College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China.
Lab Chip. 2016 Jul 5;16(14):2609-17. doi: 10.1039/c6lc00540c.
Microgels are favorable for numerous applications such as drug delivery, biomaterials science and tissue engineering. Conventionally, photolithographic methods and micro-molding techniques are extensively exploited to prepare microgels; however, they are, respectively, limited to photocrosslinkable polymers and inadequate to generate serially patterned hydrogels due to the static nature of utilized molds. Herein, we proposed a simple and versatile approach, termed pneumatic-aided micro-molding (PAM), to flexibly fabricate microgels with precise control over multiple cell types and microarchitectures of hydrogels through strategically designed pneumatic microvalves. Using the PAM approach, different cells were encapsulated in various hydrogels that had well-defined geometries. Additionally, single/multiple micro-channeled cell-laden microgels were fabricated, of which the shape, number and arrangement could be finely tuned by varying microvalve configurations. Moreover, multi-compartmental microgels comprising composite hydrogel structures were engineered following a two-step PAM, which demonstrated the utility for biomimetically constructing a three-dimensional (3D) liver microtissue composed of a radially orchestrated network of hepatic cords and sinusoids. The resulting microtissue resembled the organizational complexity of the liver lobule and was applied for the evaluation of acetaminophen-induced hepatotoxicity. Collectively, the PAM strategy could be a useful and powerful tool in biomedical engineering, in vitro 3D cell culture, and fundamental biological studies.
微凝胶在药物输送、生物材料科学和组织工程等众多领域都有广泛的应用。传统上，光光刻法和微成型技术被广泛用于制备微凝胶；然而，它们分别限于光交联聚合物，并且由于所使用的模具的静态性质，不足以生成连续图案化的水凝胶。在此，我们提出了一种简单而通用的方法，称为气动辅助微成型（PAM），通过策略性设计的气动微阀，可以灵活地制造具有精确控制的微凝胶，用于多种细胞类型和水凝胶的微结构。使用 PAM 方法，可以将不同的细胞封装在具有明确定义几何形状的各种水凝胶中。此外，可以制造单/多微通道细胞负载的微凝胶，其形状、数量和排列可以通过改变微阀的配置来精细调整。此外，通过两步 PAM 工程构建了包含复合水凝胶结构的多腔室微凝胶，这证明了用于仿生构建由肝索和窦状隙的径向协调网络组成的三维（3D）肝微组织的实用性。所得微组织类似于肝小叶的组织复杂性，并应用于评估对乙酰氨基酚诱导的肝毒性。总之，PAM 策略可以成为生物医学工程、体外 3D 细胞培养和基础生物学研究中的有用和强大工具。
