Vascularization in Biofabrication: Innovative Strategies for Advanced Tissue Models

The increasing demand for tissue and organ replacement has positioned biofabrication as a transformative field within regenerative medicine. Biofabrication is an interdisciplinary approach that combines cells, biomaterials, and bioactive molecules to generate biologically functioning structures and tissue models. However, the size of biofabricated constructs often remains limited due to the lack of vascular structures. Cells located in the inner regions of larger constructs suffer from a lack of oxygen and nutrients, which results in hypoxia and reduced cell viability. Furthermore, integration into the host vasculature is crucial for the long-term survival of constructs intended for in vivo implantation. Consequently, strategies to improve the vascularization of biofabricated constructs have gained significant attention. In this review, we focus on approaches for the in vitro and in vivo vascularization of biofabricated constructs. We summarize the types and sources of vascular cells used in biofabrication, as well as the signaling molecules and biomaterials that can be incorporated into biofabricated scaffolds. A special focus is placed on advanced vascularization strategies such as the in ovo chorioallantoic membrane (CAM) and in vivo arteriovenous (AV) loop models. Furthermore, we describe the role of vascularization in advanced tissue models used for disease modeling and drug screening. Although the clinical translation of biofabricated constructs is still limited by a lack of vasculature and size constraints, biofabrication offers great potential for tissue replacement, personalized medicine, and the reduction of animal experiments.