Post-manufacture loading of filaments and 3D printed PLA scaffolds with prednisolone and dexamethasone for tissue regeneration applications

Abstract

Strategies to load prednisolone or dexamethasone in preformed poly(L-lactic acid) (PLA) filaments and 3D printed scaffolds were explored as a way of personalizing the drug, the dose and the release profile for regenerative medicine purposes. Instead of starting from a PLA filament preloaded with a given content of drug, we explored two more versatile strategies. The first one involved the soaking of PLA filaments into a drug solution prepared in a solvent that reversibly swelled PLA; during 3D printing the melting of PLA contributed to the efficient integration (encapsulation) of the drug inside the printed strand. The second strategy consisted in first printing the 3D PLA scaffolds followed by soaking in a suitable drug solution in order to exploit the higher specific surface of the printed strands compared to the filament. Sustained release profiles were recorded when either prednisolone or dexamethasone were loaded in preformed PLA filaments, while rapid release was recorded for 3D PLA scaffolds loaded after printing. The combination of the two proposed methods reported here opened the possibility of creating concentration gradients of different drugs in the same scaffold exhibiting distinct release patterns. Namely, the strand core contained an active ingredient to be slowly released, while the surface was covered with other active ingredient that could be rapidly delivered. The feasibility of this approach was confirmed through dual loading of dexamethasone in the filament and of prednisolone on the preformed scaffold. Drug-loaded scaffolds were characterized in terms of printability, structural characteristics (DSC, XRD), mechanical properties, biodegradation, and ability to promote cell attachment and proliferation. Finally, anti-inflammatory response and osteoinductive properties were verified in cell cultures.