Self-assembling elastin-like peptides growth factor chimeric nanoparticles for the treatment of chronic wounds
Self-assembling elastin-like peptides growth factor chimeric nanoparticles for the treatment of chronic wounds
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DOI：
10.1073/pnas.1009881108
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发表时间：
2011-01-18
影响因子：
11.1
通讯作者：
Yarmush, Martin L.
中科院分区：
文献类型：
--
作者：
Koria, Piyush;Yagi, Hiroshi;Yarmush, Martin L.
慢性伤口与差的表皮和真皮重塑相关。先前的工作已经显示了角质形成细胞生长因子（KGF）在表皮再生和弹性蛋白在皮肤伤口愈合中的功效。在这里，我们展示了弹性蛋白样肽和KGF的融合蛋白的制造。这种融合蛋白保留了KGF和弹性蛋白的性能特征，如其增强角质形成细胞和成纤维细胞增殖所证明的。它还保留了弹性蛋白样肽的特征性反相转变，使重组蛋白能够在细菌宿主（例如大肠杆菌）中表达，并使用逆温度循环快速轻松地纯化。融合蛋白在生理温度下自组装成纳米颗粒。当应用于Lepr（db）糖尿病小鼠的全层伤口时，与对照相比，这些颗粒分别增强了2倍和3倍的上皮再生和肉芽形成。这些数据强烈表明，这些自组装纳米颗粒可能有利于治疗糖尿病或其他潜在循环疾病引起的慢性伤口。
Chronic wounds are associated with poor epidermal and dermal remodeling. Previous work has shown the efficacy of keratinocyte growth factor (KGF) in reepithelialization and elastin in dermal wound healing. Here we demonstrate the fabrication of a fusion protein comprising of elastin-like peptides and KGF. This fusion protein retains the performance characteristics of KGF and elastin as evidenced by its enhancement of keratinocyte and fibroblast proliferation. It also preserved the characteristic elastin-like peptides inverse phase transitioning allowing the recombinant protein to be expressed in bacterial hosts (such as Escherichia coli) and purified rapidly and easily using inverse temperature cycling. The fusion protein self-assembled into nanoparticles at physiological temperatures. When applied to full thickness, wounds in Lepr(db) diabetic mice these particles enhanced reepithelialization and granulation, by 2- and 3-fold respectively, when compared to the controls. The data strongly suggests that these self-assembled nanoparticles may be beneficial in the treatment of chronic wounds resulting from diabetes or other underlying circulatory conditions.