Characterizing the Macrophage Response to Immunomodulatory Biomaterials Through Gene Set Analyses

Assessing the response of human primary macrophages to defined fibrous architectures fabricated by melt electrowriting

“…Another reason for the mild differences among phenotypes may be the removal of polarizing cytokines during macrophage culture on scaffolds, although we verified by flow cytometry that, after 3 days of culture without cytokines, unpolarized and polarized macrophages maintain distinct phenotypes, with M1 macrophages being characterized by low levels of CD206 and CD163, that are instead highly expressed in M2a and M2c macrophages, respectively. Differently from similar studies that focus on the biomaterial-induced response of unpolarized macrophages [ 26 , 59 , 60 ], here the rationale for evaluating also the response of pre-polarized macrophages was to emulate an implantation scenario where a scaffold is introduced into a region that is potentially exhibiting different inflammatory conditions. Under this scenario, monocytes/macrophages could potentially be already polarized in response to the local signaling events resulting from either the existing condition that necessitates an implant or the implantation procedure itself.…”

Immunomodulation of Acellular Dermal Matrix Through Interleukin 4 Enhances Vascular Infiltration

“…We have demonstrated that ADM used as a delivery device for adsorbed IL-4 significantly increased angiogenesis in a murine dorsal skin fold window chamber model of implant-based breast reconstruction. Interleukin 4 is known to modulate M2 macrophage activity, which is critical for the maturation and stabilization of newly forming vascular networks 20–23,29 . The ability to orderly coordinate the transition to M2 phenotypic profile and accelerate ADM incorporation using ADM as an IL-4 delivery vehicle could improve clinical outcomes and limit dollars lost to complications, even in patients requiring adjunctive radiation.…”

“…Interleukin 4 is known to modulate M2 macrophage activity, which is critical for the maturation and stabilization of newly forming vascular networks. [20][21][22][23]29 The ability to orderly coordinate the transition to M2 phenotypic profile and accelerate ADM incorporation using ADM as an IL-4 delivery vehicle could improve clinical outcomes and limit dollars lost to complications, even in patients requiring adjunctive radiation. This study demonstrated increased vascular integration and maturation within ADM during integration as a function of IL-4 delivery.…”

“…20 Tissue vascularization requires M1 and M2 macrophage activation in the proper sequence, and interleukin 4 (IL-4) is known to modulate M2-driven maturation and stabilization of newly forming and remodeling vascular networks. [20][21][22][23] Some studies have shown that controlled release of IL-4 from biomaterials can improve integration with surrounding tissue, 24 but the effects on vascularization have not been described. The purpose of this study was to investigate whether controlled release of IL-4 from ADM would affect ADM integration and vascularization through the action of host macrophages.…”