Biodegradable comb-dendritic tri-block copolymers consisting of poly(ethylene glycol) and poly( l-lactide): Synthesis, characterizations, and regulation of surface morphology and cell responses

Abstract

A series of well-defined dumbbell-shaped tri-block copolymers consisting of comb-like poly( l-lactide) (PLLA) and linear poly(ethylene glycol) (PEG) with narrow molecular weight distributions and varied PLLA arm lengths have been synthesized via the sequential preparation of terminal dendronized polyhydric PEG and ring-opening polymerization (ROP) of l-lactide (LA). The terminal dendronized polyhydric PEG was prepared by the conjugation of amine-terminated fourth-generation polyester dendrons with NHS-activated PEG followed by the deprotection of acetonide groups. The length of PLLA arms can be readily controlled by the feed molar ratio of LA monomer to the hydroxyl groups in PEG macro-initiator. Differential scanning calorimetric (DSC) measurements and thermal gravimetric analysis (TGA) have been performed to indicate that the glass transition temperature ( T g), melting point ( T m), degree of crystallinity ( χ c), and onset decomposition temperature ( T d) of the copolymers are lower than those of the linear polylactide (LPLLA). Self-organized porous structures have been found in the copolymer films after solution casting and solvent evaporation. Honeycomb-like surface morphology could be achieved by adjusting the length of PLLA arms. Meanwhile, surface chemistry of the copolymer films such as surface hydrophobicity and the capability of adsorbing protein increase with the length of PLLA arms. Controllable material properties have been correlated with the in vitro cell responses. No cytotoxicity of the dumbbell-shaped copolymers has been found using rabbit bone marrow stromal cells (BMSCs). Human embryonic kidney (HEK) 293T cells have been used to reveal the effect of surface characteristics on cell attachment and proliferation. It has been found that cell proliferation has been enhanced significantly on the surfaces of the copolymers with longer PLLA arm lengths because of more favorable surface physicochemical properties.