Abstract
Although bone morphogenetic protein (BMP) has potent osteoinductivity, the potential adverse events attributed to its burst release prevent its widespread clinical application. Therefore, there is a strong need for BMP delivery systems that maximize osteoinductivity while preventing adverse effects. We evaluated the bone-regenerating potential of NOVOSIS putty (NP), a novel composite combining hydroxyapatite, beta-tricalcium phosphate microsphere/poloxamer 407-based hydrogel, and recombinant human (rh) BMP-2. In vitro assessment of release kinetics by enzyme-linked immunosorbent assay demonstrated sustained release of rhBMP-2 from NP and burst release from collagen sponge (CS), and in vivo assessment of release kinetics by longitudinal tracking of fluorescently labeled rhBMP-2 showed a longer biological half-life of rhBMP-2 with NP than with CS. Furthermore, osteogenic gene expression in MC3T3-E1 cells was significantly higher after co-culture with NP than after co-culture with CS, suggesting that the sustained release of rhBMP-2 from NP effectively contributed to the differentiation of osteoblasts. In a rat spinal fusion model, the volume and quality of newly formed bone was higher in the NP group than in the CS group. Use of NP results in efficient bone regeneration through sustained release of rhBMP-2 and improves the quality of BMP-induced bone.
Highlights
Bone morphogenetic protein (BMP) has potent osteoinductivity, the potential adverse events attributed to its burst release prevent its widespread clinical application
The amounts of recombinant human BMP-2 (rhBMP-2) released from collagen sponge (CS) and NOVOSIS putty (NP) were evaluated by enzyme-linked immunosorbent assay (ELISA) (Fig. 1a)
From days 1 to 7, significantly more rhBMP-2 was released from CS than from NP; CS released most of the rhBMP-2 on day 1, whereas NP released it more gradually
Summary
Bone morphogenetic protein (BMP) has potent osteoinductivity, the potential adverse events attributed to its burst release prevent its widespread clinical application. We evaluated the bone-regenerating potential of NOVOSIS putty (NP), a novel composite combining hydroxyapatite, beta-tricalcium phosphate microsphere/poloxamer 407-based hydrogel, and recombinant human (rh) BMP-2. Among the BMP subtypes, BMP-2 has the most potent osteoinductive capacity, and the US Food and Drug Administration has approved the use of recombinant human BMP-2 (rhBMP-2) with absorbable collagen sponges (CSs) for anterior lumbar interbody fusion[4]. High-dose rhBMP-2 is associated with adverse effects, including inflammation, soft tissue edema, seroma, and unintended ectopic bone formation, which prevent its widespread clinical application[7,8]. We used the rat spinal fusion model to compare the in vivo efficacy of NP and CS as BMP delivery systems
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