RESOURCES

Abstract
The fabrication of three-dimensional (3D) scaffolds with imprinted physical{,} chemical and topographical cues is instrumental in tissue engineering strategies to instruct cell function and guide the regeneration of tissues. α-Amino acids based poly(ester amide)s (AAA-PEAs){,} combining the biocompatibility and biodegradability of polyesters with the superior mechanical properties of polyamides{,} have emerged as promising scaffolding materials. However{,} their processing via extrusion-based 3D printing remains challenging due to the lack of polymeric structures with suitable molecular weight and thermal stability. Here{,} we develop a new library of high molecular weight AAA-PEAs based on l-alanine (PEA-ala){,} l-alanine/glycine (PEA-ala–gly (75 : 25)) and l-alanine/glycine/jeffamine (PEA-ala–gly–jeff (50 : 25 : 25)) and investigate their performance as polymeric materials for 3D printing against commercially available poly(ε-caprolactone) (PCL). Thermogravimetric analysis reveals the stability of AAA-PEAs at high temperatures{,} enabling their processing via melt-extrusion printing. Despite differences in complex viscosity between PCL and AAA-PEAs{,} highlighted by oscillatory rheology measurements{,} the printability of AAA-PEAs does not seem to be compromised{,} resulting in 3D scaffolds with good shape-fidelity. Additional physicochemical characterisation of synthesised materials also confirm the possibility of fabricating two-dimensional (2D) films and 3D scaffolds with different mechanical properties{,} wettability and degradation profiles{,} depending on the AAA-PEA used. Biological tests carried out in vitro confirm the ability of synthesised materials to support the adhesion and function of metabolically active human bone marrow derived mesenchymal stem cells (hBM-MSCs). The newly synthesised AAA-PEAs expand the range of processable materials via melt-extrusion and contribute to the fabrication of scaffolds with tuneable physicochemical properties for improved tissue regeneration.

Abstract
The current research reports for the first time the use of blends of poly(ε-caprolactone) (PCL) and poly(ester amide) (PEA) for the fabrication of 3D additive manufactured scaffolds. Tailor made PEA was synthesized to afford fully miscible blends of PCL and PEA using different percentages (5, 10, 15 and 20% w/w). Stability, characteristic temperatures and material's compatibility were studied through thermal analyses (i.e., TGA, DSC). Even though DMTA and static compression tests demonstrated the possibility to improve the storage modulus, Young's modulus and maximum stress by increasing the amount of PEA, a decrease of hardness was found beyond a threshold concentration of PEA as the lowest values were achieved for PCL/PEA (20% w/w) scaffolds (from 0.39 ± 0.03 GPa to 0.21 ± 0.02 GPa in the analysed load range). The scaffolds presented a controlled morphology and a fully interconnected network of internal channels. The water contact angle measurements showed a clear increase of hydrophilicity resulting from the addition of PEA. This result was further corroborated with the improved adhesion and proliferation of human mesenchymal stem cells (hMSCs). The presence of PEA also influenced the cell morphology. Better cell spreading and a much higher and homogenous number of cells were observed for PCL/PEA scaffolds when compared to PCL ones.