Effect of Escherichia coli-produced recombinant human bone morphogenetic protein 2 on the regeneration of canine segmental ulnar defects

Abstract

Because bone morphogenetic protein 2 gene transfected Escherichia coli (E-BMP-2) produce recombinant human BMP-2 (rhBMP-2) more efficiently than mammalian cells (Chinese hamster ovary [CHO]-BMP-2), they may be a more cost-effective source of rhBMP-2 for clinical use. However, use of E-BMP-2 for regenerating long bones in large animals has not been reported. In the current study, we evaluated the healing efficacy of E-BMP-2 in a canine model. We created 2.5-cm critical-size segmental ulnar defects in test animals, then implanted E-BMP-2 and 700 mg of artificial bone (beta-tricalcium phosphate; β-TCP) into the wounds. We examined the differential effects of 5 E-BMP-2 treatments (0, 35, 140, 560, and 2240 μg) across 5 experimental groups (control, BMP35, BMP140, BMP560, and BMP2240). Radiography and computed tomography were used to observe the regeneration process. The groups in which higher doses of E-BMP-2 were administered (BMP560 and BMP2240) displayed more pronounced bone regeneration; the regenerated tissues connected to the host bone, and the cross-sectional areas of the regenerated bone were larger than those of the originals. The groups in which lower doses of E-BMP-2 were administered (BMP35 and BMP140) experienced relatively less bone regeneration; furthermore, the regenerated tissues failed to connect to the host bone. In these groups, the cross-sectional areas of the regenerated bone were equal to or smaller than those of the originals. No regeneration was observed in the control group. These findings suggest that, like CHO-BMP-2, E-BMP-2 can be used for the regeneration of large defects in long bones and that its clinical use might decrease the cost of bone regeneration treatments.

Comparative Study of Chinese Hamster Ovary Cell Versus Escherichia coli‐Derived Bone Morphogenetic Protein‐2 Using the Critical‐Size Supraalveolar Peri‐Implant Defect Model

“…CHO cell‐ and E. coli‐ derived rhBMP‐2 have been shown to induce comparable dose‐dependent ectopic bone formation after intramuscular implantation in rodent screening models, suggesting E. coli ‐derived rhBMP‐2 to be a realistic alternative to CHO cell‐derived rhBMP‐2 26,27 . Nevertheless, the efficacy of E. coli ‐derived rhBMP‐2 in large‐animal, orthotopic, clinically relevant settings has received limited attention 28,29 . Therefore, the objective of this study is to evaluate local bone formation and dental implant osseointegration in conjunction with alveolar augmentation using E. coli ‐derived rhBMP‐2 and compare to the benchmark CHO cell‐derived rhBMP‐2 using an established large‐animal model.…”

“…26,27 Nevertheless, the efficacy of E. coli-derived rhBMP-2 in large-animal, orthotopic, clinically relevant settings has received limited attention. 28,29 Therefore, the objective of this study is to evaluate local bone formation and dental implant osseointegration in conjunction with alveolar augmentation using E. coliderived rhBMP-2 and compare to the benchmark CHO cell-derived rhBMP-2 using an established large-animal model.…”

Bone morphogenetic protein-2 and bone therapy: successes and pitfalls

“…[17] The production of recombinant BMP-2 from Escherichia coli (eBMP-2) has facilitated production of large quantities of the protein at a relatively lower cost. [23] Pitfalls Many benefits are associated with the use of rhBMP-2, but it is not free of complications, as summarised in Table 2. Studies show they are safe when used for 'on-label' conditions, but risks develop when used for 'off-label' conditions.…”

“…[41] Another study explored the use of Escherichia coli produced rhBMP-2 in canines, as E. coli produced rhBMP-2 more efficiently than mammalian cells. [23] This study focused on the healing efficacy of this particular type of BMP-2 and found that the concentration of BMP-2 delivered affected the healing efficacy, with higher concentrations displaying more osteogenesis and a more pronounced bone regeneration. [23] Using E. coli-derived BMP-2 (eBMP-2) may be more cost-effective and efficient as a source of rhBMP-2 for clinical use.…”

“…[23] This study focused on the healing efficacy of this particular type of BMP-2 and found that the concentration of BMP-2 delivered affected the healing efficacy, with higher concentrations displaying more osteogenesis and a more pronounced bone regeneration. [23] Using E. coli-derived BMP-2 (eBMP-2) may be more cost-effective and efficient as a source of rhBMP-2 for clinical use. [5] This study made promising steps towards future studies that investigate a range of uses that eBMP-2 may have in veterinary medicine and perhaps even in humans.…”