Effects of a bioengineered allogeneic cellular construct on burn-related macrophage phenotype

Area of Science:

• Biomaterials Science
• Immunology
• Wound Healing Research

Background:

• Bioengineered allogeneic cellularised constructs (BACC) show pro-healing effects in burn wounds.
• The capacity of BACC to modulate dysregulated macrophages in burn wounds remains unclear.

Purpose of the Study:

• To investigate the ability of BACC to modulate the phenotype of M2b macrophages, an immunosuppressive phenotype relevant to burn wounds.
• To assess the impact of BACC on macrophage gene expression and cytokine secretion in the presence of lipopolysaccharide (LPS).

Main Methods:

• Primary human macrophages were polarized to the M2b phenotype using immunoglobulin G and LPS.
• M2b macrophages were co-cultured with BACC with or without LPS for 1, 3, or 5 days.
• Macrophage gene expression and secretion of tumor necrosis factor α (TNFα) and CCL1 were analyzed.

Main Results:

• BACC upregulated reparative genes and downregulated pro-inflammatory genes in M2b macrophages, even with LPS present.
• Macrophages co-cultured with BACC showed signs of endotoxin tolerance but maintained upregulated reparative genes.
• BACC did not prevent endotoxin tolerance but promoted a reparative phenotype in chronically LPS-exposed macrophages.

Conclusions:

• BACC can promote a reparative phenotype in dysregulated macrophages relevant to burn wound pathophysiology.
• BACC demonstrates potential for therapeutic application in managing burn wound complications involving macrophage dysfunction.