Engineered ECM-Based Composite Tissue Flaps for Complex Defects Regeneration

The clinical demand for reconstructive tissue flaps is constantly rising. Those are crucial for bridging of substantial defects s, caused by severe pathologies, trauma and congenital anomalies. Proper integration of such flaps is crucial for optimal healing at the treatment site, especially when the defect is large and consist of both soft and hard tissue defects. Today, harvesting autologous flaps from patients is still the common treatment modality, with the downside of causing donor site morbidity. One key factor which is crucial for integration of large flaps is adequate vascularization of the tissue. Laboratory-made tissue engineered constructs, with their own rich vasculature and blood supply, may serve as an alternative for the current standard of care.

In the present work, support-cell populations were investigated for their potential as a source for the fabrication of highly vascularized tissue constructs. In vitro results showed rapid formation of mature vascular networks when endothelial cell (EC) were cultured with these cells. Transplantation of prevascularized constructs around a rat AV bundle model resulted in highly vascularized neo-tissues, with substantial host vessel invasion and remodeling of implanted grafts. High-resolution imaging enabled comprehensive analysis of whole vessel networks within the engineered tissues, showing differences between constructs fabricated from different cellular origins. Within engineered tissues, 3-dimensional vascular trees volume and graft penetration were assessed and quantified. Spatial orientation analysis of vasculature suggested a distinct orientation pattern of sprouting vessels when they were penetrating into the construct. Attempts to vascularize a hard tissue phase within engineered soft tissues were successful. These results emphasize the promising role of pre-vascularized engineered constructs for the creation of large reconstructive flaps. consisting of both soft and hard tissues.