Microarchitecture of poly(lactic acid) membranes with an interconnected network of macropores and micropores influences cell behavior

Abstract

Tissue engineering scaffolds require a three-dimensional architecture with controlled pore size and structure to host tissue formation. Here we used the non-solvent induced phase separation (NIPS) process to prepare porous asymmetric membranes made of poly(lactic acid) (PLA) using dimethylformamide (DMF) as solvent and water as non-solvent. The addition of a polymer additive to the PLA solution has made it possible to increase and control the size of open macropores at the membrane bottom surface and to generate a dual pore architecture consisting of an interconnected network of macropores and micropores. Based on the study of the compatibility of PLA with the polymer additive we propose that the dual pore architecture is generated through a two phase separations process. Membrane surface could be functionalized with hyaluronan (HA) and, whatever the cell type considered, HA-functionalization enhanced cell proliferation. Interestingly, a strong effect of macropore size and surface functionalization by HA on cell colonization and cell proliferation within membranes and membrane morphology on cell organization was demonstrated. Cancer cell lines were able to adopt an in vivo tumor-like behavior, endothelial cells reconstituted a vascular-like structure and mesenchymal stem cells adopted a specific organization which can open perspectives for their use and conservation. These results show that our membranes with controllable dual pore architecture offer great potentialities in tissue and tumor engineering.