Vinyl sulfonate terminated star-shaped polyglycidols for biomedical applications

This thesis introduces vinyl sulfonate terminated, star-shaped polyglycidols as a novel biomaterial for various kinds of applications. Polyglycidols, highly functional polymers with hydroxymethyl side groups, fulfill all structural prerequisites to replace poly(ethylene glycol)s in medical applications. Architecturally well defined polyglycidols with both linear and star-shaped structure and molecular weights up to 20 000 g mol-1 are prepared in an anionic polymerization procedure using ethoxyethyl glycidyl ether as monomer. Subsequently, these polymers are end-group functionalized by treatment with 2-chloroethylsulfonyl chloride leading to the formation of vinyl sulfonate terminated poly¬(ethoxy¬ethyl glycidyl ether)s (VS-sPEEGEs). The acetal protecting group can be easily removed by treatment with hydrochloric acid to form vinyl sulfonate terminated polyglycidols (VS-sPGs) without affection of the functionality. Both vinyl sulfonate terminated polymers show high reactivity towards the formation of conjugates with amines. The successful addition of amines to the polymers can be easily monitored by NMR spectroscopy. Due to the mild reaction conditions, the use of vinyl sulfonate terminated polymers for biomedical applications is promising and there usage in three different biomedical applications was investigated. Bulk hydrogels based on VS-sPG are prepared using poly(ethylene imine) (PEI), poly(allyl amine) (PAAm) or poly(L-lysine) (PLL) as polyamine. For all three polymers, stable hydrogels are achieved by addition reaction of VS-sPG with the corresponding polyamines leading to a crosslinked network. Nanofibers based on sPEEGE are obtained by usage of the electrospinning process. As sPEEGE is a highly viscous but still liquid polymer, stable fibers can only be obtained by using a polymer blend containing up to 35 wt.% sPEEGE and poly(epsilon-caprolactone) as copolymer. By variation of the amount of sPEEGE within the polymer blend as well as by adaption of the process parameters, highly hydrophilic and biocompatible polymer fibers with tremendously decreased protein adsorption are prepared. Surface reactive nanofibers are formed using polymer blends containing functionalized sPEEGE, e.g. vinyl sulfonate or alkyne terminated sPEEGE. Fibers formed from polymer blends containing VS-sPEEGE show high surface reactivity towards amines and can be biofunctionalized by simple immersion of the fiber mesh in an aqueous solution of the bioactive compound. By attachment of short peptide sequences, e.g. GRGDS, to the surface of the nanofiber meshes the interaction between cells and the nonwoven can be tailored towards their use in tissue engineering applications. Vinyl sulfonate terminated polymers can further be applied as surface coating. Both VS-sPEEGE and VS-sPG form stable polymer layers either by dip- or spin-coating from organic or aqueous solutions depending on the solubility of the polymers. Interestingly, high protein repelling properties are achieved using VS-sPEEGE, while coatings derived from VS-sPG still exhibit unspecific protein adsorption on their surface. This is astonishing as VS-sPG is more hydrophilic compared to VS-sPEEGE. One potential explanation might be an incomplete coating, another one the possibility of hydrogen bonding between the polymer layers and the applied proteins. None the less, both types of polymers show high biocompatibility and no negative effects on the growth of cells are observed. Nonadhesive, antibacterial wound dressings are prepared by using the established hydrogel system based on isocyanate terminated star-shaped poly(ethylene oxide-stat-propylene oxide) (NCO-sP(EO-stat-PO)). By application of nanoscopic layers of NCO-sP(EO-stat-PO) on the surface of commercial, cellulose based wound dressings, the adhesion force is reduced to 2 to 5 % compared to non-treated nonwovens. To support the wound healing process, the hydrogel layer can be further loaded with arginine. The growth of different cells, e.g. fibroblast, is up to three times faster upon contact with arginine loaded nonwovens compared to arginine-free samples. Additionally, nano-silver particles are embedded within the hydrogel layer reducing significantly the growth of E.coli. All modifications of the nonwovens are highly biocompatible and no toxic effects of the wound dressings are observed by in-vitro investigations