Significance Effective restoration of large soft tissue defects requires the use of tissue flaps, with viability that is largely determined by degree of vascularization. In view of the tedious transfer procedures and donor site morbidity associated with autologous flaps, this work set out to design and evaluate an engineered muscle flap featuring a robust vascular port formed from preseeded endothelial cells and host vasculature. The implanted flap was highly vascularized, well-perfused, and anastomosed with host vessels. Engineered flaps of this nature promise to circumvent the need to harvest and transfer massive tissue volumes, while avoiding the consequential complications.

Mechanical forces play an important role in the initial stages of embryo development; yet, the influence of forces, particularly of tensile forces, on embryonic stem cell differentiation is still unknown. The effects of tensile forces on mouse embryonic stem cell (mESC) differentiation within a three-dimensional (3D) environment were examined using an advanced bioreactor system. Uniaxial static or dynamic stretch was applied on cell-embedded collagen constructs. Six-day-long cyclic stretching of the seeded constructs led to a fourfold increase in Brachyury (BRACH-T) expression, associated with the primitive streak phase in gastrulation, confirmed also by immunofluorescence staining. Further examination of gene expression characteristic of mESC differentiation and pluripotency, under the same conditions, revealed changes mostly related to mesodermal processes. Additionally, downregulation of genes related to pluripotency and stemness was observed. Cyclic stretching of the 3D constructs resulted in actin fiber alignment parallel to the stretching direction. BRACH-T expression decreased under cyclic stretching with addition of myosin II inhibitor. No significant changes in gene expression were observed when mESCs were first differentiated in the form of embryoid bodies and then exposed to cyclic stretching, suggesting that forces primarily influence nondifferentiated cells. Understanding the effects of forces on stem cell differentiation provides a means of controlling their differentiation for later use in regenerative medicine applications and sheds light on their involvement in embryogenesis.

The central role of prevascularization of engineered tissue grafts in postimplantational survival and integration is becoming increasingly appreciated. An in‐depth understanding of the regulating factors and intricacies of generation of three‐dimensional vascular networks in vitro will facilitate effective fabrication of clinically relevant vascularized tissues. In this review we aim to examine the influence of different biomaterials on vasculogenesis and angiogenesis, with particular focus on the impact of various matrix properties, such as composition, stiffness and geometry, on the resulting vasculature. Additionally, the contribution of externally applied mechanical forces, mimicking blood flow patterns, to tissue vascularization efforts is reviewed. We present here pivotal studies focusing on the influence of mechanical forces, such as shear stress and stretching tension, on vascular network formation in biomaterial‐based scaffolds. Comprehensive understanding of the key factors dictating the patterns and functionality of engineered vasculature will facilitate more efficient fabrication of viable tissue grafts, with a broad range of medical applications.