In vivo evaluation of bone marrow stromal-derived osteoblasts-porous calcium phosphate ceramic composites as bone graft substitute for lumbar intervertebral spinal fusion.
METHODS
Autogenous bone marrow stromal-derived osteoblasts-porous calcium phosphate ceramic composites were constructed in vitro under cell culture for 48 hours and implanted as a bone graft substitute for lumbar intervertebral spinal fusion in rabbits.


OBJECTIVE
To evaluate the efficacy of autogenous bone marrow stromal-derived osteoblasts-porous calcium phosphate ceramic composites as an alternative to autogenous graft materials in a lumbar interbody spinal fusion model.


BACKGROUND
Bone marrow contains a population of rare progenitor cells capable of differentiating into bone, cartilage, muscle, tendon, and other connective tissues. These cells can be induced and differentiated into osteogenic osteoblasts with addition of osteogenic supplements. Combining bone marrow stromal-derived osteoblasts with porous ceramics gave rise to bone tissue in subcutaneous sites and repaired critical size segmental femoral defects. Little work has been done in the spine to assess fusion rates and associated biomechanical characteristics.


METHODS
Five experimental groups were evaluated: sham operation (Group I); porous calcium phosphate ceramics alone (Group II); autogenous tricortical iliac crest (Group III); bone marrow stromal-derived osteoblasts-calcium phosphate ceramic composites (Group IV); bone marrow stromal-derived osteoblasts-calcium phosphate ceramic composites with rhBMP-2 (Group V). All rabbits were killed 12 weeks after surgery, and the spinal fusion segments underwent the evaluation of gross inspection, manual palpation, radiography, computed tomography, nondestructive biomechanical testing, and histologic analysis.


RESULTS
Successful spinal fusion was achieved by manual palpation in 100% (6/6) of animals in Group IV and Group V, 66.7% (4/6) in Group III, 50% (3/6) in Group II, and 0% (0/6) in Group I. Radiographic studies showed that minimal disc height loss was observed with ceramic blocks than with autograft. Biomechanical testingconfirmed that spines from Group IV and Group V were statistically significantly stiffer in flexion, extension, left and right bending, and left and right torsion than Group III and Group II. Histologic analysis demonstrated a qualitative increase of bone formation in fusion mass in Group IV and Group V versus all other groups. The size of fusion mass and the stiffness of fusion segments were greatest in Group V.


CONCLUSIONS
The results indicate that bone marrow stromal-derived osteoblasts-calcium phosphate ceramic composites may provide an alternative to autogenous graft materials for lumbar interbody spinal fusion. Adding recombinant human bone morphogenetic protein-2 into the composites may reinforce the biomechanical stiffness for spinal fusion segments. Porous calcium phosphate ceramics alone were not suitable as a bone graft substitute for lumbar interbody spinal fusion.
Kai
Tang
T
Department of Orthopaedics, Third Hospital of Peking University, Beijing, People's Republic of China. tangkailei@hotmail.com
Shao-qing
Guo
G
Geng-ting
Dang
D
D000818:Animals; D001696:Biomechanical Phenomena; D001854:Bone Marrow Cells / Q000166:cytology; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D018786:Bone Substitutes / Q000008:administration & dosage / Q000494:pharmacology*; D002130:Calcium Phosphates / Q000494:pharmacology*; D002469:Cell Separation; D002478:Cells, Cultured; D002516:Ceramics / Q000494:pharmacology*; D007085:Ilium / Q000637:transplantation; D008161:Lumbosacral Region; D008297:Male; D023421:Models, Animal; D010006:Osteoblasts / Q000166:cytology / Q000637:transplantation*; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology; D011817:Rabbits; D013123:Spinal Fusion / Q000009:adverse effects / Q000379:methods*; D013131:Spine / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000502:physiology; D017154:Stromal Cells / Q000166:cytology; D014057:Tomography, X-Ray Computed; D016212:Transforming Growth Factor beta; D014182:Transplantation, Autologous
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D018786:Bone Substitutes; D002130:Calcium Phosphates; D016212:Transforming Growth Factor beta; C485828:alpha-tricalcium phosphate; C485830:tetracalcium phosphate; C485838:calcium phosphate, monobasic, anhydrous; C020243:calcium phosphate; C485829:calcium phosphate, dibasic, anhydrous