Synthesis of photopolymerizable macromers giving novel poly(β-amino ester)s for biomedical applications

Biodegradability, hemocompatibility, protein adsorption resistance, and strong interactions with hydroxyapatite (HAP)-based tissues such as dentin, enamel, and bone are properties that make phosphorus-containing biomaterials relevant and important. Here, novel phosphonate-functionalized poly(-amino ester) (PBAE) macromers are synthesized through aza-Michael addition of various diacrylates [1,6-hexane diol diacrylate (HDDA), poly(ethylene glycol) diacrylate (PEGDA, Mn=575), 1,4-butane diol diacrylate (BDDA), 1,6-hexanediol ethoxylatediacrylate (HDEDA), triethyleneglycoldiacrylate (TEGDA)] and two phosphonate-containing primary amines [diethyl 2-aminoethylphosphonate (A1) and diethyl (6-amino hexyl) phosphonate (A2)] efficiently without any catalyst. Macromers prepared from Michael addition of the same acrylates with propyl amine (PA) were used as references. The molecular weights of the macromers were ca. 2000-3000, confirmed by both gel permeation chromatography and 1H-NMR spectroscopy. The macromers were used for free radical photopolymerization in the presence of 2,2-dimethoxy-2-phenylacetophenone as photoinitiator and under UV light to give biodegradable gels and the gels' properties (degradation and cell interactions) were studied. The mass loss and cell interactions of the polymers were found to be affected by the chemical structure of the polymers. Polymers based on HDDA, BDDA and HDEDA showed similar and very low mass losses (3-15 % after two weeks) due to their hydrophobic backbone structures. The highest mass losses were observed for PEGDA-based macromers (40-50 % after two weeks). Some of the phosphonate-functionalized PBAE polymers were found to support attachment of SaOS-2 cells better than nonphosphonated ones.