Repair of large saddle defects of the mandibular ridge using dual growth factor release—An experimental pilot study in minipigs

Abstract

Delivery of rhBMP2 from a polymer carrier can improve repair of large saddle defects of the mandibular ridge. Addition of small amounts of rhVEGF can increase bone formation and at the same time reduce the dosage of rhBMP2.

The use of rhBMP2 for augmentation of established horizontal/vertical defects may require additional use of rhVEGF to achieve significant bone regeneration: An in vivo experimental study

“…Another aspect of the histologic findings that is different from other studies is the degradation of the carrier particles. A previous study on these carriers in fresh alveolar ridge defects using the same observation periods had shown an almost complete degradation of the carrier particles between 4 and 13 weeks (Tröltzsch et al, 2017), whereas in the present study carrier particles have exhibited signs of advanced degradation after 13 weeks but clearly visible remnants were still maintained. This again may indicate that established defects provide a reduced metabolic and cellular activity that also is related to the degradation of biomaterial when compared to fresh surgical defects.…”

“…Despite an inconstant positive effect of the addition of rhVEGF, the use of rhBMP2 alone had consistently resulted in a significant enhancement of bone regeneration in all these studies. The carrier used in the present study had also produced a significant enhancement of bone regeneration when used with the same amount growth factors in fresh alveolar ridge defects in the minipig mandible after 13 weeks (Tröltzsch et al, 2017). In contrast to these reports, the results of the present study on established alveolar ridge defects have shown that the use of rhBMP2 alone did not result in a significant enhancement of bone formation at any observation period.…”

“…In fact, preclinical research has shown that the simultaneous delivery of small amounts of rhVEGF together with rhBMP2 can help to reduce the amount of BMP by 50% in repair of mandibular defects in rats (Lohse et al, 2015). This has also been reported for more clinically relevant models in fresh alveolar ridge defects in minipigs (Tröltzsch et al, 2017). Nevertheless, in these defects rhBMP2 still had a positive effect when administered alone.…”

“…The lack of a clear osteoinductive effect of the released rhBMP2 could have been a result of insufficient growth factor delivery from the carrier. The carrier used, however, had been evaluated extensively in previous studies, where it had exhibited a slow release characteristic for rhBMP2 and rhVEGF (Lohse et al, 2015, Schliephake, 2015) and had shown reliable induction of bone formation in rodent models (Lohse et al, 2015, Moser et al, 2017; Moser et al, 2018) and also in alveolar ridge defects in minipigs (Tröltzsch et al, 2017). Thus, it is unlikely, that failure in delivery of osteogenic signals accounted for the lack of biological effect of rhBMP2 in the present study.…”

“…A second precondition would be that there is an established layer of solid bone on the defect surface with little remodelling activity. A previous study in the minipig mandible had shown that after 13 weeks of healing, spontaneous bone regeneration in saddle defects of the same size in minipig mandibles had produced a dense layer of mature bone on the defect surface (Tröltzsch et al, 2017). This corresponded to the clinically appreciable solid layer of bone in the defect area in the present study during the second surgical intervention for augmentation of the established defects.…”