the control of fibroblast phenotype. , 2010, Biomaterials.

[34]  M. Alini,et al.  Differential response of human bone marrow stromal cells to either TGF-β1 or rhGDF-5 , 2011, European Spine Journal.

[35]  T. Fukushima,et al.  Molecular engineering of coaxial donor-acceptor heterojunction by coassembly of two different hexabenzocoronenes: graphitic nanotubes with enhanced photoconducting properties. , 2007, Journal of the American Chemical Society.

[36]  Taekjip Ha,et al.  Defining Single Molecular Forces Required to Activate Integrin and Notch Signaling , 2013, Science.

[37]  Yoshinori Kuboki,et al.  Type I collagen‐induced osteoblastic differentiation of bone‐marrow cells mediated by collagen‐α2β1 integrin interaction , 2000 .

[38]  C. Tabin,et al.  Limb regeneration revisited , 2009, Journal of biology.

[39]  Samuel I. Stupp,et al.  A Self-Assembly Pathway to Aligned Monodomain Gels , 2010, Nature materials.

[40]  Karl Fischer,et al.  Temperature triggered self-assembly of polypeptides into multivalent spherical micelles. , 2008, Journal of the American Chemical Society.

[41]  Samuel I Stupp,et al.  Molecular simulation study of peptide amphiphile self-assembly. , 2008, The journal of physical chemistry. B.

[42]  Owen R. Lozman,et al.  Discotic liquid crystals 25 years on , 2002 .

[43]  R. Lieber SKELETAL MUSCLE ADAPTABILITY. I: REVIEW OF BASIC PROPERTIES , 1986, Developmental medicine and child neurology.

[44]  J. de Boer,et al.  A supramolecular system for the electrochemically controlled release of cells. , 2012, Angewandte Chemie.

[45]  C. Murphy,et al.  Hydrogels with well-defined peptide-hydrogel spacing and concentration: impact on epithelial cell behavior(). , 2012, Soft matter.

[46]  Hisatoshi Kobayashi,et al.  Osteogenic differentiation of mesenchymal stem cells in self-assembled peptide-amphiphile nanofibers. , 2006, Biomaterials.

[47]  Ben L Feringa,et al.  Reversible Optical Transcription of Supramolecular Chirality into Molecular Chirality , 2004, Science.

[48]  Samuel I Stupp,et al.  Photodynamic control of bioactivity in a nanofiber matrix. , 2012, ACS nano.

[49]  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.

[50]  S. Sen,et al.  Matrix Elasticity Directs Stem Cell Lineage Specification , 2006, Cell.

[51]  A Ratcliffe,et al.  Cartilage and diarthrodial joints as paradigms for hierarchical materials and structures. , 1992, Biomaterials.

[52]  A. Grodzinsky,et al.  Controlled delivery of transforming growth factor β1 by self-assembling peptide hydrogels induces chondrogenesis of bone marrow stromal cells and modulates Smad2/3 signaling. , 2011, Tissue engineering. Part A.

[53]  Michael G. Fehlings,et al.  Self-Assembling Nanofibers Inhibit Glial Scar Formation and Promote Axon Elongation after Spinal Cord Injury , 2008, The Journal of Neuroscience.

[54]  Makinen,et al.  Switching supramolecular polymeric materials with multiple length scales , 1998, Science.

[55]  R. Gamelli,et al.  Heparin and heparan sulphate protect basic fibroblast growth factor from non-enzymic glycosylation. , 1999, The Biochemical journal.

[56]  A. Cardin,et al.  Molecular Modeling of Protein‐Glycosaminoglycan Interactions , 1989, Arteriosclerosis.

[57]  Samuel I Stupp,et al.  Synthesis, self-assembly, and characterization of supramolecular polymers from electroactive dendron rodcoil molecules. , 2004, Journal of the American Chemical Society.

[58]  H. Kleinman,et al.  A synthetic peptide containing the IKVAV sequence from the A chain of laminin mediates cell attachment, migration, and neurite outgrowth. , 1989, The Journal of biological chemistry.

[59]  P. Cullis,et al.  Drug Delivery Systems: Entering the Mainstream , 2004, Science.

