Guided Self-Generation of Vascularized Neo-Bone for Autologous Reconstruction of Large Mandibular Defects.

Reconstruction of large mandibular defects is complex and challenging. The authors aimed to individually self-generate a large vascularized bone construct for autologous transplantation without the use of exogenous additives based on the concept of guided self-generation. Using computer-aided design and manufacturing a large size goat mandibular bone was reconstructed in 3 dimensions. Its negative mold printed from hydroxylapatite was temporarily embedded into the costal periosteum along with a contralateral demineralized bone matrix scaffold as control. After 3 months, a mandibular bone construct was obtained and used for autologous transplantation. Osteogenesis and angiogenesis were assessed by real-time imaging, histology, and biomechanical tests during neo-bone formation and up to 6 months after transplantation surgery. A total of 20 animals received implantation of a mandibular bone negative mold along with a contralateral demineralized bone matrix scaffold. Resulting negative mold mandibular bone constructs showed anatomically, histologically, and functionally similar characteristics compared with native controls. Only 1 goat presented partial fibrosis during construct generation with subsequent absorbtion after reconstruction. The absence of exogenous cells, growth factors, and scaffolds facilitated direct translation of this novel concept into clinical application. Further studies are needed to determine functional long-term outcomes and possible extensions to other tissues and organs.