Design and optimization of hybrid formulations based on PLLA and inorganic phases for 3D printing of bone scaffolds

The present work is framed within the H2020 GIOTTO project whose general aim is to develop medical devices able to stimulate bone regeneration in compromised clinical situations as osteoporotic fractures. To this aim, substituted nano-hydroxyapatites (nano-HAs) and mesoporous bioactive glasses (MBGs) are excellent candidates to promote bone healing due to their inherent bioactivity and ability to release selected ions able to stimulate bone production (e.g. strontium ions). These bioactive materials can be combined with bioresorbable matrices to design 3D scaffolds able to stimulate physiological bone remodelling while ensuring the structural support needed to assist and guide fracture healing. In particular, the thesis focussed on the production and fully characterization of bioactive inorganic phases, followed by their dispersion into a resorbable polymer matrix to produce hybrid formulations with the desired resorption kinetics and the ability to be processed by 3D printing technologies. The research work related to the combination of the selected polymer and inorganic phases, the filament extrusion and the mechanical properties assessment, was conducted at Newcastle University, Newcastle Upon Tyne, UK, under the supervision of Prof. Kenny Dalgarno, one of the partners of GIOTTO consortium. In this work, MBG containing strontium ions (10%molar) were produced through two different synthesis routes, a batch sol-gel in basic medium (SG) and a spray-drying aerosol-assisted sol-gel procedure (SD). The characterization revealed that both MBGs displayed a spherical morphology, pore sizes (2-10 nm) in the range of mesoporous materials (2-50nm) and specific surface area (190-220m2/g) greatly higher than non-mesoporous materials. Strontium substitution was successful as evidenced by Energy dispersive X-ray Spectroscopy (EDS) which revealed a Sr content close to the theoretical values and the ion release test confirmed the MBGs ability to fully release incorporated Sr ions. Nano-HA phases were provided from a project partner with different degrees of strontium ion substitution (0–50–100%). EDS characterization confirmed a successful strontium ion substitution. Morphological analysis revealed that nano-HA particle size increased while increasing strontium content, most likely due to the greater Sr ion dimension. The (Ca+Sr)/P ratio in all samples was similar to the stoichiometric ratio of typical HA. Poly L-lactic acid (PLLA) was selected as the polymeric phase, due to its good mechanical properties and well-known biocompatibility. The polymer pellets were combined with a water suspension of the developed inorganic phases and extruded into a consistent filament. EDS analysis showed that the included phases and ions were regularly dispersed across the polymer section. The composite polymers show ed a more brittle behaviour compared to PLLA matrix, but the overall mechanical properties were not negatively affected by the incorporated inorganic phases. The rheological assessment, performed at 220°C to explore the material properties at the extrusion temperature, revealed a similar viscoelastic behaviour for all the tested composites and PLLA alone. The samples exhibited a liquid-like state indicated by higher values of loss modulus (G’’) compared to storage modulus (G’) at low frequencies. Also, flow ramps displayed high viscosities for all the processed materials at low shear rates, where lower values were reported in case of PLLA-MBG combination.