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

[61]  Mahidhar M. Durbhakula,et al.  Chondrogenic potential of progenitor cells derived from human bone marrow and adipose tissue: A patient‐matched comparison , 2005, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[62]  G. Sena,et al.  Built to rebuild: in search of organizing principles in plant regeneration. , 2010, Current opinion in genetics & development.

[63]  Pere Roca-Cusachs,et al.  Finding the weakest link – exploring integrin-mediated mechanical molecular pathways , 2012, Journal of Cell Science.

[64]  Fabrizio Gelain,et al.  Designer Self-Assembling Peptide Nanofiber Scaffolds for Adult Mouse Neural Stem Cell 3-Dimensional Cultures , 2006, PloS one.

[65]  F. Barry,et al.  Chondrogenic differentiation of mesenchymal stem cells from bone marrow: differentiation-dependent gene expression of matrix components. , 2001, Experimental cell research.

[66]  G. Whitesides,et al.  Noncovalent Synthesis: Using Physical-Organic Chemistry To Make Aggregates , 1995 .

[67]  S. Stupp,et al.  Self‐assembling peptide amphiphile promotes plasticity of serotonergic fibers following spinal cord injury , 2010, Journal of neuroscience research.

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

[69]  S. Odelberg,et al.  A transitional extracellular matrix instructs cell behavior during muscle regeneration. , 2010, Developmental biology.

[70]  Michael O'Keeffe,et al.  Systematic Design of Pore Size and Functionality in Isoreticular MOFs and Their Application in Methane Storage , 2002, Science.

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

[72]  Alexander Sasha Rabchevsky,et al.  Therapeutic interventions following mammalian spinal cord injury. , 2001, Archives of neurology.

[73]  S. Stupp,et al.  The role of bioactive nanofibers in enamel regeneration mediated through integrin signals acting upon C/EBPα and c-Jun. , 2013, Biomaterials.

[74]  A. N. Semenov,et al.  Hierarchical self-assembly of chiral rod-like molecules as a model for peptide β-sheet tapes, ribbons, fibrils, and fibers , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[75]  Andrew M. Smith,et al.  Designing peptide based nanomaterials. , 2008, Chemical Society reviews.

[76]  Shuguang Zhang,et al.  Designer functionalized self-assembling peptide nanofiber scaffolds for growth, migration, and tubulogenesis of human umbilical vein endothelial cells , 2008 .

[77]  B. Ninham,et al.  Theory of self-assembly of hydrocarbon amphiphiles into micelles and bilayers , 1976 .

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

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

[80]  R. Langer,et al.  Drug delivery and targeting. , 1998, Nature.

[81]  A. Javed,et al.  Osteogenic differentiation of human mesenchymal stem cells synergistically enhanced by biomimetic peptide amphiphiles combined with conditioned medium. , 2011, Acta biomaterialia.

[82]  Steve Weiner,et al.  THE MATERIAL BONE: Structure-Mechanical Function Relations , 1998 .

[83]  Stephen Marshall,et al.  Biocatalytic induction of supramolecular order , 2010, Nature Chemistry.

[84]  R. Nolte,et al.  Synthesis and hierarchical self-assembly of cavity-containing facial amphiphiles. , 2003, The Journal of organic chemistry.

[85]  George M. Whitesides,et al.  Using Mixed Self-Assembled Monolayers Presenting RGD and (EG)3OH Groups To Characterize Long-Term Attachment of Bovine Capillary Endothelial Cells to Surfaces , 1998 .

[86]  Yasuhiko Tabata,et al.  Tissue regeneration based on growth factor release. , 2003, Tissue engineering.

[87]  G. Whitesides,et al.  Self-Assembly at All Scales , 2002, Science.

[88]  E. W. Meijer,et al.  A modular and supramolecular approach to bioactive scaffolds for tissue engineering , 2005, Nature materials.

[89]  K. Chien,et al.  Regenerative medicine and human models of human disease , 2008, Nature.

[90]  Sabrina Pricl,et al.  Self-assembled multivalent RGD-peptide arrays--morphological control and integrin binding. , 2013, Organic & biomolecular chemistry.

