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Site-Directed Immobilization of Bone Morphogenetic Protein 2 to Solid Surfaces by Click Chemistry
Published on: March 29, 2018
Comparative osteogenic performance of Chinese hamster ovary cell-derived versus Escherichia coli-derived recombinant
Charles Matthews1, Lyndsey Johnson1, Whitney Holden1
1Locate Bio Ltd, Beeston, UK.
Aims:
Recombinant human bone morphogenetic protein-2 (rhBMP-2) is used clinically for bone regeneration. The Food and Drug Administration-approved clinical product (Infuse) is Chinese hamster ovary (CHO)-derived, but Escherichia coli (EC)-derived rhBMP-2 may offer manufacturing advantages. This study compared CHO- and EC-derived rhBMP-2 potency in vitro and in vivo.
Methods:
Four EC-derived rhBMP-2 preparations were screened using alkaline phosphatase (ALP) assays in C2C12 and W20-17 cells. The most potent (EC-MAX) was compared to CHO-rhBMP-2. A total of 15 male athymic rats received bilateral absorbable collagen sponge (ACS) implants loaded with 17 µg rhBMP-2 (CHO or EC-MAX) in muscle pouches for four weeks. Bone formation was assessed by radiography, micro-CT, and histology.
Results:
EC-MAX showed 2.2-fold higher osteogenic activity in W20-17 cells and 1.3-fold in C2C12 cells versus CHO-rhBMP-2. In vivo, EC-MAX produced ~ ten-fold greater bone volume (88.5 mm³ (SD 12.8) vs 9.2 mm³ (SD 5.4)) and tissue volume (203.3 mm³ (SD 47.9) vs 15.0 mm³ (SD 8.8)). Histology confirmed more mature bone architecture in EC-MAX implants with adipocyte-filled marrow spaces.
Conclusion:
Potency cannot be generalized across products. Inter-supplier potency variation exists among EC-derived rhBMP-2 products. EC-MAX demonstrated superior osteoinductive potential both in vitro and in vivo versus CHO. However, substantial variability highlights the need for product-specific characterization.
