The functionality and durability of implanted biomaterials are often compromised by an exaggerated foreign body reaction (FBR). M1/M2 polarization of macrophages is a critical regulator of scaffold-induced FBR. Macrophage colony-stimulating factor (M-CSF), a hematopoietic growth factor, induces macrophages into an M2-like polarized state, leading to immunoregulation and promoting tissue repair. In the present study, we explored the immunomodulatory effects of surface bound M-CSF on poly-L-lactic acid (PLLA)-induced FBR M-CSF was immobilized on the surface of PLLA via plasma immersion ion implantation (PIII). M-CSF functionalized PLLA, PLLA-only, and PLLA+PIII were assessed in an IL-1 beta luciferase reporter mouse to detect real-time levels of IL-1 beta expression, reflecting acute inflammation in vivo. Additionally, these different treated scaffolds were implanted subcutaneously into wild-type mice to explore the effect of M-CSF in polarization of M2-like macrophages (CD684/CD2064), related cytokines (pro-inflammatory: IL-1 beta, TNF and MCP-1; anti-inflammatory: IL-10 and TGF-/3), and angiogenesis (CD31) by immunofluorescent staining. Our data demonstrated that IL-1 beta activity in M-CSF functionalized scaffolds was similar to 50% reduced compared to PLLA-only at day 1 (p < 0.01) and day 2 (p < 0.05) post implantation. There were >2.6-fold more CD206+ macrophages in M-CSF functionalized PLLA compared to PLLA-only at day 7 (p < 0.001), along with higher levels of IL-10 at both day 7 (p < 0.05) and day 14 (p < 0.01), and TGF-/3 at day 3 (p < 0.05), day 7 (p < 0.05), and day 14 (p < 0.001). Lower levels of pro-inflammatory cytokines were also detected in M-CSF functionalized PLLA in the early phase of the immune response compared to PLLA-only: a 58% decrease at day 3 in IL-1 beta; a similar to 91% decrease at day 3 and a similar to 6% decrease at day 7 in TNF; and a similar to 60% decrease at day 7 in MCP-1. Moreover, enhanced angiogenesis inside and on/near the scaffold was observed in M-CSF functionalized PLLA compared to PLLA-only at day 3 (p < 0.05) and day 7 (p < 0.05), respectively. Overall, M-CSF functionalized PLLA enhanced CD206+ macrophage polarization and angiogenesis, consistent with lower levels of pro-inflammatory cytokines and higher levels of anti-inflammatory cytokines in early stages of the host response, indicating potential immunoregulatory functions on the local environment.
基金：
National Health and Medical Research CouncilNational Health and Medical Research Council of Australia [APP1162969]; Australian Postgraduate Scholarships; Heart Research InstituteUniversity of Sydney; Edith Mary Rose travelling fellowship; University of SydneyUniversity of Sydney
第一作者机构：[1]Univ Sydney, Heart Res Inst, Sydney, NSW, Australia[2]Univ Sydney, Sydney, NSW, Australia
通讯作者：
通讯机构：[1]Univ Sydney, Heart Res Inst, Sydney, NSW, Australia[2]Univ Sydney, Sydney, NSW, Australia
推荐引用方式(GB/T 7714)：
Yang Nianji,Tan Richard P.,Chan Alex H. P.,et al.Immobilized Macrophage Colony-Stimulating Factor (M-CSF) Regulates the Foreign Body Response to Implanted Materials[J].ACS BIOMATERIALS SCIENCE & ENGINEERING.2020,6(2):995-1007.doi:10.1021/acsbiomaterials.9b01887.
APA：
Yang, Nianji,Tan, Richard P.,Chan, Alex H. P.,Lee, Bob S. L.,Santos, Miguel...&Bao, Shisan.(2020).Immobilized Macrophage Colony-Stimulating Factor (M-CSF) Regulates the Foreign Body Response to Implanted Materials.ACS BIOMATERIALS SCIENCE & ENGINEERING,6,(2)
MLA：
Yang, Nianji,et al."Immobilized Macrophage Colony-Stimulating Factor (M-CSF) Regulates the Foreign Body Response to Implanted Materials".ACS BIOMATERIALS SCIENCE & ENGINEERING 6..2(2020):995-1007
