Design and synthesis of maleimide-containing biofunctionalizable nanofibers

Abstract

Polymeric nanofibers have gained great attention lately due to their unique properties, which makes them attractive candidates for usage in many applications. These properties include high surface area, porosity, encapsulation efficiency and loading capacity, controllable scaffold composition and physical resemblance to the extracellular matrix. Polymeric nanofibers are commonly obtained using electrospinning, an easy and low-cost method. The nanofibers used in biological applications usually need modifications with various (bio)molecules in order to increase biocompatibility. Most nanofibers lack specific functional groups that are needed for conjugating ligands and biomolecules. Recent approaches involve incorporation of clickable units on nanofibers to allow their functionalization in an efficient manner. In the present study, we explored the formation of maleimide-containing nanofibers, which can be functionalized with thiol-containing ligands under reagent-free conditions at room temperature using the Michael reaction. Copolymers containing poly(ethylene glycol) and furan-protected maleimide-containing polylactide based copolymers were synthesized via organobase-catalyzed ring-opening polymerization. The furan protection was removed after polymerization using retro Diels-Alder reaction, to obtain the reactive maleimide functionality. PEG side chains were incorporated to provide anti-biofouling characteristics to these copolymers. Maleimide-bearing nanofibers were produced using the solutions electrospinning. Efficient functionalization was demonstrated by modification of these nanofibers with a thiol-containing fluorescent dye and a thiol-containing biotin ligand. The biotinylated nanofibers were used for the immobilization of TRITC-extravidin using the biological interaction between biotin-avidin. Importantly, it was demonstrated that the extent of immobilization of protein on these nanofibers can be tuned by varying the amount of „clickable‟ reactive groups on the nanofibers, which can be tailored through the composition of the parent copolymer.