Curcumin-loaded alkali-heat-treated titanium modulates macrophage inflammatory responses

Chronic inflammation at the implant-tissue interface is a major contributor to implant failure. Therefore, enhancing the biological response of titanium (Ti) surfaces is critical for promoting early osseointegration and improving long-term implant stability. In this study, alkali-heat-treated (AHT) Ti was evaluated as a platform for the controlled delivery of curcumin (Cur), a natural anti-inflammatory compound. The release kinetics of curcumin and the interactions between curcumin-loaded AHT Ti surfaces and RAW264.7 macrophages were investigated in vitro. Various polymer coating strategies were applied to modulate curcumin release. The presence of poly(lactic-co-glycolic acid) (PLGA) reduced the curcumin release under both physiological (pH 7.4) and acidic (pH 5.0) conditions, with uncoated AHT samples exhibiting the greatest cumulative release (∼21.3 μg) in Study 1. Increasing the loaded curcumin amount from 100 to 300 μg resulted in a decrease in the release for both pH 7.4 and pH 5.0, whereas the incorporation of polyethylene glycol/polycaprolactone (PEG/PCL) coating enhanced the gradual curcumin release (Study 2). Increasing the curcumin loading from 50 to 100 and 300 μg increased the total amount of curcumin released, with the 300 μg group exhibiting a more gradual release profile. However, the percentage of curcumin released decreased as the loading amount increased (Study 3). When macrophages were cultured on Ti surfaces, AHT samples exhibited higher cell viability than polished (P) control samples, and the presence of curcumin reduced cell viability in a dose-dependent manner. While macrophages cultured on AHT surfaces exhibited a transient increase in pro-inflammatory marker expression at 24 h compared with polished surfaces, the expression of these markers was reduced by 48 h. Notably, curcumin significantly decreased pro-inflammatory cytokine expression at both the gene and protein levels and suppressed NF-κB activation in macrophages exposed to inflammatory stimuli. Overall, the sustained and controlled release of curcumin from AHT Ti surface is highly dependent on the curcumin loading amount as well as the presence and composition of the polymer coating. Moreover, both AHT and curcumin significantly reduced inflammatory responses in macrophages, demonstrating the potential of the curcumin-loaded AHT Ti platform as an immunomodulatory surface for improving the biological performance and long-term success of Ti implants.