Vascularized ECM based Composite Grafts for Complex Reconstructions

Complex tissue defects such as those inflicted by severe trauma or oncogenic ablation, require complicated approaches for adequate reconstruction. While vascularized soft and hard tissue grafts harvested from patients (autografts) are still considered as the gold standard for treatment, limited quantity and donor site morbidity remains as major hurdles in clinical settings. Numerous bone scaffolds combined with harvested flaps have been investigated as models for bone vascularization and osteogenesis. However, engineering composite scaffolds consisting of both soft and hard tissue phases is still a challenging goal. In addition, since delivery of oxygen and nutrients to engrafted bone constructs poses a major hurdle in bone-defect healing, adequate construct vascularization remains a limiting factor.

We have recently engineered vascularized tissue constructs both in-vitro and in-vivo. Following in vivo implantation of pre vascularized constructs, scaffolds undergo extensive vascular development and remodeling. Using high-resolution micro-CT scanning, neo-tissues vasculature was imaged and analyzed up to 10um in diameter. When these engineered constructs were combined with decellularized bone scaffolds, perfusion and extensive vascular penetration were also verified. These composite neo-tissues were assessed for their ability to support the regeneration of a complex tissue defect in vivo, which includes a combined soft and hard tissue injury.