Mapping the synthesis and the impact of low molecular weight PLGA-g-PEG on sol–gel properties to design hierarchical porous scaffolds

Bone morphogenetic protein 2 (BMP-2)-functionalized poly(l-lactide-co-ε-caprolactone) (PLCL) porous scaffolds have shown promising results in bone tissue regeneration studies. It is believed that even better results are achieved by hierarchical porous scaffolds and a designed sequential release of growth factors. We therefore synthesized (l-lactide-co-glycolide)-g-poly(ethylene glycol) (PLGA-g-PEG) oligomers which could be injected into PLCL porous scaffolds. They were synthesized by ring-opening polymerization and carefully characterized by nuclear magnetic resonance spectroscopy (NMR), matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS), and size exclusion chromatography (SEC). The sol–gel transition temperature, pH, and functional life were determined and correlated with the molecular structure of PLGA-g-PEG. We found that low molecular weight PLGA-g-PEG was obtained and poly(l-lactide-co-glycolide-co-poly(ethylene glycol) methyl ether) (PLGA-MPEG) appeared to contribute to gelation. It was possible to design a system that formed a hydrogel within 1 min at 37 °C with a pH between 6 and 7 and with a functional life of around 1 month. These low molecular weight thermosensitive PLGA-g-PEG oligomers, which can be injected into PLCL scaffolds, appear promising for bone tissue engineering applications.