Journal
ACS APPLIED BIO MATERIALS
Volume 2, Issue 4, Pages 1498-1508Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsabm.8b00769
Keywords
macrophage; inflammation; interleukin-4; poly(lactic-co-glycolic acid); cytokine stabilization
Funding
- NSF CAREER Award (BMAT) [1150125]
- NY State Spinal Cord Injury Grant [C32245GG]
- National Science Foundation Graduate Research Fellowship Program [DGE-1247271]
- Department of Chemical Engineering at Northeastern University
- NINDS [NS092754]
- Division Of Materials Research
- Direct For Mathematical & Physical Scien [1150125] Funding Source: National Science Foundation
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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.
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