The main advantage of growth factor-aided tissue engineering is the avoidance of a second surgical site needed for the harvest of autologous bone. This results in shortening of the operation time, absence of donor site morbidity, shorter hospital stay and reduction of overall cost.
Promising results with growth factor-aided tissue engineering techniques have been obtained in several fields. However, for the reconstruction of the alveolar cleft in CLAP, only three studies were found that assessed growth factor-aided bone tissue engineering techniques and met our selection criteria. We found no studies on BMP-7, TGF-β, PDGF, IGF, FGF, VEGF or PRP that met our selection criteria. The three studies that met our selection criteria all assessed BMP-2-aided bone tissue engineering. These three studies used the same bone tissue engineering kit (Infuse® Bone Graft) for the reconstruction of clefts in the experimental group and autologous cancellous bone of the iliac crest in the control group. It is remarkable that only studies with BMP-2 were published and that these studies all used the same product produced by the same company. The similarities with regard to study design and the growth factor used make comparison of the studies feasible. On the other hand, the patient numbers in the three studies are small, and there was some variation in the timing of the procedure: in two studies, the alveolar clefts were reconstructed during the stage of mixed dentition [25
], whereas in the other study, clefts were reconstructed in skeletally mature patients [26
]. The volume of the alveolar cleft prior to surgery also varied between the three studies, namely Herford et al. [27
] reported a much greater volume of the preoperative cleft. This may be explained by the use of preoperative orthodontic expansion of the maxillary segments by Alonso et al. [25
] and Dickinson et al. [26
]. As to the difference in volume of the cleft between Alonso et al. [25
] and Dickinson et al. [26
], the different timing of the procedure should again be taken into account. Nevertheless, the results clearly indicate that rhBMP-2 delivered in an absorbable collagen sponge carrier can create a bony bridge in alveolar cleft patients with sufficient volumes of bone, comparable with the amount achieved in iliac crest cancellous bone grafting. An interesting finding by Alonso et al. [25
] was the progressive formation of alveolar bone: there appeared to be more bone after 12 months compared to after 6 months in the BMP-2 group. This finding may indicate that evaluation after 4 months, as in the study by Herford et al. [27
], is perhaps too quick to assess the final result of the treatment. If this is true, evaluation at a later stage may show more favourable results.
A specifically interesting subset of patients are skeletally mature patients as these patients showed better results in the BMP-2 group in terms of bone quantity, less complications and less adverse events compared to patients who received cancellous bone of the iliac crest [26
]. Inferior outcome in patients treated with bone grafting after the stage of mixed dentition, i.e. after the eruption of the permanent canines, has been reported previously [28
]. Perhaps, this subset of patients can benefit even more from the application of BMP-2.
It is thought that osteogenesis is a complex process that requires certain combinations of growth factors on specific moments during bone formation. Therefore, it was surprising that the use of just one growth factor in combination with an osteoconductive scaffold led to bone formation. A possible explanation is that BMP-2 stands at or near the top of a cascade of growth factors needed for bone formation and that through biological feedback mechanisms, the right combination of growth factors is attained.
The alveolar bone is a unique bone structure. Besides providing mechanical strength to skeletal system and support for the surrounding soft tissues, the alveolar bone also gives support to teeth and allows tooth eruption, orthodontic movement of teeth into the reconstructed cleft, and, if indicated, osseointegration of dental implants. Unfortunately, quality of bone formation in this respect was not assessed in any of the three studies. Future studies are required to address these issues.