2023 journal article

Heparin Affinity-Based IL-4 Delivery to Modulate Macrophage Phenotype and Endothelial Cell Activity In Vitro

ACS APPLIED MATERIALS & INTERFACES, 15(23), 27457–27470.

By: F. Zhang n, J. Gluck n, A. Brown n, D. Zaharoff n & M. King n

author keywords: gelatin methacryloyl; heparin; interleukin4; hydrogel; macrophage; endothelial cell; immunomodulation
MeSH headings : Interleukin-4 / pharmacology; Heparin / pharmacology; Heparin / metabolism; Macrophages / metabolism; Phenotype; Hydrogels / pharmacology; Hydrogels / metabolism
TL;DR: A gelatin-heparin-methacrylate hydrogel is engineered that gradually releases interleukin-4 (IL-4), a cytokine that modulates macrophages to adopt the M2 phenotype and synergistically downregulated M1 gene expression and upregulated M2 gene expression within 48 h of in vitro cell culture. (via Semantic Scholar)
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Source: Web Of Science
Added: June 26, 2023

Macrophages play a pivotal role in wound healing and tissue regeneration, as they are rapidly recruited to the site of injury or implanted foreign material. Depending on their interaction with the material, macrophages can develop different phenotypes, with the M1 pro-inflammatory and M2 pro-regenerative phenotypes being highly involved in tissue regeneration. M2 macrophages mitigate inflammation and promote tissue regeneration and extracellular matrix remodeling. In this study, we engineered a gelatin-heparin-methacrylate (GelMA-HepMA) hydrogel that gradually releases interleukin-4 (IL-4), a cytokine that modulates macrophages to adopt the M2 phenotype. Methacrylation of heparin improved the retention of both heparin and IL-4 within the hydrogel. The GelMA-HepMA hydrogel and IL-4 synergistically downregulated M1 gene expression and upregulated M2 gene expression in macrophages within 48 h of in vitro cell culture. However, the M2-like macrophage phenotype induced by the GelMA-HepMA-IL-4 hydrogel did not necessarily further improve endothelial cell proliferation and migration in vitro.