Tissues derived from human pluripotent stem cells (hPSCs) often represent early stages of fetal development, but mature at the molecular and structural level when transplanted into immunocompromised mice. hPSC-derived lung organoids (HLOs) transplantation has been further enhanced with biomaterial scaffolds, where HLOs had improved tissue structure and cellular differentiation. Here, our goal was to define the physico-chemical biomaterial properties that maximally enhanced transplant efficiency, including features such as the polymer type, degradation, and pore interconnectivity of the scaffolds. We found that transplantation of HLOs on microporous scaffolds formed from poly (ethylene glycol) (PEG) hydrogel scaffolds inhibit growth and maturation, and the transplanted HLOs possessed mostly immature lung progenitors. On the other hand, HLOs transplanted on poly (lactide-co-glycolide) (PLG) scaffolds or polycaprolactone (PCL) led to tube-like structures that resembled both the structure and cellular diversity of an adult airway. Our data suggests that scaffold pore interconnectivity and polymer degradation contributed to the maturation, and we found that the size of the airway structures and the total size of the transplanted tissue was influenced by the material degradation rate. Collectively, these biomaterial platforms provide a set of tools to promote maturation of the tissues and to control the size and structure of the organoids.

中文翻译：

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人肺类器官在物理化学生物材料特性的指导下发育成成人气道样结构。

源自人类多能干细胞（hPSC）的组织通常代表胎儿发育的早期阶段，但当移植到免疫功能低下的小鼠体内时，其在分子和结构水平上已成熟。生物材料支架进一步增强了 hPSC 衍生的肺类器官 (HLO) 移植，其中 HLO 改善了组织结构和细胞分化。在这里，我们的目标是定义最大限度地提高移植效率的物理化学生物材料特性，包括支架的聚合物类型、降解和孔互连性等特征。我们发现，将 HLO 移植到由聚乙二醇（PEG）水凝胶支架形成的微孔支架上会抑制生长和成熟，并且移植的 HLO 大部分具有未成熟的肺祖细胞。另一方面，移植到聚丙交酯乙交酯 (PLG) 支架或聚己内酯 (PCL) 上的 HLO 产生类似于成人气道的结构和细胞多样性的管状结构。我们的数据表明支架孔隙互连性和聚合物降解有助于成熟，并且我们发现气道结构的尺寸和移植组织的总尺寸受到材料降解率的影响。总的来说，这些生物材料平台提供了一套促进组织成熟并控制类器官的大小和结构的工具。