Poly(3-hydroxybutyrate-co-3-hydroxyexanoate) scaffolds with tunable macro- and microstructural features by additive manufacturing.

Polymer microstructural engineering by additive manufacturing (AM) represents a powerful tool to functionalize tissue engineering scaffolds. This article reports on the processing of polymer/solvent/non-solvent ternary mixtures through their extrusion in a non-solvent bath as an innovative phase inversion-based AM approach to engineer poly(3-hydroxybutyrate-co-3-hydroxyexanoate) (PHBHHx) scaffolds porosity. The processing of PHBHHx mixtures with different chloroform/ethanol ratio into scaffolds characterized by a dual-scale porosity is described by highlighting how an interconnected network of macropores can be endowed with a tunable microporosity, formed a result of the phase inversion process governing polymer solidification. In particular, the study demonstrates that varying the non-solvent percentage in the ternary mixture represents an effective means to tailor the macropores size along scaffold vertical cross-section and the local micropores concentration in the polymer matrix. These structural changes are demonstrated to significantly affect scaffold overall porosity and tensile modulus, as well as its ability to support in vitro the proliferation of preosteoblast cells. The developed manufacturing strategy combines an advanced material engineering method effective on dual-scale size levels, with a modern approach to the sustainable processing of naturally-derived polyesters that minimizes the employment of halogenated solvents.