Novel dendrimer based polyurethanes for PEO incorporation

Abstract

A series of segmented polyurethanes based on methylene diisocyanate/poly (tetramethylene oxide) and chain extended with either ethylene diamine or butane diol in combination with a generation 2 polypropylenimine octaamine dendrimer were synthesized. For polymer synthesis, the dendrimers were protected with either t-boc or Fmoc groups and were incorporated into the polyurethane microstructure to permit further functionalization with biologically active groups. Following deprotection, the dendrimers were reacted with succinimidyl propionate polyethylene oxide (SPA-PEO) to improve the protein resistance of the polymers and to examine the potential of this technique for polymer functionalization. Different synthesis techniques were examined to optimize the incorporation of the PEO into the polymer microstructure. Incorporation of the dendrimers and the PEO were confirmed by NMR and FTIR. Gel permeation chromatography was used to examine the molecular weights of the various polyurethanes. The dendrimer incorporated polymers had significantly lower molecular weights than the ED or BDO chain extended controls, likely due to lower reactivity of the dendrimers as a result of steric factors. Following PEO reaction, the molecular weights of the resultant polymers were consistent with the levels of PEO incorporation noted by comparison of peak intensities in the NMR spectra. Due to the highly hydrophilic nature of the PEO, some migration to the polymer surface was expected. Water contact angles and XPS, used to characterize the surfaces, suggest that there was some PEO enrichment at the surface of the polymers. Adsorption of radiolabeled fibrinogen to the polymer surfaces was decreased by a factor of approximately 40% in some of the PEO incorporated polymers. There were also differences in the patterns of plasma protein adsorption on the various surfaces as evaluated by SDS PAGE and immunoblotting. Therefore, the use of dendrimers in biomaterials for incorporation of a large number of functional groups seems to be promising.

Regulation of polyurethane hemocompatibility and endothelialization by tethered hyaluronic acid oligosaccharides

“…While further testing of these HA-modified materials will be needed in order to verify their potential for use in vascular applications, the in vitro tests reported herein have been promising, demonstrating the ability of PU grafted with low molecular weight HA to reduce protein adsorption and platelet adhesion while promoting endothelialization and retaining vascular-appropriate mechanics. A number of different methods can be used to introduce functional groups to PU, such as functionalization of the bulk material or surface activation with various reactive monomers [32]. Surface modification methods are usually based on radiofrequency-generated gas plasmas [29], but the plasma-treated surfaces become unstable upon exposure to air and experience rapid changes in their surface characteristics.…”

Partitioning of model toxins to hydrophobically terminated DAB dendrimers

“…Dendrimers have been studied as gene (Haenseler and Szoka (1993); Kukowska-Latallo et al, (1996); Bielinska et al, (1997); Bielinska et al, (1999); Bielinska et al, (2000)) and drug delivery (Barth et al, (1994); Kono et al, (1999); Liu et al, (2000); ; ) vehicles, as well as for cellular recognition, cell adhesion and cell growth regulation (Zanini et al (1995); Zanini and Roy (1997); Kawase et al (2001)). They have also been used for the modification of biologically relevant polymeric materials to increase the density of relevant functional groups (Duan et al (2002)). These studies suggest that dendrimers are generally biologically acceptable, which is thought to be due in part to the similarity of their size and shape to many biological components.…”

“…Dendrimers have been shown to modify gold surfaces and these surfaces have been suggested to have various applications (Rahman et al (2000); Zhao et al (1999); Tokuhisa et al, (1998);Liu et al (1997)). We have previously demonstrated that dendrimers can be incorporated into the structure of polyurethanes and polyurethane ureas and can be subsequently functionalized with polyethylene oxide (PEO) chains (Duan et al (2002)). The incorporation of a relatively small amount of dendrimer into the polyurethane structure during the chain extension step and its subsequent functionalization with PEO resulted in a significant (40%) decrease in the adsorption of fibrinogen and decreases in the adsorption of other plasma proteins.…”

Thiol-Ene Click-Inspired Late-Stage Modification of Long-Chain Polyurethane Dendrimers

“…In contrast, the second route described by Kumar and Ramakrishnan [38] employed an isocyanate-free approach to synthesize polyurethane dendrimers. Following these pioneering works, a few more dendritic polyurethanes have been reported [39][40][41][42][43][44][45][46]. More recently, Nasar and coworkers have reported the synthesis of hyperbranched polyurethanes and polyurethane dendrimers based on blocked isocyanate chemistry [47][48][49][50][51][52].…”

“…First reported by Hawker and Fréchet for the synthesis of poly(phenyl benzyl ether) dendrimers, ref [54] the convergent method ensures the precise placement of functional groups throughout the dendritic structure that enables the synthesis of functional macromolecules. Though several dendrimers are reported recently employing the convergent method of synthesis, refs [21,24,[54][55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70][71][72] there are very few reports on polyurethane dendrimers using this method [40,[73][74][75].…”