Protein Adsorption on Surfaces Functionalized with COOH Groups Promotes Anti-inflammatory Macrophage Responses

Implants can induce a foreign body
reaction that leads to chronic
inflammation and fibrosis in the surrounding tissue. Macrophages help
detect the foreign material, play a role in the inflammatory response,
and may promote fibrosis instead of the desired tissue regeneration
around implants. Implant surface properties impact macrophage responses
by changing the nature of the adsorbed protein layer, but conflicting
studies highlight the complexity of this relationship. In this study,
the effect of surface chemistry on macrophage behavior was investigated
with poly­(styrene) surfaces containing common functional groups at
similar surface densities. The protein layer was characterized to
identify the proteins that adsorbed on the surfaces from the medium
and the proteins secreted onto the surfaces by adherent macrophages.
Of the surface chemistries studied, carboxylic acid (COOH) groups
promoted anti-inflammatory responses from unstimulated macrophages
and did not exacerbate inflammation upon stimulation. These surfaces
also enhanced the adsorption of proteins involved in integrin signaling
and promoted the secretion of proteins related to angiogenesis, integrin
signaling, and cytokine signaling, which have been previously associated
with improved biomaterial integration. Therefore, this study suggests
that surface modification with COOH groups may help improve the integration
of implants in the body by enhancing anti-inflammatory macrophage
responses through altered protein adsorption.