Abstract：
Despite the crucial role of lymphangiogenesis during development and in several diseases with implications for tissue regeneration, immunity, and cancer, there are significantly fewer tools to understand this process relative to angiogenesis. While there has been a major surge in modeling angiogenesis with microphysiological systems, they have not been rigorously optimized or standardized to enable the recreation of the dynamics of lymphangiogenesis. Here, a Lymphangiogenesis-Chip (L-Chip) is engineered, within which new sprouts form and mature depending upon the imposition of interstitial flow, growth factor gradients, and pre-conditioning of endothelial cells with growth factors. The L-Chip reveals the independent and combinatorial effects of these mechanical and biochemical determinants of lymphangiogenesis, thus ultimately resulting in sprouts emerging from a parent vessel and maturing into tubular structures up to 1 mm in length within 4 days, exceeding prior art. Further, when the constitution of the pre-conditioning cocktail and the growth factor cocktail used to initiate and promote lymphangiogenesis are dissected, it is found that endocan (ESM-1) results in more dominant lymphangiogenesis relative to angiogenesis. Therefore, The L-Chip provides a foundation for standardizing the microfluidics assays specific to lymphangiogenesis and for accelerating its basic and translational science at par with angiogenesis.
摘要：
尽管淋巴管生成在发育过程中和对组织再生有影响的几种疾病中起着至关重要的作用，豁免权,和癌症，相对于血管生成，了解这一过程的工具明显较少。虽然在用微生理系统模拟血管生成方面有很大的进展，它们尚未经过严格的优化或标准化，以重新创建淋巴管生成的动力学。这里,设计了淋巴管生成芯片（L-Chip），在其中，新的芽形成和成熟取决于间质流的强加，生长因子梯度，和用生长因子预处理内皮细胞。L-Chip揭示了淋巴管生成的这些机械和生化决定因素的独立和组合作用，因此最终导致芽从亲本血管中出现，并在4天内成熟成长度达1毫米的管状结构，超过现有技术。Further,当预处理鸡尾酒和用于启动和促进淋巴管生成的生长因子鸡尾酒的组成被解剖时，已发现,相对于血管生成,内皮蛋白聚糖(ESM-1)导致更显性的淋巴管生成。因此,L-Chip为标准化针对淋巴管生成的微流体测定以及加速其与血管生成同等的基础和转化科学提供了基础。
