Stabilized Interleukin-4-Loaded Poly(lactic-co-glycolic) Acid Films Shift Proinflammatory Macrophages toward a Regenerative Phenotype in Vitro

• Published in: ACS applied bio materials Vol. 2; no. 4; pp. 1498 - 1508
• Main Authors: Ziemba, Alexis M, D’Amato, Anthony R, MacEwen, Taylor M, Puhl, Devan L, Koppes, Abigail N, Koppes, Ryan A, Lennartz, Michelle R, Gilbert, Ryan J
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 15-04-2019
• Subjects: interleukin-4; macrophage; poly(lactic-co-glycolic acid); inflammation; cytokine stabilization
• ISSN: 2576-6422; 2576-6422
• DOI: 10.1021/acsabm.8b00769

Macrophages are immune cells involved in wound healing and tissue regeneration; however, the sustained presence of proinflammatory macrophages in wound sites impairs healing. In this study, we shifted peritoneal macrophage polarization away from a proinflammatory (M1) phenotype through exposure to stabilized interleukin-4 (IL-4) in poly­(lactic-co-glycolic acid) films in combination with topographical guidance from electrospun poly-l-lactic acid fibers. To our knowledge, this was the first study to stabilize IL-4 with bovine serum albumin (BSA) within a biomaterial. When IL-4 was coloaded with BSA for stabilization, we saw increased IL-4 bioactivity compared to no added stabilization, trehalose stabilization, or murine serum albumin stabilization. We observed increased elongation of peritoneal macrophages, increased RNA expression of anti-inflammatory marker arginase-1, increased ratio of interleukin-10/interleukin-12 p40 RNA, and decreased protein expression of proinflammatory markers (interleukin-12 p40 and RANTES) compared to controls. Taken together, these results suggest the macrophages were less proinflammatory and were a more pro-resolving phenotype. When stabilized with BSA, IL-4-loaded films effectively shift macrophage polarization state and are thus promising scaffolds to reduce inflammation within in vivo injury models.