Autogenous bone marrow stromal cell sheets-loaded mPCL/TCP scaffolds induced osteogenesis in a porcine model of spinal interbody fusion.
This study was designed to investigate whether a tissue-engineered construct composed of autogenous cell sheets and a polycaprolactone-based bioresorbable scaffold would enhance bone regeneration and spinal interbody fusion in a large animal model. Porcine-derived autogenous bone marrow stromal cells (BMSCs) cultured into multilayered cell sheets were induced into osteogenic differentiation with dexamethasone, l-ascorbic acid, and β-glycerol phosphate. These cell sheets were assembled with bioresorbable scaffolds made from medical-grade poly(epsilon-caprolactone) incorporating 20% β-tricalcium phosphate (mPCL/TCP) as tissue-engineered BMSC constructs. L2/3, L4/5 discectomies and decortication of the vertebral end plates were performed on 16 SPF Yorkshire pigs through an anterolateral approach. The tissue-engineered BMSC constructs were transplanted into the prepared intervertebral disc spaces of half of the pigs (n = 8), whereas cell-free mPCL/TCP served as controls in the remaining pigs. New bone formation and spinal fusion were evaluated at 3 and 6 months using microcomputed tomography, histology, fluorochrome bone labeling, and biomechanical testing. New bone formation was evident as early as 3 months in the BMSC group. At 6 months, bony fusion was observed in >60% (5/8) of segments in the BMSC group. None of the control animals with cell-free scaffold showed fusion at both time points. Biomechanical evaluation further revealed a significantly increased segmental stability in the BMSC group compared with the cell-free group at 6 months postimplantation (p < 0.01). These findings suggest that mPCL/TCP scaffolds loaded with in vitro differentiated autogenous BMSC sheets could induce bone formation and interbody fusion. This in turn resulted in enhanced segmental stability of the lumbar spine.
Department of Orthopaedic Surgery, National University of Singapore, Singapore, Singapore.
Sunny A
SA
Abbah
Christopher X F
CX
Lam
Kumarsing A
KA
Ramruttun
James C H
JC
Goh
Hee-Kit
HK
Wong
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002130:Calcium Phosphates / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D005453:Fluorescence; D007091:Image Processing, Computer-Assisted; D007403:Intervertebral Disc / Q000000981:diagnostic imaging / Q000187:drug effects; D008022:Ligaments / Q000187:drug effects; D008751:Methylene Blue / Q000378:metabolism; D008954:Models, Biological; D010012:Osteogenesis / Q000187:drug effects*; D011091:Polyesters / Q000494:pharmacology*; D012394:Rosaniline Dyes / Q000378:metabolism; D013123:Spinal Fusion; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D034421:Sus scrofa; D054457:Tissue Scaffolds / Q000737:chemistry; D055114:X-Ray Microtomography
D002130:Calcium Phosphates; D011091:Polyesters; D012394:Rosaniline Dyes; C485817:beta-tricalcium phosphate; C016240:polycaprolactone; C025485:basic fuchsin; D008751:Methylene Blue