Different methods of synthesizing poly(glycerol sebacate) (PGS): A review

Abstract

Poly(glycerol sebacate) (PGS) is a biodegradable elastomer that has attracted increasing attention as a potential material for applications in biological tissue engineering. The conventional method of synthesis, first described in 2002, is based on the polycondensation of glycerol and sebacic acid, but it is a time-consuming and energy-intensive process. In recent years, new approaches for producing PGS, PGS blends, and PGS copolymers have been reported to not only reduce the time and energy required to obtain the final material but also to adjust the properties and processability of the PGS-based materials based on the desired applications. This review compiles more than 20 years of PGS synthesis reports, reported inconsistencies, and proposed alternatives to more rapidly produce PGS polymer structures or PGS derivatives with tailor-made properties. Synthesis conditions such as temperature, reaction time, reagent ratio, atmosphere, catalysts, microwave-assisted synthesis, and PGS modifications (urethane and acrylate groups, blends, and copolymers) were revisited to present and discuss the diverse alternatives to produce and adapt PGS.

Keywords: PGS-based materials; enzymatic synthesis; microwave-assisted synthesis; poly(glycerol sebacate) (PGS); polycondensation synthesis.

FIGURE 1

Schematic of the polycondensation of glycerol and sebacic acid to produce poly(glycerol sebacate) (PGS) and possible structures in the polymer chains. “R” = undefined polymer chain.

FIGURE 2

(A) Map showing the relationship between the degree of esterification and the state of the sample. The filled squares represent the time and temperature values for thermal treatment where the measurement of the degree of esterification and the physical state of each sample was examined. (B) Pictures of five samples at ambient temperature: A, brittle opaque wax; B, soft translucent wax; C, viscous translucent liquid; D, soft sticky elastomers; E, non-sticky elastomers. The five large squares with letters on top in (A) represent the thermal treatment conditions for the samples shown in (B). Reproduced from Li et al. (2015).

FIGURE 3

Evolution of the degree of esterification (DE), mass loss (Δm), and glycerol loss values with increasing prepolymerization time during microwave heating (Li et al., 2015).

FIGURE 4

Proposed images of the possible structures of PGS prepolymerized via microwave and conventional methods. Dashed line: cross-linking. Images inspired by Lau et al. (2017).

FIGURE 5

Thermogravimetric analysis: variation in reagent weight and biopolyesters under nitrogen flow with a heating ramp of 10°C/min (Coativy et al., 2016)

FIGURE 6

Synthesis schemes for PGS prepolymer and PGS-Methacrylate (PGS-M). Scheme from Pashneh-Tala et al. (2018).

FIGURE 7

Methacrylated PGS nerve guidance conduits: the left is compressed to highlight the elastic properties, while the right shows the final 3D-printed product ready for implantation (Singh et al., 2018).

FIGURE 8

PGS-M 3D structures produced by DLW-2PP. Images collected and adapted from Pashneh-Tala et al. (2018).

FIGURE 9

Reaction scheme for PGSU synthesis using HDI as a pre-PGS cross-linker. Scheme inspired by Pereira et al. (2013).