Abstract：
Neonates with congenital diaphragmatic hernia often require surgical defect closure with a patch. Alternatives to native diaphragmatic tissue are critically needed for this paediatric surgery. The clinical efficacy of mesh patches is limited by complications associated with residual foreign material and by hernia recurrence. In this study, we used a novel bio-3D printer method to generate large scaffold-free tissue patches composed of human cells. The resulting large tissue constructs had high elasticity and strength. Cellular patches were transplanted into rats with surgically created diaphragmatic defects. Rats survived for over 710 days after implantation of tissue constructs. CT confirmed complete tissue integration of the grafts during rat growth. Histology revealed regeneration of muscle structure, neovascularization, and neuronal networks within the reconstructed diaphragms. Our results demonstrate that created cellular patches are a highly safe and effective therapeutic strategy for repairing diaphragmatic defects, and thus pave the way for a clinical trial.
摘要：
患有先天性膈疝的新生儿通常需要用补片闭合手术缺损。这种儿科手术迫切需要天然膈组织的替代品。网状补片的临床疗效受到与残留异物相关的并发症和疝复发的限制。在这项研究中,我们使用一种新颖的生物3D打印机方法来生成由人体细胞组成的大型无支架组织贴片。所得的大组织构建体具有高弹性和强度。将细胞斑块移植到具有手术产生的diaphragm肌缺损的大鼠中。大鼠在植入组织构建体后存活超过710天。CT证实了大鼠生长过程中移植物的完全组织整合。组织学显示肌肉结构再生，新生血管形成,和重建的隔膜内的神经元网络。我们的结果表明，创建的细胞补丁是修复膈肌缺损的高度安全和有效的治疗策略，从而为临床试验铺平道路。
