Protease-Resistant Growth Factor Formulations for the Healing of Chronic Wounds.
Protease-Resistant Growth Factor Formulations for the Healing of Chronic Wounds.
复制标题
用于治愈慢性伤口的蛋白酶抗性生长因子制剂。
DOI：
10.1089/wound.2019.1043
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发表时间：
2020
影响因子：
4.9
通讯作者：
Koria,Piyush
中科院分区：
文献类型：
--
作者：
Boeringer,Tabitha;Gould,LisaJ;Koria,Piyush
目的：慢性伤口是难以治疗的长期不愈合伤口。这些伤口可能会出现蛋白酶水平升高，导致天然和外源添加的生长因子快速降解。这项工作的重点是开发一种抗蛋白酶生长因子制剂，用于治疗具有高蛋白酶活性的慢性伤口。 方法：本研究开发了一种抗蛋白酶生长因子制剂，其中包含与已知的蛋白酶抑制剂肽或生长因子融合的类弹性蛋白肽 (ELP)。融合蛋白的 ELP 成分允许组装异质纳米颗粒 (NP)，使抑制剂靠近要保护的生长因子。结果：我们在高人中性粒细胞弹性蛋白酶 (HNE) 环境和源自患者的人慢性伤口液中成功保留了生长因子活性。我们进一步表明，在遗传性糖尿病小鼠中补充 HNE 的全层伤口中，这些 NP 可以增强胶原蛋白重塑和炎症消退。创新：开发异质 NP，将蛋白酶抑制剂置于生长因子附近。此外，纳米颗粒的模块化性质允许通过同一抑制剂保护多种生长因子，而不改变生长因子的氨基酸序列。结论：我们的结果表明，所开发的纳米颗粒在慢性伤口愈合治疗中具有巨大的前景，并可能进一步帮助生长因子疗法转化为临床。 NP 设计的可定制模板允许在研究和医学的多个领域进行多方面的使用。
Objective:Chronic wounds are long-term nonhealing wounds that are refractory to treatment. These wounds can present elevated protease levels, leading to rapid degradation of native and exogenously added growth factors. This work focused on developing a protease-resistant growth factor formulation for treatment of chronic wounds presented with high protease activity.Approach:This study developed protease-resistant growth factor formulations comprising elastin-like peptides (ELPs) fused with a known protease inhibitor peptide or growth factor. The ELP component of the fusion proteins allows assembly of heterogeneous nanoparticles (NPs) putting the inhibitor in close proximity to the growth factor to be protected.Results:We show successful preservation of growth factor activity in high human neutrophil elastase (HNE) environment and in human chronic wound fluid derived from patients. We further show that these NPs result in enhanced collagen remodeling and resolution of inflammation in a full thickness wound supplemented with HNE in genetically diabetic mice.Innovation:Development of heterogeneous NPs that put the protease inhibitor in close proximity of the growth factor. Moreover, the modular nature of the NPs allows for protection of multiple growth factors by the same inhibitor without changing the amino acid sequence of the growth factor.Conclusion:Our results indicate that the developed NPs hold tremendous promise in chronic wound healing therapy and may further help the translation of growth factor therapies to clinic. The customizable template for the NP design allows for multifaceted use across several fields in research and medicine.