A cell-based combination product for the repair of large bone defects.

Abstract

Regenerative cell-based implants using periosteum-derived stem cells were developed for the treatment of large 3cm fresh and 4.5centimeter biological compromised bone gaps in a tibial sheep model and compared with an acellular ceramic-collagen void filler. It was hypothesized that the latter is insufficient to heal large skeletal defects due to reduced endogenous biological potency. To this purpose a comparison was made between the ceramic dicalciumphosphate scaffold (CopiOs®) as such, the same ceramic coated with clinical grade Bone Morphogenetic Protein 2 and 6 (BMP) only or a BMP coated cell-seeded combination product. These implants were evaluated in 2 sheep models, a fresh 3cm critical size tibial defect and a 4.5cm biologically exhausted tibial defect. For the groups in which growth factors were applied, BMP-6 was chosen at a dose of 344μg for 3cm and 1.500μg or 3.800μg for 4.5cm defects. An additional group in the 4.5cm defect was tested using BMP-2 in a dose of 1.500μg. For all the cell based implants autologous periosteum-derived cells were used which were cultured in monolayer during 6weeks. For the fresh defect 408 million cells and for the biologically exhausted tibial defect 612 million cells were drop-seeded on the BMP coated scaffolds. Bone healing was studied during 16weeks postimplantation, using standard radiographs. While fresh defects responded to all treatments, regardless the use of cells, the biologically hampered defects responded in half of the cases and only if the BMP-cell combination product was used, supporting the concept that cell-based therapies may become attractive in treating defects with a compromised biological status.