Effects of rhBMP‑2‑loaded hydroxyapatite granules/beta‑tricalcium phosphate hydrogel (HA/β‑TCP/hydrogel) composite on a rat model of caudal intervertebral fusion

概要

〔目的(Purpose)〕
Off-label use of recombinant human bone morphogenetic protein (BMP)-2 for posterior lumbar interbody fusion is prevalent though there exist controversies on the effects and the inflammation-related side effects. One of the potential causes for these inconsistent results is the uncontrolled release of BMP-
2 from collagen carrier. The purpose of this study was to elucidate the effects of a novel carrier (hydroxyapatite [HA] / 0-tricalcium phosphate [TCP] microsphere/hydrogel) as a carrier for rhBMP-2 in bone formation and to compare the adverse events of HA/0-TCP/hydrogel with those of a collagen sponge (CS) carrier using a rat caudal intervertebral fusion model.

〔方法ならびに成績(Methods/Results))
Methods; Forty male rats were treated with coccygeal intervertebral fusion and were divided into the following five groups based on the grafting material (allogenic iliac bone only [IB group]. collagen
sponge soaked with BMP-2 [CS group]. and HA/6-TCP/hydrogel containing BMP-2 [Novosis putty: NP group] and CS group and NP group were subdivided by BMP dosage (3ug [low BMP] or 10pg [high BMP]) (n=8 for each group).

Results; Fusion rate, incidence of adverse events (soft tissue swelling, delayed wound healing, osteolysis, and ectopic bone formation), the adverse event score (AES), and the swelling ratio of surgical site at the intervertebral disc space were evaluated. Fusion rates of both NP groups (low and
high BMP) were higher than that of IB group (p=0. 04), but those of both CS groups (low and high BMP) were not different from that of the IB group. Furthermore, the incidence of ectopic bone formation, soft tissue swelling and the AES were significantly lower in the NP-high BMP group compared to the CS-high BMP group.

(総 括(Conclusion)〕
The HA/0-TCP/hydroge1 composite enabled superior bone induction with a low dose of BMP-2 and reduced the incidence of side effects caused by high doses of BMP-2 compared with the collagen carrier in a rat model of caudal intervertebral fusion. The HA//3-TCP/hydrogel composite is a novel biomaterial for efficient bone regeneration using BMP-2.