Regenerative Facial Reconstruction of Terminal Stage Osteoradionecrosis and Other Advanced Craniofacial Diseases with Adult Cultured Stem and Progenitor Cells

Abstract

Treatment options in cases of severe craniofacial disorders with bone loss and tissue damage are usually limited to vascularized and nonvascularized tissue transfers, allografts, mechanical devices and, more recently, facial transplantation. Despite the therapies available, the demand for new approaches is realized in cases where current therapies are unable to resume form and function. This study presents the feasibility of alternative treatments based on cultured bone marrow cells that yield mixed populations of mesenchymal, hematopoietic, and endothelial lineages at very early stages implemented as part of a novel regenerative procedure. One hundred milliliters of a bone marrow aspirate was inoculated into the automated single-pass perfusion technology system, AastromReplicell, for the development of the cellular product, tissue repair cells. After 12 days of incubation, cells were exposed to a specially designed osteogenic environment in an autogenous fibrin-rich and platelet-rich clot and membrane with a mineral base of β-tricalcium phosphate and hydroxyapatite. A case of maxillary and mandibular radionecrosis (stage IIIR) with pathologic fracture presented early osteogenesis, total recovery from alveolar nerve anesthesia, facial nerve reinnervation, and skin regeneration. Another case with nonhealed fracture, bone loss, and bilateral paresthesia demonstrated callus formation, bone regeneration, and nerve recovery. Finally, maxillary bone regenerated after massive deficiency. Oral functional restoration with implants and fixed prosthesis was accomplished in all cases. After nerve, bone, skin, and vessel formation in three patients with severe abnormality, bone marrow-derived mixed cultured stem cell lineages could be considered a new paradigmatic approach to advanced disease.