Prefabrication of vascularized large bone grafts

Abstract

Infection, trauma or neoplasia can lead to extensive bone tissue loss. Current reconstructive approaches for large, complex bone defects, especially in the maxillo-facial region, rely on autologous bone grafting. However, reconstruction by autologous tissue transfer can encounter major difficulties. Not only is tissue transfer restricted by donor site morbidity and limited availability, the three-dimensional suitability of donor and recipient tissue can represent a major hurdle. To avoid these shortcomings, it would be of high interest to generate a prefabricated, vascularized, custom-shapeable bone graft. The envisioned bone graft surrogate relies on the concept of combining an efficient vascularization strategy with an engineered material, providing robust bone formation. In this thesis I investigate whether an arteriovenous (AV) bundle is suitable as an efficient vascularization method, able to fully revitalize a critically sized bone graft. In combination with an osteoconductive ceramic material and a living cell source, the stromal vascular fraction (SVF) from adipose tissue, the AV bundle is able to induce and support bone formation. A newly developed, contrast-enhanced, microtomographic imaging technique made it possible to critically assess vascularization and bone formation within such a graft in its entirety. Eventually, implementation of an engineered matrix, useable as an off-the-shelf material, in the above mentioned graft allowed to generate a germ of osteoinduction and vascularization. The developed concept of a prefabricated, pedicled, large bone graft, customizable to the patients’ needs, offers a vast variety of clinical applications.