A route to aliphatic poly(ester)s with thiol pendant groups: from monomer design to editable porous scaffolds

Biodegradable aliphatic polyesters such aspoly(lactide) and poly(ε-caprolactone), largely used in tissueengineering applications, lack suitable functional groups andbiological cues to enable interactions with cells. Because of theubiquity of thiol groups in the biological environment and thepliability of thiol chemistry, we aimed to design and synthesizepoly(ester) chains bearing pendant thiol-protected groups. Toachieve this, 3-methyl-6-(tritylthiomethyl)-1,4-dioxane-2,5-dione, a lactide-type monomer possessing a pendant thiolprotectedgroup, was synthesized. This molecule, when used asa monomer in controlled ring-opening polymerization incombination with lactide and ε-caprolactone, appeared to be a convenient “building block” for the preparation of functionalizedaliphatic copolyesters, which were easily modified further. A polymeric sample bearing pyridyl disulfide groups, able to bind acysteine-containing peptide, was efficiently obtained from a two-step modification reaction. Porous scaffolds were then preparedby blending this latter copolymer sample with poly(L-lactide-co-ε-caprolactone) followed by salt leaching. A further disulfideexchange reaction performed in aqueous medium formed porous scaffolds with covalently linked arginine-glycine-aspartic acidsequences. The scaffolds were characterized by thermal and mechanical tests, and scanning electron microscopy surface imagesrevealed a highly porous morphology. Moreover, a cytotoxicity test indicated good cell viability.