In bottom-up tissue engineering, small modular units of cells and biomaterials are assembled toward ​larger and more complex ones. In conjunction with a new implementation of this approach, a novel method to fabricate microscale objects from biopolymers by thermal imprinting on water-soluble sacrificial layers is presented. By this means, geometrically well-defined objects could be obtained without involving toxic agents in the form of photoinitiators. The micro-objects were used as cell-adhesive substrates and cell spacers in engineered tissues created by cell-guided assembly of the objects. Such constructs can be applied both for in vitro studies and clinical treatments. Clinically relevantly sized aggregates comprised of cells and micro-objects retained their viability up to 2 weeks of culture. The aggregation behavior of cells and objects showed to depend on the type and number of cells applied. To demonstrate the micro-objects’ potential for engineering vascularized tissues, small aggregates of human bone marrow stromal cells (hMSCs) and micro-objects were coated with a layer of human umbilical vein endothelial cells (HUVECs) and fused into larger tissue constructs, resulting in HUVEC-rich regions at the aggregates' interfaces. This three-dimensional network-type spatial cellular organization could foster the establishment of (premature) vascular structures as a vital prerequisite of, for example, bottom-up-engineered bone-like tissue.

在自下而上的组织工程中，细胞和生物材料的小型模块化单元被组装成更大，更复杂的单元。结合这种方法的新实现方式，提出了一种通过在水溶性牺牲层上热压印从生物聚合物中制备微尺度物体的新颖方法。通过这种方法，可以获得几何形状明确的物体，而无需涉及光引发剂形式的有毒物质。微型物体被用作细胞粘附的基质和细胞隔离物，这些细胞和间隔物是通过物体的细胞引导组装而产生的工程组织中的。这样的构建体可用于体外研究和临床治疗。由细胞和微小物体组成的具有临床相关大小的聚集体可在长达2周的培养中保持其活力。细胞和物体的聚集行为表明取决于所施加细胞的类型和数量。为了证明微对象对血管化组织进行工程改造的潜力，将人骨髓基质细胞（hMSCs）和微对象的小聚集体涂上一层人脐静脉内皮细胞（HUVEC），并融合成较大的组织结构，在聚集体界面处富含HUVEC的区域中。这种三维网络类型的空间细胞组织可以促进（过早的）血管结构的建立，这是例如自下而上工程化的骨样组织的重要先决条件。