Bioinspired poly(ester urethane)s as constituent materials of melt-extruded scaffolds for tissue engineering

Nowadays, tissue engineering (TE) is experiencing an increasing growth in the biomedical field. In this context, 3D printing techniques represent a powerful tool to design multi-layered structs with improved mimicry potential of the native host tissue. However, these techniques require ad-hoc engineered biomaterials to satisfy specific technological parameters in addition to biocompatibility and bioactivity. Thermoplastic poly(urethane)s (PUs) can be interesting candidates in this sense, because their building blocks can be ad-hoc selected to regulate their mechanical and thermal properties. Moreover, to improve cell adhesion and biomimicry capability, these materials can also be surface functionalized with common, eco-friendly techniques such as plasma treatment and carbodiimide chemistry. In this thesis work, PUs based on poly(ε-caprolactone), PCL, a well-known biocompatible poly(ester), and 1,6-diisocyanatohexane were produced optimizing a previously developed synthesis protocol. In addition, their composition and thus physico-chemical properties were tuned using 1,4-butanediol (BHC2000), 1,8-octanediol (OHC2000) or 1,12-dodecanediol (DHC2000) as chain extenders. Infrared (IR) spectroscopy confirmed the success of the synthesis with the appearance of the characteristic urethane bond peaks at ca.3350, 1680 and 1534 cm-1. Size Exclusion Chromatography (SEC) estimated a weight average molecular weight (Mw) in the range between 40 and 50 kDa, with BHC2000 showing the highest Mw (ca.50 kDa). The most relevant effect of the selected different chain extenders was observed through mechanical tensile tests. BHC2000 showed the highest deformability, with average values of strain at break around 680%, whereas OHC2000 was the stiffest material, with a Young’s Modulus of ca.530 MPa. These differences were explained with the different crystallization of the PCL soft phase and PUs hard segments, which was also evidenced by Atomic Force Microscopy and Differential Scanning Calorimetry (DSC). DSC also evidenced that all the PUs were molten below 150 °C, as confirmed through rheological analysis. Hence, all these materials proved suitable for melt-extrusion processing techniques. Based on these results, a proof-of-concept of the printability of simple 3D structures was also performed. Finally, to increase the hydrophilicity of the PU surface and permit biomolecule grafting to improve biocompatibility, an argon/acrylic acid plasma treatment was performed. The Toluidine Blue O colorimetric assay and wettability measurements confirmed the functionalization success, with the exposure of -COOH in the order of 1015/cm2 and a reduction of the contact angle from about 90° to 50°. In addition, a carbodiimide-guided gelatin grafting was also proved possible, as assessed by the bicinchoninic acid assay, wettability measurements and IR spectroscopy. In conclusion, the PUs developed in this work present suitable characteristics for the production of TE scaffolds using additive manufacturing techniques. Given the possibility to tune their mechanical properties by a proper selection of the building blocks during the synthesis, different tissues can be targeted, such as non-load bearing bone for stiffer materials (i.e., OHC2000) or softer tissues like cartilage for more elastic ones (i.e., BHC2000). Moreover, the possibility to improve their hydrophilicity and biomimicry through versatile surface modification methods will also permit to finely tune the functionalization depending on the final selected application.