Construction of vascularized tissue-engineered breast with dual angiogenic and adipogenic micro-tissues

Hydrogel-based micro-tissue engineering technique, a bottom-up approach, is promising in constructing soft tissue of large size with homogeneous spatial distribution and superior regeneration capacity compared to the top-down approach. However, most of the studies employed micro-tissues with simple mesenchymal stem cells, which could hardly meet the growth of matrix and vessels. Therefore, we recommend a dual micro-tissues assembly strategy to construct vascularized tissue-engineered breast grafts (TEBGs). Adipose micro-tissues (AMs) and vessel micro-tissues (VMs) were fabricated by seeding adipose-derived stem cells (ADSCs) and human umbilical vein endothelial cells (HUVECs) on collagen microgels (COLs) with a uniform diameter of ∼250 ​μm, respectively. TEBGs were constructed by injecting the dual micro-tissues into 3D printed breast-like Thermoplastic Urethane (TPU) scaffolds, then implanted into the subcutaneous pockets on the back of nude mice. After 3 months of implantation, TEBGs based on dual micro-tissues performed larger volume of adipose tissue regeneration and neo-vessel formation compared to TEBGs based on single AMs. This study extends the application of micro-tissue engineering technique for the construction of soft grafts, and is expected to be useful for creating heterogeneous tissue constructs in the future.