Synthesis, swelling, degradation and cytocompatibility of crosslinked PLLA-PEG-PLLA networks with short PLLA blocks

Abstract

A series of triblock macromonomers with the general structure PLAa-PEGb-PLAa with acrylate end-groups and very short segments of PLA have been synthesized and characterized for potential use in the treatment of periodontitis. In the proposed application aqueous solutions of the triblock macromonomers would be injected into the pockets formed around the teeth and then crosslinked via photo-induced free radical polymerization to form drug-laden hydrogels. One of the macromonomers with the structure PLA4-PEG45-PLA4 showed optimum properties for the proposed application and was chosen for a more detailed study. In the study, the nature of the hydrogels formed by the macromonomer and by its copolymerization with PEG16 diacrylate has been investigated, along with its swelling and degradation in PBS at 37°C and pH 7.4. The hydrogels swell to equilibrium in water or PBS within approximately 5h, with swelling ratios in the range 4.5–3.5 and penetrant diffusion coefficients 1.5–2.4×106cm2s−1in PBS, depending on the PLA4-PEG45-PLA4 macromonomer content over the range 1.00–0.80wt fraction. The swollen hydrogels have an open pore structure, with the diameter of the largest pores in excess of 25μm. A detailed spectroscopic study confirmed that degradation in PBS proceeds as expected via hydrolysis of the lactide segments, and the polymer matrix completely dissolves after ≈22 days. The potential for control of degradation kinetics using the comacromonomer composition was also demonstrated. The cytotoxicity towards fibroblasts and osteoblasts, two important cell types involved in tissue repair and bone regeneration, has also been thoroughly evaluated. The hydrogels, and the products of hydrolytic degradation, were found to be non-cytotoxic towards these particular cells.