LAUSR

Tissue regeneration evolves towards 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, appear as ideal methods to modulate the immune response. However, the interplay between these properties is yet not clear. We created dual-porosity scaffolds with varying mechanical and topographical features and evaluated their immunomodulatory properties in rat alveolar macrophages in vitro, and in vivo in a rat subcutaneous model. Scaffolds were fabricated via additive-manufacturing and thermally induced phase separation (TIPS) methods from two copolymers with virtually identical chemistries, but different stiffness. The introduction of porosity enabled the modulation of macrophages towards anti-inflammatory phenotypes, with secretion of IL-10 and TGF-β. Soft scaffolds (< 5 kPa) resulted in a pro-inflammatory phenotype in contrast to stiffer (> 40 kPa) scaffolds of comparable porosities supporting a pro-healing phenotype, which appeared to be related to the surface spread area of cells. In vivo, stiff scaffolds integrated, while softer scaffolds appeared encapsulated after 3 weeks of implantation, resulting on chronic inflammation after 6 weeks. Our results demonstrate the importance of evaluating the interplay between topography and stiffness of candidate scaffolds. This article is protected by copyright. All rights reserved.