Synthesis, characterization and surface modification of low moduli poly(ether carbonate urethane)ureas for soft tissue engineering.

Abstract

Flexible scaffolds are of great interest in engineering functional and mechano-active soft tissues as such scaffolds might allow mechanical stimuli to transfer effectively from the scaffolds to cells during tissue development. Towards this end, we have developed a family of flexible poly(ether carbonate urethane)ureas (PECUUs) with a triblock copolymer poly(trimethylene carbonate)-poly(ethylene oxide)-poly(trimethylene carbonate) (PTMC-PEO-PTMC) or pentablock copolymers PTMC-PEO-PPO-PEO-PTMC (PPO, polypropylene oxide) as soft segments, linked by 1,4-diisocyanatobutane and putrescine. All of the PECUUs had low glass transition temperatures (<-46 degrees C). The PTMC-PEO-PTMC-containing PECUUs had low tensile strength and breaking strain. Replacing PEO with the similar length PEO-PPO-PEO resulted in highly flexible and soft PECUUs possessing breaking strains of 362-711%, tensile strengths of 8-18MPa and moduli of 5.5-7.4MPa at room temperature in air. Under aqueous conditions at 37 degrees C, these polymers remained flexible while their moduli were decreased to 3.4-4.0MPa. PECUUs based on PTMC-PEO-PPO-PEO-PTMC were thermosensitive as the water content at 37 degrees C was lower than that at 4 degrees C. PECUU using PTMC-PEO-PTMC as a soft segment showed 30% weight loss over 6weeks in PBS at 37 degrees C, while that using PTMC-PEO-PPO-PEO-PTMC as a soft segment had weight loss <6%. Degradation products were found to lack cytotoxicity. The mechanical stresses and moduli of PECUUs based on PTMC-PEO-PPO-PEO-PTMC were unchanged during the degradation. To enhance cell adhesion, PECUUs were surface modified with Arg-Gly-Asp-Ser (RGDS). Smooth muscle cell adhesion was 114% of tissue culture polystyrene for unmodified PECUU and >180% for RGDS-modified PECUUs, with cell viability on both surfaces increasing during culture. These low moduli polyurethanes may find applications in engineering cardiovascular or other soft tissues.