Department of Materials Science and Engineering, The Ohio State University, Columbus, OH, United States; Department of Biomedical Engineering, The Ohio State University, Columbus, OH, United States.
Research Department, Shriners Hospitals for Children, Cincinnati, OH, United States.
Acta Biomater. 2018 Oct 15;80:247-257. doi: 10.1016/j.actbio.2018.09.014. Epub 2018 Sep 12.
Engineered skin (ES) offers many advantages over split-thickness skin autografts for the treatment of burn wounds. However, ES, both in vitro and after grafting, is often significantly weaker, less elastic and more compliant than normal human skin. Biomechanical properties of ES can be tuned in vitro using electrospun co-axial (CoA) scaffolds. To explore the potential for coaxial scaffold-based ES use in vivo, two CoA scaffolds were fabricated with bioactive gelatin shells and biodegradable synthetic cores of polylactic acid (PLA) and polycaprolactone (PCL), and compared with gelatin monofilament scaffolds. Fibroblast and macrophage production of inflammatory cytokines interleukin 6 (IL-6) and transforming growth factor β-1 was significantly higher when cultured on PLA and PCL monofilament scaffolds compared to gelatin monofilament scaffolds. The core-shell fiber configuration significantly reduced production of pro-inflammatory cytokines to levels similar to those of gelatin monofilament scaffolds. In vitro, ES mechanical properties were significantly enhanced using CoA scaffolds; however, after grafting CoA- and gelatin-based ES to full-thickness excisional wounds on athymic mice, the in vitro mechanical advantage of CoA grafts was lost. A substantially increased inflammatory response to CoA-based ES was observed, with upregulation of IL-6 expression and a significant M2 macrophage presence. Additionally, expression of matrix metalloproteinase I was upregulated and collagen type I alpha 1 was downregulated in CoA ES two weeks after grafting. These results suggest that while coaxial scaffolds provide the ability to regulate biomechanics in vitro, further investigation of the inflammatory response to core materials is required to optimize this strategy for clinical use. STATEMENT OF SIGNIFICANCE: Engineered skin has been used to treat very large burn injuries. Despite its ability to heal these wounds, engineered skin exhibits reduced biomechanical properties making it challenging to manufacture and surgically apply. Coaxial fiber scaffolds have been utilized to tune the mechanical properties of engineered skin while maintaining optimal biological properties but it is not known how these perform on a patient especially with regards to their inflammatory response. The current study examines the biomechanical and inflammatory properties of coaxial scaffolds and uniaxial scaffolds in vitro and in vivo. The results show that the biological response to the scaffold materials is a critical determinant of tissue properties after grafting with reduced inflammation and rapid scaffold remodeling leading to stronger skin.
工程化皮肤（ES）在治疗烧伤创面方面比断层皮片移植物有许多优势。然而，ES 无论是在体外还是在移植后，通常都比正常的人类皮肤明显脆弱、弹性差、顺应性好。体外可以使用电纺同轴（CoA）支架来调整 ES 的生物力学性能。为了探索基于同轴支架的 ES 在体内应用的潜力，制备了两种具有生物活性明胶壳和可生物降解的聚乳酸（PLA）和聚己内酯（PCL）合成核的同轴支架，并与明胶单丝支架进行了比较。与明胶单丝支架相比，当在 PLA 和 PCL 单丝支架上培养时，成纤维细胞和巨噬细胞产生的炎症细胞因子白细胞介素 6（IL-6）和转化生长因子β-1 明显更高。核壳纤维结构显著降低了促炎细胞因子的产生，使其水平与明胶单丝支架相似。体外，使用 CoA 支架可显著增强 ES 的机械性能；然而，将 CoA 和基于明胶的 ES 移植到无胸腺小鼠的全层切除创面后，CoA 移植物的体外机械优势丧失。观察到对 CoA 基 ES 的炎症反应明显增加，IL-6 表达上调，M2 巨噬细胞明显存在。此外，移植后两周，CoA ES 中基质金属蛋白酶 I 的表达上调，I 型胶原蛋白α 1 的表达下调。这些结果表明，虽然同轴支架具有在体外调节生物力学的能力，但需要进一步研究核心材料的炎症反应，以优化这种策略用于临床应用。
工程化皮肤已用于治疗非常大的烧伤伤口。尽管它能够治愈这些伤口，但工程化皮肤表现出降低的生物力学性能，使其在制造和手术应用方面具有挑战性。同轴纤维支架已被用于调整工程化皮肤的机械性能，同时保持最佳的生物学特性，但尚不清楚这些在患者身上的表现如何，特别是在它们的炎症反应方面。本研究在体外和体内检查了同轴支架和单轴支架的生物力学和炎症特性。结果表明，支架材料的生物反应是移植后组织性能的关键决定因素，减少炎症和快速支架重塑导致更强的皮肤。
