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Tissue-engineered autologous grafts for facial bone reconstruction

Anatomically shaped living bone formed in a portable bioreactor using autologous cells and bone matrix repaired the facial ramus-condyle unit in pigs. Saving face Restoring your reputation after a social gaffe may be challenging, but perhaps welcomed in comparison to saving face through restoration of actual bone structure. A delicate and precise process, facial bone reconstruction currently uses bone grafts from the same patient. Cell- and biomaterial-based approaches could benefit this field by providing personalized grafts for deformities of all shapes and sizes. Bhumiratana and colleagues therefore designed a maxillofacial reconstructive strategy centered on a combination of stem cells, decellularized bone, and a custom-designed perfusion bioreactor. The bone was first shaped to the defect in the ramus-condyle unit of minipigs, which have similar jaw anatomies and weight-bearing properties as humans. Then, stem cells were cultured on the bone for several weeks. To mimic the manufacturing and transport chain that could be involved in reconstructing human facial bones, then authors shipped the bioreactor with the living bone inside the site of surgery. Paired histological and image analysis showed that the implanted scaffold material integrated with host tissue, formed new bone, and was vascularized extensively, but only if cells were present. Growing such anatomically correct, large-scale bone constructs could vastly improve regenerative medicine options for patients with craniofacial bone deformities. Facial deformities require precise reconstruction of the appearance and function of the original tissue. The current standard of care—the use of bone harvested from another region in the body—has major limitations, including pain and comorbidities associated with surgery. We have engineered one of the most geometrically complex facial bones by using autologous stromal/stem cells, native bovine bone matrix, and a perfusion bioreactor for the growth and transport of living grafts, without bone morphogenetic proteins. The ramus-condyle unit, the most eminent load-bearing bone in the skull, was reconstructed using an image-guided personalized approach in skeletally mature Yucatán minipigs (human-scale preclinical model). We used clinically approved decellularized bovine trabecular bone as a scaffolding material and crafted it into an anatomically correct shape using image-guided micromilling to fit the defect. Autologous adipose-derived stromal/stem cells were seeded into the scaffold and cultured in perfusion for 3 weeks in a specialized bioreactor to form immature bone tissue. Six months after implantation, the engineered grafts maintained their anatomical structure, integrated with native tissues, and generated greater volume of new bone and greater vascular infiltration than either nonseeded anatomical scaffolds or untreated defects. This translational study demonstrates feasibility of facial bone reconstruction using autologous, anatomically shaped, living grafts formed in vitro, and presents a platform for personalized bone tissue engineering.