In vivo validation of osteoinductivity and biocompatibility of BMP-2 enriched calcium phosphate cement alongside retrospective description of its clinical adverse events.

Abstract

Purpose: Although bone morphogenetic protein-2 (BMP-2) possesses potent osteoinductivity, there have been some concerns on the safety of BMP-2 and BMP-2-incorporated bone substitutes used for bone formation. On the other hand, BMP-2-loaded calcium phosphate cement (BMP-2@CPC) has been developed and used for bone regeneration in oral implantology. Therefore, this study aims to investigate this product's biocompatibility and clinical safety after being used in maxillofacial surgery.

Materials and methods: A rat model was employed to assess the osteoinduction and biocompatibility of BMP-2@CPC. Further, a retrospective investigation was carried out: 110 patients who received BMP-2@CPC treatment after their maxillofacial surgery were recruited to describe relative adverse events.

Results: In vivo, BMP-2@CPC showed a significantly higher mean bone volume density and osteoblasts volume density (15 ± 2% and 3 ± 1%)than those of the CPC group (p < 0.05) after being implanted in the dorsal area of rats. Regarding biocompatibility, the mean fibrous tissue volume density was significantly lower in the BMP-2@CPC group (20 ± 5% compared to 31 ± 6%, p = 0.026). The retrospective clinical study showed that only five mild/moderate adverse events were identified in four patients based on the medical records of 110 patients, including swelling, bony mass, and wound dehiscence. This adverse event occurrence was not affected by gender, age, the dose of filled materials, and operations in the study (p > 0.05).

Conclusions: BMP-2-loaded CPC has osteoinductivity and more promising biocompatibility than pure CPC. However, its degradation is slower than CPC. The safety of BMP-2-loaded CPC with 0.5 or 1 mg BMP-2 is promising in oral maxillofacial surgery.

Clinical implications: This study confirmed the promising safety of this BMP-2 incorporated CPC used in dental clinical practice, which can promote its reassuring application for dental implant placement in bone insufficient areas.