3D Printed Dual-Porosity Scaffolds: The Combined Effect of Stiffness and Porosity in the Modulation of Macrophage Polarization


Tissue regeneration evolves toward the biofabrication of sophisticated 3D scaffolds. However, the success of these will be contingent to their capability to integrate within the host. The control of the mechanical or topographical properties of the implant appears as an ideal method to modulate the immune response. However, the interplay between these properties is yet not clear. Dual-porosity scaffolds with varying mechanical and topographical features are created, and their immunomodulatory properties in rat alveolar macrophages in vitro and in vivo in a rat subcutaneous model are evaluated. Scaffolds are fabricated via additive manufacturing and thermally induced phase separation methods from two copolymers with virtually identical chemistries, but different stiffness. The introduction of porosity enables the modulation of macrophages toward anti-inflammatory phenotypes, with secretion of IL-10 and TGF-beta. Soft scaffolds (<5 kPa) result in a pro-inflammatory phenotype in contrast to stiffer (>40 kPa) scaffolds of comparable porosities supporting a pro-healing phenotype, which appears to be related to the surface spread area of cells. In vivo, stiff scaffolds integrate, while softer scaffolds appear encapsulated after three weeks of implantation, resulting in chronic inflammation after six weeks. The results demonstrate the importance of evaluating the interplay between topography and stiffness of candidate scaffolds.



subject category

Engineering; Science & Technology - Other Topics; Materials Science


Camarero-Espinosa, S; Carlos-Oliveira, M; Liu, H; Mano, JF; Bouvy, N; Moroni, L

our authors


This work was supported by the ERC starting grant Cell Hybridge under the Horizon2020 framework program (Grant No. 637308). S.C.E. acknowledges the supported by the Marie-Slodowska-Curie Action PRIUSTE under the H2020 framework program [845488]. J.F.M. acknowledges the support from the projects CICECO-Aveiro Institute of Materials (UIDB/50011/2020 and UIDP/50011/2020), financed from the Foundation for Science and Technology/MCTES. The authors are grateful to Andrea Calore for helping with microCT analysis and to Marloes Peters and David Koper for support during the animal experiments.

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