Production of heparin-functionalized hydrogels for the development of responsive and controlled growth factor delivery systems.

Methods to assemble polymeric hydrogels on the basis of noncovalent protein-glycosaminoglycan interactions have been previously demonstrated by us and others and hold promise in the development of receptor-responsive hydrogel materials; improvements in the mechanical properties of such systems would broaden their utility. Thus, in situ crosslinkable and degradable heparin-containing hydrogels were designed for the binding and controlled release of growth factors. Specifically, maleimide-functionalized high molecular weight heparin (HMWH) was synthesized via straightforward chemical methods that permitted facile and controllable modification of carboxylates in HMWH with maleimide groups via control of catalyst and reaction conditions, as assessed via 1H NMR spectroscopy.

Functionalizing electrospun fibers with biologically relevant macromolecules.

The development of functionalized polymers that can elicit specific biological responses is of great interest in the biomedical community, as well as the development of methods to fabricate these biologically functionalized polymers. For example, the generation of fibrous matrices with biological properties and fiber diameters commensurate with those of the natural extracellular matrix (ECM) may permit the development of novel materials for use in wound healing or tissue engineering. The goal of this work is, therefore, to create a biologically active functionalized electrospun matrix to permit immobilization and long-term delivery of growth factors.

Rheological characterization of polysaccharide-poly(ethylene glycol) star copolymer hydrogels.

Binding interactions between low molecular weight heparin (LMWH) and heparin-binding peptides (HBP) have been applied as a strategy for the assembly of hydrogels that are capable of sequestering growth factors and delivering them in a controlled manner. In this work, the assembly of four-arm star poly(ethylene glycol) (PEG)-LMWH conjugate with PEG-HBP conjugates has been investigated. The interactions between LMWH and the heparin-binding regions of antithrombin III (ATIII) or the heparin interacting protein (HIP) have been characterized via heparin affinity chromatography and surface plasmon resonance (SPR); results indicate that the two peptides have slightly different affinities for heparin and LMWH, and bind LMWH with micromolar affinity.

Polysaccharide-poly(ethylene glycol) star copolymer as a scaffold for the production of bioactive hydrogels.

The production of polysaccharide-derivatized surfaces, polymers, and biomaterials has been shown to be a useful strategy for mediating the biological properties of materials, owing to the importance of polysaccharides for the sequestration and protection of bioactive proteins in vivo. We have therefore sought to combine the benefits of polysaccharide derivatization of polymers with unique opportunities to use these polymers for the production of bioactive, noncovalently assembled hydrogels. Accordingly, we report the synthesis of a heparin-modified poly(ethylene glycol) (PEG) star copolymer that can be used in the assembly of bioactive hydrogel networks via multiple strategies and that is also competent for the delivery of bioactive growth factors.

Spontaneous formation of an exfoliated polystyrene-clay nanocomposite using a star-shaped polymer.

Mixtures of five-arm star polystyrene with an organoclay spontaneously formed exfoliated nanocomposites when annealed, validating a recent theoretical prediction by Singh and Balazs (Polym. Int. 2000, 49, 469.

Supramolecular pseudorotaxane polymers from complementary pairs of homoditopic molecules.

Self-assembly of supramolecular pseudorotaxane polymers from complementary homoditopic building blocks comprised of bis(dibenzo-24-crown-8) esters derived from the hydroxymethyl crown ether and aliphatic diacid chlorides (CxC, x = number of methylene units in the diacid segment) and 1,10-bis[p-(benzylammoniomethyl)phenoxy]alkane bis(hexafluorophosphate)s (AyA, y = number of methylene units in the linker) has been studied. (1)H NMR spectroscopic studies of bis[(2-dibenzo-24-crown-8)methyl] sebacate (C8C) with dibenzylammonium hexafluorophosphate (6) showed that the two binding sites of the ditopic host are equivalent and independent (no positive or negative cooperativity). Likewise the binding sites in 1,10-bis[p-(benzylammoniomethyl)phenoxy]decane bis(hexafluorophosphate) (A10A) were shown to behave independently with dibenzo-24-crown-8 (1a).

Cooperative self-assembly of dendrimers via pseudorotaxane formation from a homotritopic guest molecule and complementary monotopic host dendrons.

Interaction of the homotritopic guest 1,3,5-tris[p-(benzylammoniomethyl)phenyl]benzene tris(hexafluorophosphate) (1a) with dibenzo-24-crown-8 (DB24C8) leads to the sequential self-assembly of [2]-, [3]-, and [4]-pseudorotaxanes 7a, 8a, and 9a, respectively. The self-assembly processes were studied using NMR spectroscopy. In CD(3)CN and CD(3)COCD(3) the individual association constants K(1), K(2), and K(3) for 1:1, 1:2, and 1:3 complexes were determined by several methods.

Dendritic Pseudorotaxanes.

Self-organization is the key. A series of dendritic pseudorotaxanes were efficiently constructed from complementary building blocks-namely, a three-armed, triply charged ammonium salt and the first, second, and third generations of benzyl ether dendrons bearing the dibenzo[24]crown-8 moiety. The pseudorotaxane arising from the third-generation dendron is shown in the picture.

Self-Organization of a Heteroditopic Molecule to Linear Polymolecular Arrays in Solution.

Like the proverbial monkey chain one heteroditopic self-complementary molecule, comprising a crown ether unit and a paraquat unit, catches a second such molecule in solution and thus by self-organization forms novel linear oligo- and polymolecular arrays (shown schematically; the crown ether unit is denoted by the ellipse, and the paraquat unit by the rectangle).