Department of Bioengineering, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA.
Department of Pediatrics, Children's Hospital Colorado, Aurora, CO, USA.
J Biomed Mater Res A. 2021 Nov;109(11):2154-2163. doi: 10.1002/jbm.a.37201. Epub 2021 Apr 20.
Congenital heart defects (CHDs) are the leading cause of death in live-born infants. Currently, patches used in the repair of CHDs are exclusively inert and non-degradable, which increases the risk of arrhythmia, follow-up surgeries, and sudden cardiac death. In this preliminary study, we sought to fabricate biodegradable scaffolds that can support cardiac regeneration in the repair of CHDs. We electrospun biodegradable scaffolds using various blends of polyurethane (PU) and polycaprolactone (PCL) with and without sacrificial poly(ethylene oxide) (PEO) particles and assessed the mechanical properties, cell infiltration levels, and inflammatory response in vitro (surface cell seeding) and in vivo (subcutaneous mouse implant). We hypothesized that a blend of the two polymers would preserve the low stiffness of PU as well as the high cell infiltration observed in PCL scaffolds. The inclusion of PU in the blends, even as low as 10%, decreased cell infiltration both in vitro and in vivo. The inclusion of sacrificial PEO increased pore sizes, reduced Young's moduli, and reduced the inflammatory response in all scaffold types. Collectively, we have concluded that a PCL patch electrospun with sacrificial PEO particles is the most promising scaffold for further assessment as in our heart defect model.
先天性心脏缺陷（CHD）是活产婴儿死亡的主要原因。目前，用于 CHD 修复的补丁完全是惰性和不可降解的，这增加了心律失常、后续手术和心脏性猝死的风险。在这项初步研究中，我们试图制造可生物降解的支架，以支持心脏再生，用于 CHD 的修复。我们使用不同比例的聚氨酯（PU）和聚己内酯（PCL）以及带有和不带有牺牲性聚（氧化乙烯）（PEO）颗粒的混合物来静电纺丝生物可降解支架，并评估了体外（表面细胞接种）和体内（皮下小鼠植入）的机械性能、细胞浸润水平和炎症反应。我们假设两种聚合物的混合物将保留 PU 的低刚度以及在 PCL 支架中观察到的高细胞浸润。PU 的掺入，即使低至 10%，也会降低体外和体内的细胞浸润。所有支架类型中牺牲性 PEO 的加入都会增加孔径、降低杨氏模量并减少炎症反应。总的来说，我们得出的结论是，带有牺牲性 PEO 颗粒的 PCL 贴片电纺丝是最有前途的支架，可进一步评估我们的心脏缺陷模型。
