Effects of substrate topography on the regulation of human fibroblasts and capsule formation via modulating macrophage polarization

The host-material interface is critical in determining the successful integration of medical devices into human tissue. The surface topography can regulate the fibrous capsule formation around implants through macrophage polarization, but the exact mechanism remains unclear. In this study, four types of microgrooves (10 or 50 µm in groove depths and 50 or 200 µm in groove widths) were fabricated on polydimethylsiloxane (PDMS) using lithography. The microgroove surfaces were characterized using the laser scanning confocal microscopy and fourier transform infrared spectroscopy. The effect of surface topography on macrophage phenotypes and conditioned medium (CM) collected from macrophages on human foreskin fibroblast 1 (HFF-1) were investigated. The result revealed that a deeper and narrower microgroove structure means a rougher surface. Macrophages tended to adhere and aggregate on group 50–50 surface (groove depths and widths of 50 µm). THP-1 cell polarized toward both inflammatory M1 and anti-inflammatory M2 macrophages on the surface of each group. Meanwhile, CM from macrophages culture on PDMS differentially up-regulated the proliferation, migration and fibrosis of HFF-1. Among them, the group 50–50 had the strongest promoting effect. In vivo, the inflammatory response and fibrotic capsule around the implants were observed at 1 week and 4 weeks. As time passed, the inflammatory response decreased, while the capsule thickness continued to increase. The rough material surface was more inclined to develop a severe fibrotic encapsulation. In conclusion, this finding further suggested a potential immunomodulatory effect of macrophages in mediating the fibrotic response to implants and facilitated the design of biomaterial interfaces for improving tissue integration. [Display omitted] •Construct specific geometric patterns to realize material surface bionic topologies.•Reveal the role of roughness in regulating inflammation and capsule formation.•Confirm the potential immunomodulatory effect of macrophages in fibrotic process.•Facilitate the design of biomaterial interfaces for improving tissue integration.