Purpose: The authors propose a novel method for primary alveolar cleft bony reconstruction that avoids donor site morbidity and does not require close approximation of alveolar segments as necessitated by gingivoperiosteoplasty. The study aims to provide radiographic evidence of de novo synthesis of bone using recombinant human bone morphogenic protein-2 (rhBMP-2).
Methods: This IRB-approved class IV study retrospectively evaluated primary alveolar cleft patients from 2004-2006. Subjects chose an off-label application of rhBMP-2 impregnated on an absorbable collagen sponge (ACS) carrier to reconstruct alveolar clefts, all greater than 3 mm in width. The surgical technique used for soft tissue closure, developmental field reassignment (DFR) is not a gingivoperiosteoplasty, and is applicable to alveolar clefts of virtually any size. DFR produces a periosteal “pocket” containing mesenchymal stem cells (MSCs) sensitive to cytokines, such as BMP-2. Inductive conversion of MSCs to osteoblasts by BMP-2 is known as in-situ osteogenesis (ISO). 17 cleft sites treated with ISO were evaluated at 6 months post-operatively using low-dose spiral CT with 1 mm cuts limited to the maxilla. Alveolar bone density (Hounsfield Units-HU) was assessed by three radiologists. Both the 1mm thin-cut CT scans and the same area for ROI, 11 mm², were employed to minimize disparities in volume averaging of the HU calculation. Dental arch fusion was defined as continuous filling of the previous air- or mesenchymal-filled alveolar cleft with radiographic HU density in the ROI greater than 226, table 1.
Results: In 16 of 17 cleft sites ISO produced trabecular bone that filled the implantation site both transversely and vertically. The baseline alveolar cleft mean tissue density as measured by the three radiologists preoperatively increased from (-38 HU, -83 HU, -129 HU to +650 HU, +573 HU, +693 HU) at 6-months postoperatively, figure 1. Interestingly, the cleft that did not show trabecular bone formation demonstrated a significant HU increase. Failure in this particular case was attributed to excessive irrigation of the implant site prior to final closure leading to a “dilution effect” of protein from the sponge.
Conclusion: Stem cell stimulation using rhBMP-2/ACS offers highly effective radiographic and clinical evidence for unification of the dental arch without donor site morbidity. Long-term follow-up studies for this initial cohort are underway to examine information on orthodontic relationships and cephalometrics using cone-beam CT technology.