[91]  Omar K Farha,et al.  Metal-organic framework materials as catalysts. , 2009, Chemical Society reviews.

[92]  S. Stupp,et al.  Spontaneous and X-ray–Triggered Crystallization at Long Range in Self-Assembling Filament Networks , 2010, Science.

[93]  C James Kirkpatrick,et al.  Dynamic in vivo biocompatibility of angiogenic peptide amphiphile nanofibers. , 2009, Biomaterials.

[94]  G. Colombo,et al.  Structural determinants of the unusual helix stability of a de novo engineered vascular endothelial growth factor (VEGF) mimicking peptide. , 2008, Chemistry.

[95]  S. Bryant,et al.  Vertebrate limb regeneration and the origin of limb stem cells. , 2002, The International journal of developmental biology.

[96]  Samuel I. Stupp,et al.  Physical properties of hierarchically ordered self-assembled planar and spherical membranes , 2010 .

[97]  Milan Mrksich,et al.  Using self-assembled monolayers to model the extracellular matrix. , 2009, Acta biomaterialia.

[98]  D. Grainger,et al.  Modulating fibroblast adhesion, spreading, and proliferation using self-assembled monolayer films of alkylthiolates on gold. , 2000, Journal of biomedical materials research.

[99]  S. Stupp,et al.  Tuning supramolecular mechanics to guide neuron development. , 2013, Biomaterials.

[100]  Samuel I Stupp,et al.  Tubular hydrogels of circumferentially aligned nanofibers to encapsulate and orient vascular cells. , 2012, Biomaterials.

[101]  F. Bates,et al.  Synthesis and self-assembly of RGD-functionalized PEO-PB amphiphiles. , 2009, Biomacromolecules.

[102]  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.

[103]  M. Distefano,et al.  Micropatterning gradients and controlling surface densities of photoactivatable biomolecules on self-assembled monolayers of oligo(ethylene glycol) alkanethiolates. , 1997, Chemistry & biology.

[104]  S. Stupp Self-assembly of rodcoil molecules , 1998 .

[105]  D. Stocum The urodele limb regeneration blastema. Determination and organization of the morphogenetic field. , 1984, Differentiation; research in biological diversity.

[106]  Robert M. Nerem,et al.  Dynamic Mechanical Conditioning of Collagen-Gel Blood Vessel Constructs Induces Remodeling In Vitro , 2000, Annals of Biomedical Engineering.

[107]  Yoshihisa Suzuki,et al.  Accelerated bone repair with the use of a synthetic BMP-2-derived peptide and bone-marrow stromal cells. , 2005, Journal of biomedical materials research. Part A.

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

[109]  H. Mihara,et al.  Soft materials based on designed self-assembling peptides: from design to application. , 2013, Molecular bioSystems.

[110]  K. Koishi,et al.  The transforming growth factor-betas: multifaceted regulators of the development and maintenance of skeletal muscles, motoneurons and Schwann cells. , 2002, The International journal of developmental biology.

[111]  R. Lakes Materials with structural hierarchy , 1993, Nature.

[112]  B. Feringa,et al.  New Functional Materials Based on Self‐Assembling Organogels: From Serendipity towards Design , 2000 .

[113]  A. Mata,et al.  Self-Assembly of Large and Small Molecules into Hierarchically Ordered Sacs and Membranes , 2008, Science.

[114]  George M. Whitesides,et al.  Dynamic self-assembly of magnetized, millimetre-sized objects rotating at a liquid–air interface , 2000, Nature.

[115]  Stuart L James,et al.  Metal-organic frameworks. , 2003, Chemical Society reviews.

[116]  L. V. Williams,et al.  Tissue repair and the dynamics of the extracellular matrix. , 2004, The international journal of biochemistry & cell biology.

[117]  Bartosz A Grzybowski,et al.  Principles and implementations of dissipative (dynamic) self-assembly. , 2006, The journal of physical chemistry. B.

[118]  S. Stupp,et al.  Encapsulation of pyrene within self-assembled peptide amphiphile nanofibers , 2005 .