Nellenbach Kimberly, Nandi Seema, Peeler Christopher, Kyu Alexander, Brown Ashley C
Joint Department of Biomedical Engineering, North Carolina State University and The University of North Carolina at Chapel Hill, Raleigh, NC 27695 USA.
Comparative Medicine Institute, North Carolina State University, Raleigh, NC 27695 USA.
Cell Mol Bioeng. 2020 May 27;13(5):393-404. doi: 10.1007/s12195-020-00620-5. eCollection 2020 Oct.
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.
Fibrin scaffolds were formed from purified adult or neonatal fibrinogen and thrombin then structural analysis was conducted 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 the presence of neonatal fibrin, adult fibrin, or saline.
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. 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.
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.
纤维蛋白支架常用于治疗慢性伤口。用于制造此类支架的单体纤维蛋白原通常来源于成人或猪的血浆。然而,我们之前的研究发现成人和新生儿的纤维蛋白网络特性存在广泛差异,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,这会影响细胞的黏附和迁移。我们假设,与成人纤维蛋白支架相比,源自新生儿纤维蛋白的纤维蛋白支架将改善伤口愈合结果。
由纯化的成人或新生儿纤维蛋白原和凝血酶形成纤维蛋白支架,然后通过共聚焦显微镜进行结构分析。评估人新生儿真皮成纤维细胞在纤维蛋白支架上的黏附、迁移和形态。使用小鼠全层损伤模型比较在存在新生儿纤维蛋白、成人纤维蛋白或生理盐水的情况下的愈合情况。
在成人和新生儿支架之间观察到不同的纤维蛋白结构。与成人支架相比,在新生儿支架上观察到成纤维细胞的黏附和迁移明显更高。与成人支架相比,新生儿支架上的细胞形态表现出更高的铺展。与成人纤维蛋白或生理盐水对照相比,用新生儿纤维蛋白治疗伤口时观察到伤口面积明显更小,表皮厚度更大。
新生儿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。