Biocompatible surfaces and optimized angiogenesis, aiming at the development of vascularized biohybrid organs

Biohybrid organs are limited in size by the lack of a vascular network, which could be overcome by a network produced by two-photon polymerization. The lumina of these networks could be coated with endothelial cells. In this context, macrophages are relevant, because they mediate foreign body reactions and can support the formation of blood vessels. Macrophages form a continuum of different phenotypes with pro-inflammatory M1 and anti-inflammatory M2 macrophages being the extremes. The first aim of this study was to assess the biocompatibility of the printing resins IP-Visio and IP-S. The second aim was to investigate the potential of macrophages derived from a monocytic cell line to foster blood vessel formation.
M1-like macrophages were differentiated out of THP-1 cells and cultured on printed IP-Visio and IP-S in the absence or presence of appropriate stimuli that induce the release of the pro-inflammatory cytokines, interleukin (IL)-1β and IL-6. Before performing tube formation assays, these assays were simulated using M0-, M1-, and M2-like THP-1-derived macrophages to assess potential changes. Thereafter, tube formation assays were performed using endothelial cells in co-culture with macrophages.
M1-like macrophages released cytokines in response to appropriate stimuli. IP-Visio or IP-S did not further stimulate cytokine release. The resins allowed for a proper adhesion of macrophages and did not induce cell death. Simulation of tube formation assays in a medium compatible with the culture of macrophages led to subtle changes in cell surface marker expression and to a reduction of the cytokine release by M1-like macrophages, while that of M2-like macrophages increased. The cytokine release was drastically reduced when macrophages were cultured in endothelial cell culture media. M1- and M2-like macrophages only improved the results of the tube formation assays, when the co-culture was performed in a medium typically used with macrophages.
The results of this study are consistent with the assumption that IP-Visio and IP-S are cytocompatible and do not provoke inflammation, making them promising materials for vascular network printing. No firm conclusions can be drawn from the tube formation assays. Additional research is needed to decide if THP-1 cell-derived macrophages can promote the vascularization in engineered tissues.