Abstract
The effects of hydroxyapatite (HA)-coating onto collagen carriers for application of recombinant human bone morphogenetic protein 2 (rhBMP-2) on cell differentiation in vitro, and on in vivo healing patterns after sinus-augmentation and alveolar socket-grafting were evaluated. In vitro induction of osteogenic/adipogenic differentiation was compared between the culture media with rhBMP-2 solution and with the released rhBMP-2 from the control collagen and from the HA-coated collagen. Demineralized bovine bone and collagen/HA-coated collagen were grafted with/without rhBMP-2 in sinus-augmentation and tooth-extraction-socket models. Adipogenic induction by rhBMP-2 released from HA-coated collagen was significantly reduced compared to collagen. In the sinus-augmentation model, sites that received rhBMP-2 exhibited large amounts of vascular tissue formation at two weeks and increased adipose tissue formation at eight weeks; this could be significantly reduced by using HA-coated collagen as a carrier for rhBMP-2. In extraction-socket grafting, dimensional reduction of alveolar ridge was significantly decreased at sites received rhBMP-2 compared to control sites, but adipose tissue was increased within the regenerated socket area. In conclusion, HA-coated collagen carrier for Escherichia coli-derived rhBMP-2 (ErhBMP-2) may reduce in vitro induction of adipogenic differentiation and in vivo adipose bone marrow tissue formation in bone tissue engineering by ErhBMP-2.
Highlights
The clinical applications of recombinant human bone morphogenetic protein have been studied widely in bone tissue engineering since the development of protein-recombination technology [1]
Multiple mineralized nodules and lipid vacuoles were observed at all induced sites of the positive control group and both experimental groups with released recombinant human bone morphogenetic protein 2 (rhBMP-2), negative control sites preincubated with standard medium exhibited limited formation of these structures
The area of mineralized nodules and lipid vacuoles was largest at positive control sites preincubated with rhBMP-2 solution, uniformly regardless of the preincubation period (Figure 1)
Summary
The clinical applications of recombinant human bone morphogenetic protein (rhBMP-2) have been studied widely in bone tissue engineering since the development of protein-recombination technology [1]. It was expected that rhBMP-2 would enhance the bone quality in regenerated bone tissue, Kao et al reported decreased bone quality in a histologic study (randomized clinical trial) of sinus augmentation with rhBMP-2 compared to the conventional technique [9]. A recent preclinical study using rabbit sinus model revealed limited formation of mineralized tissue in the central area of the augmentation at sites received bone graft materials accompanied by rhBMP-2 [10]. These findings suggest that instead of promoting the early bone-healing processes within sinus augmentation, rhBMP-2 switched the direction of those processes
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