title: Healing of an ulnar defect using a proprietary TCP bone graft substitute, JAX, in association with autologous osteogenic cells and growth factors.
abstract: Currently, available synthetic bone substitutes have adequate osteoconductive properties but have little or no osteoinductivity. Recent research has focused on using osteogenic growth factors or cells to provide this. JAX is a beta tricalcium phosphate bone graft substitute that has a novel shape and interlocking design. This study investigated delivery methods and the use of autologous cell therapy to enhance healing of a bone defect using JAX as a scaffold. Bone marrow was harvested from 24 New Zealand White rabbits. The mononuclear cell fraction was isolated and culture expanded. Bilateral 1.5 cm defects in the ulna were filled with: Group 1: JAX alone, Group 2: JAX plus 1x10(7) autologous BMSCs injected at the time of surgery, Group 3: JAX plus 8x10(6) autologous BMSCs cultured on granules for 14 days prior to surgery, Group 4: JAX plus fresh bone marrow (BMA), Group 5: cortical autograft, Group 6: JAX plus 2.5 microg VEGF. Radiographs demonstrated that there was more new bone in the BMA and VEGF groups compared to JAX alone. Groups containing autologous BMSCs were only slightly better than JAX alone in the amount of bone in the defect but did improve bridging of the osteotomy. Histomorphometry identified a significant increase in bone volume in the BMA group compared to JAX alone. BMA and VEGF enhanced healing of bone defects whereas expanded BMSCs provided little advantage over scaffold alone. There was no difference between delivery methods of autologous BMSCs. These observations suggest that the provision of osteogenic cells alone is insufficient to enhance bone healing and that additional factors are required to initiate this process in vivo.
authors.affiliation: Trauma Research Group, Queen's University Belfast, Musgrave Park Hospital, Belfast, BT9 7JB, UK. s.a.clarke@qub.ac.uk
authors.forename: S A
authors.initials: SA
authors.lastname: Clarke
authors.forename: N L
authors.initials: NL
authors.lastname: Hoskins
authors.forename: G R
authors.initials: GR
authors.lastname: Jordan
authors.forename: D R
authors.initials: DR
authors.lastname: Marsh
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D018786:Bone Substitutes / Q000627:therapeutic use*; D002130:Calcium Phosphates / Q000627:therapeutic use*; D017102:Fracture Healing / Q000187:drug effects; D008297:Male; D008855:Microscopy, Electron, Scanning; D010012:Osteogenesis; D011817:Rabbits; D011859:Radiography; D017154:Stromal Cells / Q000637:transplantation; D014182:Transplantation, Autologous; D014458:Ulna Fractures / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D042461:Vascular Endothelial Growth Factor A / Q000627:therapeutic use
chemical_list: D018786:Bone Substitutes; D002130:Calcium Phosphates; D042461:Vascular Endothelial Growth Factor A; C485817:beta-tricalcium phosphate