Accelerated wound closure of pressure ulcers in aged mice by chitosan scaffolds with and without bFGF

Abstract

Pressure ulcers are a significant healthcare concern, especially for elderly populations. Our work served to ameliorate the chronicity of these ulcers by addressing ischemia–reperfusion injury mediated by neutrophils and the concomitant loss of vasculature in these wounds. To this end, chitosan scaffolds loaded with basic fibroblast growth factor (bFGF) contained in gelatin microparticles were developed and tested for clinical relevance in an aged mouse model. Pressure ulcers were induced in aged mice, and efficacy of treatment was assessed. On days 3 and 7, both chitosan and chitosan–bFGF scaffolds significantly accelerated wound closure compared to gauze control. By day 10, all wounds achieved similar closure. Delivery and angiogenic function of bFGF was verified through ELISA and histology. Elevated neutrophil levels were observed in chitosan and chitosan–bFGF groups. Since neutrophil elastase contributes to the proteolytic environments of pressure ulcers, the effect of chitosan on elastase was assessed. In vitro, chitosan inhibited elastase activity. In vivo, elastase protein levels in wounds were reduced with chitosan–bFGF scaffolds by day 10. These results suggest that chitosan is an effective material for growth factor delivery and can help to heal chronic ulcers. Collectively, our data show that chitosan–bFGF scaffolds are effective in accelerating wound closure of pressure ulcers in aged animals.