Solvent-free preparation of porous poly(L-lactide) microcarriers for cell culture

Porous polymeric microcarriers are a versatile class of biomaterial constructs with extensive use in drug delivery, cell culture and tissue engineering. Currently, most methods for their production require potentially toxic organic solvents with complex setups which limit their suitability for biomedical applications and their large-scale production. Herein, we report an organic, solvent-free method for the fabrication of porous poly(L-lactide) (PLLA) microcarriers. The method is based on the spherulitic crystallization of PLLA in its miscible blends with poly(ethylene glycol) (PEG). It is shown that the PLLA spherulites are easily recovered as microcarriers from the blends by a water-based process. Independent control over microcarrier size and porosity is demonstrated, with a higher crystallization temperature leading to a larger size, and a higher PLLA content in the starting blend resulting in a lower microcarrier porosity. Microcarriers are shown to be biocompatible for the culture of murine myoblasts and human adipose stromal/stem cells (hASC). Moreover, they support not only the long-term proliferation of both cell types but also hASC differentiation toward osseous tissues. Furthermore, while no significant differences are observed during cell proliferation on microcarriers of two different porosities, microcarriers of lower porosity induce a stronger hASC osteogenic differentiation, as evidenced by higher ALP enzymatic activity and matrix mineralization. Consequently, the proposed organic-solvent-free method for the fabrication of biocompatible porous PLLA microcarriers represents an innovative methodology for ex vivo cell expansion and its application in stem cell therapy and tissue engineering. (C) 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.