DeBari Megan K, Ng Wai Hoe, Griffin Mallory D, Kokai Lauren E, Marra Kacey G, Rubin J Peter, Ren Xi, Abbott Rosalyn D
Department of Materials Science & Engineering, Carnegie Mellon University, Pittsburgh, PA 15203, USA.
Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15203, USA.
Biomimetics (Basel). 2021 Sep 18;6(3):52. doi: 10.3390/biomimetics6030052.
Critically sized defects in subcutaneous white adipose tissue result in extensive disfigurement and dysfunction and remain a reconstructive challenge for surgeons; as larger defect sizes are correlated with higher rates of complications and failure due to insufficient vascularization following implantation. Our study demonstrates, for the first time, a method to engineer perfusable, pre-vascularized, high-density adipose grafts that combine patient-derived adipose cells with a decellularized lung matrix (DLM). The lung is one of the most vascularized organs with high flow, low resistance, and a large blood-alveolar interface separated by a thin basement membrane. For our work, the large volume capacity within the alveolar compartment was repurposed for high-density adipose cell filling, while the acellular vascular bed provided efficient graft perfusion throughout. Both adipocytes and hASCs were successfully delivered and remained in the alveolar space even after weeks of culture. While adipose-derived cells maintained their morphology and functionality in both static and perfusion DLM cultures, perfusion culture offered enhanced outcomes over static culture. Furthermore, we demonstrate that endothelial cells seamlessly integrate into the acellular vascular tree of the DLM with adipocytes. These results support that the DLM is a unique platform for creating vascularized adipose tissue grafts for large defect filling.
皮下白色脂肪组织中的临界尺寸缺损会导致广泛的毁容和功能障碍，仍然是外科医生面临的重建挑战；因为较大的缺损尺寸与植入后血管化不足导致的较高并发症发生率和失败率相关。我们的研究首次展示了一种构建可灌注、预血管化、高密度脂肪移植物的方法，该方法将患者来源的脂肪细胞与去细胞肺基质（DLM）相结合。肺是血管化程度最高的器官之一，血流高、阻力低，且有一个由薄基底膜分隔的大血-肺泡界面。在我们的研究中，肺泡腔的大容量被重新用于高密度脂肪细胞填充，而去细胞血管床则为整个移植物提供了有效的灌注。脂肪细胞和人脂肪干细胞都成功递送并保留在肺泡空间内，即使经过数周培养也是如此。虽然脂肪来源的细胞在静态和灌注DLM培养中都保持了它们的形态和功能，但灌注培养比静态培养的效果更好。此外，我们证明内皮细胞能与脂肪细胞无缝整合到DLM的去细胞血管树中。这些结果支持DLM是一个用于创建血管化脂肪组织移植物以填充大缺损的独特平台。
