Translation of Collagen Ultrastructure to Biomaterial Fabrication for Material‐Independent but Highly Efficient Topographic Immunomodulation. Issue 33 (8th July 2021)

• Record Type: Journal Article
• Authors: Ryma, Matthias; Tylek, Tina; Liebscher, Julia; Blum, Carina; Fernandez, Robin; Böhm, Christoph; Kastenmüller, Wolfgang; Gasteiger, Georg; Groll, Jürgen
• Is Part Of: Advanced materials. Volume 33:Issue 33(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-07-08
• Subjects: biofabrication -- extracellular matrix -- immunomodulation -- macrophages -- melt electrofibrillation -- melt electrowriting; Materials -- Periodicals; Chemical vapor deposition -- Periodicals; 620.11
• DOI: 10.1002/adma.202101228
• Languages: English
• ISSNs: 0935-9648

Abstract

Abstract: Supplement‐free induction of cellular differentiation and polarization solely through the topography of materials is an auspicious strategy but has so far significantly lagged behind the efficiency and intensity of media‐supplementation‐based protocols. Consistent with the idea that 3D structural motifs in the extracellular matrix possess immunomodulatory capacity as part of the natural healing process, it is found in this study that human‐monocyte‐derived macrophages show a strong M2a‐like prohealing polarization when cultured on type I rat‐tail collagen fibers but not on collagen I films. Therefore, it is hypothesized that highly aligned nanofibrils also of synthetic polymers, if packed into larger bundles in 3D topographical biomimetic similarity to native collagen I, would induce a localized macrophage polarization. For the automated fabrication of such bundles in a 3D printing manner, the strategy of "melt electrofibrillation" is pioneered by the integration of flow‐directed polymer phase separation into melt electrowriting and subsequent selective dissolution of the matrix polymer postprocessing. This process yields nanofiber bundles with a remarkable structural similarity to native collagen I fibers, particularly for medical‐grade poly(ε‐caprolactone). These biomimetic fibrillar structures indeed induce a pronounced elongation of human‐monocyte‐derived macrophages and unprecedentedly trigger their M2‐like polarization similar in efficacy as interleukin‐4 treatment. Abstract : Collagen I fibrils are found to exhibit unprecedented topographic immunomodulatory effects on human macrophages equal in intensity to the established interleukin‐4‐based biochemical induction. Employing melt electrofibrillation, a printing technique that allows the fabrication of collagen‐fibril‐mimetic nanofibrillar microbundles, it is demonstrated that this strong immunomodulatory effect is purely topographic and can be translated to synthetic materials.