title: Evaluation of posterolateral lumbar fusion in sheep using mineral scaffolds seeded with cultured bone marrow cells.
abstract: The objective of this study is to investigate the efficacy of hybrid constructs in comparison to bone grafts (autograft and allograft) for posterolateral lumbar fusion (PLF) in sheep, instrumented with transpedicular screws and bars. Hybrid constructs using cultured bone marrow (BM) mesenchymal stem cells (MSCs) have shown promising results in several bone healing models. In particular, hybrid constructs made by calcium phosphate-enriched cells have had similar fusion rates to bone autografts in posterolateral lumbar fusion in sheep. In our study, four experimental spinal fusions in two animal groups were compared in sheep: autograft and allograft (reference group), hydroxyapatite scaffold, and hydroxyapatite scaffold seeded with cultured and osteoinduced bone marrow MSCs (hybrid construct). During the last three days of culture, dexamethasone (dex) and beta-glycerophosphate (β-GP) were added to potentiate osteoinduction. The two experimental situations of each group were tested in the same spinal segment (L4-L5). Spinal fusion and bone formation were studied by clinical observation, X-ray, computed tomography (CT), histology, and histomorphometry. Lumbar fusion rates assessed by CT scan and histology were higher for autograft and allograft (70%) than for mineral scaffold alone (22%) and hybrid constructs (35%). The quantity of new bone formation was also higher for the reference group, quite similar in both (autograft and allograft). Although the hybrid scaffold group had a better fusion rate than the non-hybrid scaffold group, the histological analysis revealed no significant differences between them in terms of quantity of bone formation. The histology results suggested that mineral scaffolds were partly resorbed in an early phase, and included in callus tissues. Far from the callus area the hydroxyapatite alone did not generate bone around it, but the hybrid scaffold did. In nude mice, labeled cells were induced to differentiate in vivo and monitored by bioluminescence imaging (BLI). Although the cultured MSCs had osteogenic potential, their contribution to spinal fusion when seeded in mineral scaffolds, in the conditions disclosed here, remains uncertain probably due to callus interference with the scaffolds. At present, bone autografts are better than hybrid constructs for posterolateral lumbar fusion, but we should continue to seek better conditions for efficient tissue engineering.
authors.affiliation: Laboratory of Bioengineering and Tissue Regeneration (LABRET), Department of Cell Biology, Genetics and Physiology, Faculty of Sciences, University of Málaga, Campus de Teatinos, Málaga 29071, Spain. lolincuenca@hotmail.com.
authors.forename: María D
authors.initials: MD
authors.lastname: Cuenca-López
authors.affiliation: Laboratory of Bioengineering and Tissue Regeneration (LABRET), Department of Cell Biology, Genetics and Physiology, Faculty of Sciences, University of Málaga, Campus de Teatinos, Málaga 29071, Spain. andrades@uma.es.
authors.forename: José A
authors.initials: JA
authors.lastname: Andrades
authors.affiliation: Department of Pathological Anatomy, Faculty of Medicine, University of Cádiz, Cádiz 11003, Spain. santiago.gomez@uca.es.
authors.forename: Santiago
authors.initials: S
authors.lastname: Gómez
authors.affiliation: Networking Biomedical Research Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid 28029, Spain. plazamora@gmail.com.
authors.forename: Plácido
authors.initials: P
authors.lastname: Zamora-Navas
authors.affiliation: Networking Biomedical Research Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid 28029, Spain. eguerado@hcs.es.
authors.forename: Enrique
authors.initials: E
authors.lastname: Guerado
authors.affiliation: Networking Biomedical Research Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid 28029, Spain. nrvnqb@cid.csic.es.
authors.forename: Nuria
authors.initials: N
authors.lastname: Rubio
authors.affiliation: Networking Biomedical Research Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid 28029, Spain. jeronimo.blanco@iqac.csic.es.
authors.forename: Jerónimo
authors.initials: J
authors.lastname: Blanco
authors.affiliation: Laboratory of Bioengineering and Tissue Regeneration (LABRET), Department of Cell Biology, Genetics and Physiology, Faculty of Sciences, University of Málaga, Campus de Teatinos, Málaga 29071, Spain. jeronimo.blanco@iqac.csic.es.
authors.forename: José
authors.initials: J
authors.lastname: Becerra
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation; D005260:Female; D008163:Luminescent Measurements; D051379:Mice; D008819:Mice, Nude; D008903:Minerals / Q000737:chemistry; D057054:Molecular Imaging; D010012:Osteogenesis; D012756:Sheep; D013123:Spinal Fusion / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry; D014057:Tomography, X-Ray Computed
chemical_list: D008903:Minerals