title: Fusion performance of low-dose recombinant human bone morphogenetic protein 2 and bone marrow-derived multipotent stromal cells in biodegradable scaffolds: a comparative study in a large animal model of anterior lumbar interbody fusion.
abstract: METHODS
  A large animal study comparing interbody fusion of a bioresorbable scaffold loaded with either low-dose recombinant human bone morphogenetic protein 2 (rhBMP-2) or bone marrow-derived multipotent stromal cells (BMSCs).
  
  
  OBJECTIVE
  To compare the quality of fusion resulting from implantation of medical grade poly (ε-caprolactone)-20% tricalcium phosphate (mPCL/TCP) scaffolds and two different bone growth stimulating agents.
  
  
  BACKGROUND
  Nondegradable cages have been used for interbody fusion with good results. However, the overall advantage of lifelong implantation of a nondegradable device remains a subject of ongoing debate. The use of bioresorbable scaffolds might offer superior alternatives. In this study, we evaluated the quality of fusion obtained with two potential bone graft substitutes.
  
  
  METHODS
  Eleven Yorkshire pigs underwent a bisegmental (L2/L3; L4/L5) anterior lumbar interbody fusion (ALIF) in four groups, namely: (1) mPCL/TCP + 0.6 mg rhBMP-2; (2) mPCL/TCP + BMSCs; (3) mPCL/TCP (negative control); and (4) autologous bone grafts (positive control). RESULTS. The mean radiographic scores at 9 months were 3.0, 1.7, 1.0, and 1.8 for groups 1 to 4, respectively. The bone volume fraction of group 1 was two-folds higher than group 2. Histology, micro-computed tomographic scanning and biomechanical evaluation demonstrated solid and comparable fusion between groups 1 and 4. However, group 2 showed inferior quality of fusion when compared with groups 1 and 4 while group 3 showed no fusion even at 9 months. In addition, there was no evidence of implant rejection, chronic inflammation or any other complications.
  
  
  CONCLUSIONS
  mPCL/TCP scaffolds loaded with low-dose rhBMP-2 is comparable to autograft bone as a bone graft substitute in this large animal ALIF model. Although BMSCs lagged behind autograft bone and rhBMP-2, evidence of bone ingrowth in this group warrants further investigation. Our results suggest that mPCL/TCP scaffolds loaded with rhBMP-2 or BMSCs may be a viable alternative to conventional cages and autograft bone.
authors.affiliation: Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore.
authors.forename: Sunny A
authors.initials: SA
authors.lastname: Abbah
authors.forename: Christopher X F
authors.initials: CX
authors.lastname: Lam
authors.forename: Amit K
authors.initials: AK
authors.lastname: Ramruttun
authors.forename: James C H
authors.initials: JC
authors.lastname: Goh
authors.forename: Hee-Kit
authors.initials: HK
authors.lastname: Wong
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D001696:Biomechanical Phenomena; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage*; D002130:Calcium Phosphates / Q000737:chemistry; D002478:Cells, Cultured; D006801:Humans; D007085:Ilium / Q000637:transplantation; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology / Q000601:surgery*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D023421:Models, Animal; D039902:Multipotent Stem Cells / Q000637:transplantation*; D016348:Osseointegration / Q000187:drug effects*; D011091:Polyesters / Q000737:chemistry; D016059:Range of Motion, Articular; D011994:Recombinant Proteins / Q000008:administration & dosage; D013123:Spinal Fusion / Q000379:methods*; D013552:Swine; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D014182:Transplantation, Autologous; D055114:X-Ray Microtomography
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D002130:Calcium Phosphates; D011091:Polyesters; D011994:Recombinant Proteins; C016240:polycaprolactone; C018392:tricalcium phosphate