Unveiling the Role of Key Parameters during Molecular Growth for Optimal Poly(glycerol sebacate) Synthesis

Abstract Poly(glycerol sebacate) (PGS) belongs to the hyperbranched polyesters family (HBP), which possesses an extensive variety of applications due to its tunable chemical and mechanical properties, together with its biocompatibility and biodegradability. However, the understanding of PGS synthesis becomes a challenge due to the lack of consistency when determining its synthesis parameters. Understanding these parameters is fundamental to control PGS synthesis and obtain a scalable and reproducible final product for biomedical applications. To unveil their effect on diverging PGS properties, diols are used as glycerol analogs and the reaction is chemically and thermally monitored, suggesting a heterogeneous reactivity of the exposed hydroxyl groups. Also, confinement of the prepolymerization is proven to be fundamental In order to maintain the equimolar ratio of initial monomers during synthesis. Early stages of the polycondensation (first 4 h) tend to linear and less branched oligomers by consuming primary hydroxyls rather than secondary hydroxyls. However, physicochemical characterization determines that a high degree of conversion (40%) is reached during these early stages. Afterward, the oligomers tend to condense through the secondary hydroxyls into a more crosslinked elastomer. This study demonstrates how hydroxyl affinity, water presence, and glycerol loss are crucial for the scalability and reproducibility of its final product.