Binary system thermodynamics to control pore architecture of PCL scaffold via temperature-driven phase separation process

Abstract

The use of scaffold-aided strategies for the regeneration of biological tissues requires the fulfilment of an accurate architectural design, that is, micro and macrostructure, with the final goal of realizing architectures to adopt as guidance for those cell activities specific to the formation of novel tissues. Here, highly porous scaffolds made up of biodegradable poly(ε-caprolactone) (PCL) have been realized by thermally induced phase separation (TIPS). Two different polymer/solvent systems, derived by the dissolution of PCL in dioxane and DMSO respectively, were investigated. The aim was to demonstrate the high potential of TIPS technique, in imprinting specific pore features to the polymer matrices, by a conscious selection of polymer/solvent systems. The investigation of pore architecture by SEM/mercury intrusion porosimetry/image analyses, firstly allow to detect remarkable variations in porosity (from 92% to 78%,) and pore sizes, ranging from micro-scale (ca 10 µm) to macro-scale (greater than 100 µm) as a function of the used polymer/solvent systems. Moreover, experimental and theoretical evidences referred to scaffold shaped in custom-made molds--a thin Teflon ring between two copper plates--allow exploring how the sensitivity of polymer solution features (i.e., crystallinity, thermal inertia) to the cooling temperature can affect the alignment of polymer phases and, ultimately, scaffold pore anisotropy. Analytical results supported by preliminary biological studies demonstrate the higher ability of PCL/dioxane solution to promote the formation of aligned pores which provide a morphological guidance to cell advance during the preliminary stage of culture. These findings, taken as a whole, put the basis for a better informed regeneration of structurally complex tissues based on the modeling of scaffold micro and macro-architecture by thermodynamic forces.