Anatomically-Shaped Autogenous Engineered Bone Graft for TMJ Condyle Reconstruction: Mid-point analysis
Statement of the problem
Maxillofacial surgeons must reconstruct complex deformities that require functional and esthetic precision. Ideal grafts must be predictable and exactly match 3D form unique to every patient's defect in order to restore function. Current standards of practice require lengthy procedures, secondary surgical sites, immense resources, but still yield compromised results. With the advancements in tissue engineering through regulation of osteogenic differentiation and functional assembly of stem cells, we are able to produce autogenous bone grafts engineered in vitro. Here we report our experience with custom-made bone grafts of the TMJ condyle and ramus with the use of autogenous adipose stem cells (ASCs) in a large-animal study.
Materials and methods
Yucatan minipigs were randomly divided into 3 groups: (i) condylectomy (n=2), (ii) scaffold implantation (n=6), and (iii) autogenous engineered bone graft implantation (n=6). The process for engineering anatomically-shaped TMJ condyle for implantation was adapted from previous work.1 In brief, facial skeletons of each pig were CT scanned and reconstructed in 3D. Condyle/ramus units were chosen for reconstruction (Fig. 1A). Anatomically-shaped scaffolds for each pig were fabricated from trabecular bone of adult bovine knees based on previously reported methods.1 To engineer the bone grafts, scaffolds were seeded with autogenous ASCs isolated from subcutaneous fat of each pig.2 The grafts were cultured in osteogenic medium in specially designed perfusion bioreactors [Fig. 1B] for 3 weeks prior to implantation to facilitate stem cell growth, osteogenic differentiation, and bone matrix deposition. Condylectomies to include a portion of the ramus were planned virtually and carried out under general anesthesia. The pigs were reconstructed with a scaffold alone or autogenous engineered bone graft. All grafts were rigidly fixated using 2.0mm titanium miniplates. The planned duration of study is 6 months. We report here the mid-point analysis in which 2 pigs from each implantation group were sacrificed 3 months post-implantation. CT scans were conducted after surgery, at 6 weeks, and 3 months. TMJ condyles were harvested after sacrifice and assessed for graft remodeling in terms of compactness, integration, and resorption.
Results
Bone grafts were successfully fabricated with the exact shape and size unique to each condyle [Fig. 1C]. Cell seeding of scaffolds and cultivation resulted in fully cellularized engineered bone tissue. All pigs survived the surgery without complications. At 3 months, pigs with untreated condylectomies regenerated incomplete ramus-condyle units (RCU). Pigs with scaffold implantation showed incomplete regeneration with significant scaffold resorption [Fig. 1D]. In contrast, pigs with autogenous engineered bone displayed regeneration as well as integration of the RCU [Fig. 1E]. The harvested condyles at 3 months demonstrated clear differences between the groups, with regeneration of a rigid and functional mandible in the autogenous engineered bone graft group. The scaffold-only group failed to obtain comparable results, and healed with graft resorption and fibrous ingrowth.
Conclusions
Based on the mid-point results of the large animal model, autogenous engineered bone grafts maintain tissue volume and enhance regeneration, yielding a promising treatment for facial bone reconstruction.
Figure 1. Mid-point results of tissue engineered reconstruction of TMJ in Yucatan minipig. (A) 3D reconstructed pig mandible with selected TMJ condyle for reconstruction; (B) Perfusion bioreactor for cultivation of autogenous bone graft; (C) Engineered graft and extracted condyle; 3-month post-implantation CT image of pigs receiving (D) scaffold implantation and (E) autogenous tissue engineered bone implantation.
References
1. Grayson WL et.al., Engineering anatomically shaped human bone grafts, Proc. Natl. Acad. Sci.; 2010, 107(8):3299-304
2. Williams KJ et.al., Isolation and characterization of porcine adipose tissue-derived adult stem cells, Cells Tissues Organs, 2008; 188:251-258
Acknowledgements
The work was supported by BioAcellerate funding of the New York City Partnership Foundation (grant CU11-1915 to GVN).