Neonatal Fibrin Scaffolds Promote Enhanced Cell Adhesion, Migration, and Wound Healing In Vivo Compared to Adult Fibrin Scaffolds
Neonatal Fibrin Scaffolds Promote Enhanced Cell Adhesion, Migration, and Wound Healing In Vivo Compared to Adult Fibrin Scaffolds
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DOI：
10.1007/s12195-020-00620-5
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发表时间：
2020-05-27
影响因子：
2.8
通讯作者：
Brown, Ashley C.
中科院分区：
文献类型：
--
作者：
Nellenbach, Kimberly;Nandi, Seema;Brown, Ashley C.
引言柔性支架通常用于治疗慢性伤口。用于产生这种支架的单体纤维蛋白原通常来源于成年人或猪血浆。然而，我们以前的研究已经确定了成人和新生儿之间纤维蛋白网络特性的广泛差异，包括新生儿网络中更高的纤维排列。伤口愈合结果与纤维蛋白基质结构有关，包括纤维排列，这可能影响细胞的结合和迁移。我们假设，与成人纤维蛋白支架相比，新生儿纤维蛋白衍生的纤维蛋白支架将增强伤口愈合结果。方法以纯化的成人或新生儿纤维蛋白原和凝血酶为原料制备成纤维蛋白支架，通过共聚焦显微镜进行结构分析。评估了人新生真皮成纤维细胞在纤维蛋白支架上的附着、迁移和形态。使用鼠全层损伤模型来比较在新生儿纤维蛋白、成人纤维蛋白或盐水存在下的体内愈合。结果在成人和新生儿支架中观察到不同的纤维蛋白结构。与成人相比，在新生儿支架上观察到显著更高的成纤维细胞附着和迁移。新生儿支架上的细胞形态表现出更高的蔓延相比，成人支架。在体内，与成人纤维蛋白或生理盐水对照相比，用新生儿纤维蛋白处理伤口时，观察到伤口面积显著更小，表皮厚度更大。结论新生和成人纤维蛋白支架特性的差异影响细胞行为和伤口愈合。这些研究表明，与源自成人血浆的支架相比，源自新生儿血浆的纤维蛋白支架可以改善愈合结果。
Introduction Fibrin scaffolds are often utilized to treat chronic wounds. The monomer fibrinogen used to create such scaffolds is typically derived from adult human or porcine plasma. However, our previous studies have identified extensive differences in fibrin network properties between adults and neonates, including higher fiber alignment in neonatal networks. Wound healing outcomes have been linked to fibrin matrix structure, including fiber alignment, which can affect the binding and migration of cells. We hypothesized that fibrin scaffolds derived from neonatal fibrin would enhance wound healing outcomes compared to adult fibrin scaffolds. Methods Fibrin scaffolds were formed from purified adult or neonatal fibrinogen and thrombin then structural analysis was conducted via confocal microscopy. Human neonatal dermal fibroblast attachment, migration, and morphology on fibrin scaffolds were assessed. A murine full thickness injury model was used to compare healing in vivo in the presence of neonatal fibrin, adult fibrin, or saline. Results Distinct fibrin architectures were observed between adult and neonatal scaffolds. Significantly higher fibroblast attachment and migration was observed on neonatal scaffolds compared to adults. Cell morphology on neonatal scaffolds exhibited higher spreading compared to adult scaffolds. In vivo significantly smaller wound areas and greater epidermal thickness were observed when wounds were treated with neonatal fibrin compared to adult fibrin or a saline control. Conclusions Distinctions in neonatal and adult fibrin scaffold properties influence cellular behavior and wound healing. These studies indicate that fibrin scaffolds sourced from neonatal plasma could improve healing outcomes compared to scaffolds sourced from adult plasma.