Introduction: Poly(glycerol sebacate) (PGS) has gained much attention in the area of regenerative medicine and the majority of studies have focused on the polymer synthesized from an equimolar ratio of sebacic acid to glycerol. However, unequal stoichiometric ratios could produce polymers that have advantageous chemical and physical properties. Based on our analysis of PGS synthesized from varying monomer stoichiometries, we hypothesize that the physical properties of the resultant PGS will be tunable to allow for applications to a wider range of tissue engineering applications.
Materials and Methods: All PGS was synthesized via a polycondensation reaction between glycerol and sebacic acid. Reactors were charged with variable molar ratios of glycerol to one molar equivalent of sebacic acid and 3 molar equivalents of water. The ratios of glycerol to sebacic acid were 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, and 1.3. The reactors were heated to 140°C under flow of N2 and stirred until the sebacic acid was melted. The temperature was then set to 120°C and held under N2 flow for 24 hours, then 130°C and under vacuum (~10 Torr) for 26 hours.
The resultant resins were characterized by gel permeation chromatography (GPC), residual acid value titration, and oscillatory rheometry.
Results and Discussion: GPC chromatograms (Fig. 1) of the PGS resins show a trend of decreasing Mw and Mw/Mn values with increasing glycerol:sebacic acid ratio. This indicates that the polymer chains self-terminate in excess glycerol, leading to a higher concentration of low Mw polymers.
This is confirmed by the residual acid value titration showing a trend of decreasing residual acid with increasing glycerol content. Oscillatory rheometry amplitude sweeps (Fig. 2) performed at 25°C show increasing storage (G') and loss (G") moduli with increasing glycerol ratio. At ratios above 0.8, G' dominates G" resulting in an elastic solid. The yield strain of the polymer also increases with increasing glycerol, indicating that the elasticity of the polymer is increasing.
Conclusions: Polymerization of PGS with varied monomer stoichiometric ratios results in a change of the physical characteristics of the resulting polymer. Acid values, Mw, and elasticity decreased and stiffness increased with increasing glycerol:sebacic acid ratios. PGS synthesized with equimolar glycerol:sebacic acid ratio exhibits a fixed relationship between Mw, acid value, and mechanical properties. Adjusting the glycerol:sebacic acid ratio shows the possibility to tune the molecular weight and mechanical properties of the polymer independently of the acid functionality. In addition to controlling the Mw of PGS, the functional group concentration (acid number) can also be tuned to allow for varying concentrations of additives to be covalently bound to the polymer matrix. This can have a broad impact on the tunability of PGS through changes in Mw, elasticity, degradation, and release kinetics of loaded drugs for various tissue engineering applications.