Rapid and Efficient Optimization of Poly(1,2-Ethanediol Citrate) Synthesis Based on Magic Squares’ Various Methods

New biomaterials among aliphatic polyesters are in demand due to their potential applications in tissue engineering. There is a challenge not only to design scaffolds to regenerate defects in load-bearing tissues but also to ensure a proper blood supply to the reconstructed tissues. Poly-(1,2-ethanediol citrate) is one of the novel citrate-based polymers that could have the desired properties for cell scaffold fabrication and for enhancing cell adhesion. Both citric acid and 1,2-ethanediol are used in medicine and are fully resorbable by cells. This work aimed to synthesize poly(1,2-ethanediol citrate) in a catalyzed reaction with water removed by the Dean–Stark apparatus. The polyester structure was characterized by FTIR and NMR spectroscopy, and the HMBC experiment was performed to support the theory of successful polymer synthesis. The molecular weight was determined for the products obtained at 140 °C. The process was described via non-linear mathematical models. The influence of temperature and catalyst content on the degree of esterification and the conversion of acid groups in citric acid is described. The optimal process parameters are determined at 140 °C and 3.6% of p-toluenesulfonic acid content. The presented results are the starting point for scaffold design and scaling-up the process.