In vitro and in vivo evaluation of the inflammatory response to nanoscale grooved substrates

The immune response to an implanted biomaterial is orchestrated by macrophages. In this study various nanogrooved patterns were created by using laser interference lithography and reactive ion etching. The created nanogrooves mimic the natural extracellular matrix environment. Macrophage cell culture demonstrated that interleukin 1β and TNF-α cytokine production were upregulated on nanogrooved substrates. In vivo subcutaneous implantation in a validated mouse cage model for 14 days demonstrated that nanogrooves enhanced and guided cell adhesion, and few multinucleated cells were formed. In agreement with the in vitro results, cytokine production was found to be nanogroove dependent, as interleukin 1β, TNF-α, TGF-β and osteopontin became upregulated. The results indicate that biomaterial surface texturing, especially at the nanometric scale, can be used to control macrophage activation to induce a wound healing response, rather than a profound inflammatory response.From the Clinical EditorThe authors investigate various nano-grooved patterns that mimic the natural extracellular matrix environment and demonstrate (both in macrophage cultures and in vivo) that interleukin 1β and TNF-α cytokine production is dependent upon surface texturing at the nanometric scale. They propose that modified surfaces may trigger macrophage activation to promote a wound healing response.

Graphical AbstractThe inflammatory response to nanogrooved substrates was first analyzed in vitro and subsequently the in vivo inflammatory response was determined. Results from both the in vitro and in vivo evaluation demonstrated that nanogrooves induced an altered immune response: Cells were aligned to grooves down to 300 nm pitch and cytokine production was texture dependent. In vitro analysis demonstrated that after 3 days on all substrates, many multinucleated cells were observed (asterisks). In vivo analysis revealed that the lowest density of multinucleated cells was observed on grooves with a 150 nm pitch.Figure optionsDownload high-quality image (162 K)Download as PowerPoint slide