3D-Inspired Bioengineered Tissue Flaps for Tissue Regeneration

Objectives: Functional regeneration of complex large-scaled defects requires heavily vascularized tissue grafts with patient-specific anatomy. Autologous tissue harvest, considered the standard of care in surgical settings, has considerable drawbacks such as tissue-site morbidity and post-operative pain. Tissue engineering approaches relying on bio-inspired additive manufacturing techniques and induction of vascular connectivity with hosts can promote graft sustainability while enabling proper adaptation within tissue defects during engraftment.
Methods: Neo-tissue flaps developed via stem-cells loading onto biocompatible and biodegradable soft tissue scaffolds. Following in-vitro induction, bioengineered scaffolds are combined with a bone matrix to yield a composite neo-tissue. These, in turn, undergo axial vascularization in a rat arteriovenous model. Both ex vivo and in-vivo assessments of maturation and implantation are performed.
Results: Pre-vascularization and osteogenic induction of tissue constructs are validated in vitro and in vivo, and high-resolution micro-computed tomography is employed to assess bone deposition, remodeling, and micro-vessels within neo-tissues.
Conclusions: The presented methodology promotes neo-tissue creation for soft and hard tissue bridging. In addition, the underlying angiogenic connectivity between host and graft is evaluated, and upscaling of human-sized constructs is performed.