Our previous work has discovered that biological root structures regenerated in rats upon extraction of the native mandibular incisor and replacement with an anatomically correct scaffold. However, SDF1 used in our previous work recruited excessive numbers of cells, some of which are anticipated to be inflammatory cells. Here, we attempt to scale up tooth root regeneration in a large animal model and regenerate tooth roots with amelogenin, a protein that is known to induce mineralization.
Method:
We first fabricated the anatomically correct biological scaffolds using a composite of poly-e-caprolactone (PCL) and hydroxyapatite (HA) by 3D bioprinting. Upon extraction of the entire mandibular incisors in minipigs (N=16), bioscaffolds infused with ameloginin (AMG @10 ng/mL) (N=8) and/or bone morphogenetic protein-7 (BMP7 @10 ng/mL) (N=8) were implanted into extraction sockets. PBS-infused scaffolds served as controls (N=3).
Result:
Following 6-month in vivo implantation, radiological and µCT assessments were used to evaluate the outcome of root formation. Mineralized tissue was formed in either BMP7-infused and AMGN-infused bioscaffolds. However, BMP7-infused bioscaffolds formed significantly more mineralized tissues than the AMG-infused bioscaffolds. Given that PCL-HA undergoes biocompatible degradation over time, it is probable that additional mineralized tissue may continue to form until complete biomaterial degradation.
Conclusion:
These findings indicated that AMG- or BMP7 is capable of inducing mineralization upon cells that have migrated into microchannels of PCL-HA scaffolds. We are in the process of analyzing the quality of mineralized tooth roots and endogenous cell sources that are responsible for mineralized tissue regeneration.