Park Chan J, Clark Sherrie G, Lichtensteiger Carol A, Jamison Russell D, Johnson Amy J Wagoner
Department of Materials Science & Engineering, University of Illinois at Urbana-Champaign, 61801, USA.
Acta Biomater. 2009 Jul;5(6):1926-36. doi: 10.1016/j.actbio.2009.03.002. Epub 2009 Mar 11.
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.
压疮是一个重大的医疗保健问题,尤其对于老年人群体。我们的工作旨在通过解决由中性粒细胞介导的缺血再灌注损伤以及这些伤口中随之而来的血管丧失,来改善这些溃疡的慢性状况。为此,开发了负载明胶微粒中所含碱性成纤维细胞生长因子(bFGF)的壳聚糖支架,并在老年小鼠模型中测试其临床相关性。在老年小鼠中诱导形成压疮,并评估治疗效果。在第3天和第7天,与纱布对照相比,壳聚糖和壳聚糖 - bFGF支架均显著加速了伤口愈合。到第10天,所有伤口均实现了相似程度的愈合。通过酶联免疫吸附测定(ELISA)和组织学验证了bFGF的递送和血管生成功能。在壳聚糖和壳聚糖 - bFGF组中观察到中性粒细胞水平升高。由于中性粒细胞弹性蛋白酶促成了压疮的蛋白水解环境,因此评估了壳聚糖对弹性蛋白酶的影响。在体外,壳聚糖抑制弹性蛋白酶活性。在体内,到第10天时,壳聚糖 - bFGF支架使伤口中的弹性蛋白酶蛋白水平降低。这些结果表明,壳聚糖是一种用于生长因子递送的有效材料,并且有助于治愈慢性溃疡。总体而言,我们的数据表明壳聚糖 - bFGF支架在加速老年动物压疮伤口愈合方面是有效的。