Bioactive nanoparticle-based formulations increase survival area of perforator flaps in a rat model

BACKGROUND: Distal flap necrosis is a frequent complication of perforator flaps. Advances in nanotechnology offer exciting new therapeutic approaches. Anti-inflammatory and neo-angiogenic properties of certain metal oxides within the nanoparticles, including bioglass and ceria, may promote flap survival. Here, we explore the ability of various nanoparticle formulations to increase flap survival in a rat model. MATERIALS AND METHODS: A 9 x 3 cm dorsal flap based on the posterior thigh perforator was raised in 32 Lewis rats. They were divided in 4 groups and treated with different nanoparticle suspensions: I–saline (control), II–Bioglass, III–Bioglass/ceria and IV–Zinc-doped strontium-substituted bioglass/ceria. On post-operative day 7, planimetry and laser Doppler analysis were performed to assess flap survival and various samples were collected to investigate angiogenesis, inflammation and toxicity. RESULTS: All nanoparticle-treated groups showed a larger flap survival area as compared to the control group (69.9%), with groups IV (77,3%) and II (76%) achieving statistical significance. Blood flow measurements by laser Doppler analysis showed higher perfusion in the nanoparticle-treated flaps. Tissue analysis revealed higher number of blood vessels and increased VEGF expression in groups II and III. The cytokines CD31 and MCP-1 were decreased in groups II and IV. CONCLUSIONS: Bioglass-based nanoparticles exert local anti-inflammatory and neo-angiogenic effects on the distal part of a perforator flap, increasing therefore its survival. Substitutions in the bioglass matrix and trace metal doping allow for further tuning of regenerative activity. These results showcase the potential utility of these nanoparticles in the clinical setting.