An Innovative One-Step Method to Produce Membranes with a Pore Size Gradient

The fabrication of porous scaffolds with continuous pore size gradients is growing in interest in tissue engineering, as graded architectures better mimic the structural heterogeneity of native interfacial tissues. Conventional strategies based on monolayer scaffolds fail to reproduce this heterogeneity, while multilayer constructs introduce interfaces that do not ensure continuous transitions in structural and mechanical properties. Although most gradient fabrication approaches rely on multistep or post-processing techniques, limited attention has been focused to procedures allowing to obtain directly the final scaffold. Thermally induced phase separation is a versatile method for regulating pore morphology in scaffold by controlling the thermal history. This work investigates a TIPS-based strategy to generate continuous pore size gradients by tailoring heat transfer directionality. Poly-L-lactic acid scaffolds were produced using two process configurations differing in the presence or absence of thermal insulation and analysed using a combined experimental and numerical approach. Scaffold morphology was characterised by scanning electron microscopy, while thermal transient simulations were performed to investigate temperature evolution during phase separation and freezing. The analysis highlights differences in cooling behaviour between the two configurations, correlating these with variations in pore size distribution across the scaffold thickness. The results demonstrated that it is possible to obtain scaffold with a pore size gradient through a one-step TIPS procedure.